Primary immunodeficiencies are disorders in which part of the body's immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 is missing or does not function properly. To be considered a primary immunodeficiency

Immunodeficiency

Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...

, the cause of the immune deficiency must not be secondary in nature (i.e., caused by other disease, drug treatment, or environmental exposure to toxins). Most primary immunodeficiencies are genetic disorder

Genetic disorder

A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....

s; the majority are diagnosed in child

Child

Biologically, a child is generally a human between the stages of birth and puberty. Some vernacular definitions of a child include the fetus, as being an unborn child. The legal definition of "child" generally refers to a minor, otherwise known as a person younger than the age of majority...

ren under the age of one, although milder forms may not be recognized until adulthood. About 1 in 500 people is born with a primary immunodeficiency.

Signs and symptoms

The precise symptoms of a primary immunodeficiency depend on the type of defect. Generally, the symptoms and signs that lead to the diagnosis of an immunodeficiency include recurrent or persistent infection

Infection

An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

s or developmental delay

Developmental disability

Developmental disability is a term used in the United States and Canada to describe lifelong disabilities attributable to mental or physical impairments, manifested prior to age 18. It is not synonymous with "developmental delay" which is often a consequence of a temporary illness or trauma during...

 as a result of infection. Particular organ problems (e.g. diseases involving the skin

Skin

-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...

, heart

Heart

The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

, facial development and skeletal system) may be present in certain conditions. Others predispose to autoimmune disease

Autoimmune disease

Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...

, where the immune system attacks the body's own tissues, or tumours (sometimes specific forms of cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, such as lymphoma

Lymphoma

Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

). The nature of the infections, as well as the additional features, may provide clues as to the exact nature of the immune defect.

Diagnosis

The basic tests performed when an immunodeficiency is suspected should include a full blood count (including accurate lymphocyte

Lymphocyte

A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...

 and granulocyte

Granulocyte

Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...

 counts) and immunoglobulin levels (the three most important types of antibodies: IgG

Immunoglobulin G

Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...

, IgA

Immunoglobulin A

Immunoglobulin A is an antibody that plays a critical role in mucosal immunity. More IgA is produced in mucosal linings than all other types of antibody combined; between three and five grams are secreted into the intestinal lumen each day....

 and IgM

Immunoglobulin M

Immunoglobulin M, or IgM for short, is a basic antibody that is produced by B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system...

).

Other tests are performed depending on the suspected disorder:

• Quantification of the different types of mononuclear cells in the blood (i.e. lymphocytes and monocyte
  Monocyte
  Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...
  
  s): different groups of T lymphocytes
  T cell
  T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
  
   (dependent on their cell surface markers, e.g. CD4+
  CD4
  CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
  
  , CD8+
  CD8
  CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
  
  , CD3+, TCRαβ and TCRγδ), groups of B lymphocytes
  B cell
  B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...
  
   (CD19, CD20, CD21 and Immunoglobulin), natural killer cell
  Natural killer cell
  Natural killer cells are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses...
  
  s and monocytes (CD15+), as well as activation markers (HLA-DR, CD25
  CD25
  CD25 is the alpha chain of the IL-2 receptor. It is a type I transmembrane protein present on activated T cells, activated B cells, some thymocytes, myeloid precursors, and oligodendrocytes that associates with CD122 to form a heterodimer that can act as a high-affinity receptor for IL-2.CD25 is...
  
  , CD80
  CD80
  Cluster of Differentiation 80 is a protein found on activated B cells and monocytes that provides a costimulatory signal necessary for T cell activation and survival...
  
   (B cells).
• Tests for T cell function: skin tests for delayed-type hypersensitivity
  Cell-mediated immunity
  Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
  
  , cell responses to mitogen
  Mitogen
  A mitogen is a chemical substance that encourages a cell to commence cell division, triggering mitosis. A mitogen is usually some form of a protein.Mitogenesis is the induction of mitosis, typically via a mitogen....
  
  s and allogeneic cells, cytokine
  Cytokine
  Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
  
   production by cells
• Tests for B cell function: antibodies to routine immunisations and commonly acquired infections, quantification of IgG subclasses
• Tests for phagocyte
  Phagocyte
  Phagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
  
   function: reduction of nitro blue tetrazolium chloride
  Nitro blue tetrazolium chloride
  Nitro blue tetrazolium is a chemical compound composed of two tetrazole moieties. It is used in immunology for sensitive detection of alkaline phosphatase . NBT serves as the oxidant and BCIP is the AP-substrate ....
  
  , assays of chemotaxis
  Chemotaxis
  Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
  
  , bactericidal activity.

Due to the rarity of many primary immunodeficiencies, many of the above tests are highly specialised and tend to be performed in research laboratories.

Criteria for diagnosis were agreed in 1999. For instance, an antibody deficiency can be diagnosed in the presence of low immunoglobulins, recurrent infections and failure of the development of antibodies on exposure to antigens. The 1999 criteria also distinguish between "definitive", "probable" and "possible" in the diagnosis of primary immunodeficiency. "Definitive" diagnosis is made when it is likely that in 20 years, the patient has a >98% chance of the same diagnosis being made; this level of diagnosis is achievable with the detection of a genetic mutation or very specific circumstantial abnormalities. "Probable" diagnosis is made when no genetic diagnosis can be made, but the patient has all other characteristics of a particular disease; the chance of the same diagnosis being made 20 years later is estimated to be 85-97%. Finally, a "possible" diagnosis is made when the patient has only some of the characteristics of a disease are present, but not all.

Conditions

The International Union of Immunological Societies

International Union of Immunological Societies

The International Union of Immunological Societies, a member of the International Council for Science, is an organization which serves as an umbrella organization for many national immunological societies. The organization was founded in 1969....

 recognises eight classes of primary immunodeficiencies, totaling over 120 conditions. Their most recent update retained the classification into eight groups, while adding several new conditions into these groups (such as coronin-1A deficiency, immunodeficiency with centromeric instability and facial anomalies, and defects of Ficolin 3).

Table I: Combined T and B–cell immunodeficiencies

In these disorders both T lymphocytes

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

 and often B lymphocytes

B cell

B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

, regulators of adaptive immunity, are dysfunctional or decreased in number. The main members are various types of severe combined immunodeficiency

Severe combined immunodeficiency

Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...

 (SCID).

1. T-/B+ SCID (T cells predominantly absent): γc deficiency, JAK3 deficiency, interleukin 7
   Interleukin 7
   IL-7 a hematopoietic growth factor secreted by stromal cells in the red marrow and thymus. It is also produced by keratinocytes, dendritic cells, hepatocytes, neurons, and epithelial cells but is not produced by lymphocytes.- Genetics :...
   
    receptor chain α deficiency, CD45
   CD45
   Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. PTPRC is also known as CD45 antigen , which was originally called leukocyte common antigen.- Function :The protein encoded by this gene is a member of the protein tyrosine...
   
    deficiency, CD3δ/CD3ε deficiency.
2. T-/B- SCID (both T and B cells absent): RAG 1/2
   Recombination activating gene
   The recombination activating genes encode enzymes that play an important role in the rearrangement and recombination of the genes of immunoglobulin and T cell receptor molecules during the process of VDJ recombination...
   
    deficiency, DCLRE1C
   DCLRE1C
   Protein artemis is a protein that in humans is encoded by the DCLRE1C gene.- Function :This gene encodes a nuclear protein that is involved in VJ recombination and DNA repair...
   
    deficiency, adenosine deaminase
   Adenosine deaminase
   Adenosine deaminase is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.-Reactions:...
   
    (ADA) deficiency, reticular dysgenesis
3. Omenn syndrome
   Omenn syndrome
   Omenn syndrome is an autosomal recessive severe combined immunodeficiency associated with mutations in the recombination activating genes , affecting circulating levels of both B-cells and T-cells.-Symptoms:...
   
   
4. DNA ligase
   DNA ligase
   In molecular biology, DNA ligase is a specific type of enzyme, a ligase, that repairs single-stranded discontinuities in double stranded DNA molecules, in simple words strands that have double-strand break . Purified DNA ligase is used in gene cloning to join DNA molecules together...
   
    type IV deficiency
5. Cernunnos deficiency
6. CD40 ligand
   CD154
   CD154, also called CD40 ligand or CD40L, is a protein that is primarily expressed on activated T cells and is a member of the TNF superfamily of molecules. It binds to CD40 on antigen-presenting cells , which leads to many effects depending on the target cell type...
   
    deficiency
7. CD40
   CD40 (protein)
   CD40 is a costimulatory protein found on antigen presenting cells and is required for their activation. The binding of CD154 on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects....
   
    deficiency
8. Purine nucleoside phosphorylase (PNP) deficiency
   Purine nucleoside phosphorylase deficiency
   Purine nucleoside phosphorylase deficiency, often called PNP-deficiency, is a rare autosomal recessive metabolic disorder which results in severe combined immunodeficiency.-Signs and symptoms:...
   
   
9. CD3γ deficiency
10. CD8
    CD8
    CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
    
     deficiency
11. ZAP-70
    ZAP-70
    ZAP-70 is an abbreviation for Zeta-chain-associated protein kinase 70 . The protein is a member in the protein-tyrosine kinase family...
    
     deficiency
12. Ca++ channel deficiency
13. MHC class I
    MHC class I
    MHC class I molecules are one of two primary classes of major histocompatibility complex molecules and are found on every nucleated cell of the body...
    
     deficiency
14. MHC class II
    MHC class II
    MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....
    
     deficiency
15. Winged helix deficiency
16. CD25 deficiency
17. STAT5b deficiency
18. Itk deficiency
19. DOCK8 deficiency

Table II: Predominantly antibody deficiencies

In primary antibody deficiencies

Humoral immune deficiency

Humoral immune deficiencies are conditions which cause impairment of humoral immunity, which can lead to immunodeficiency. It can be mediated by insufficient number or function of B cells, the plasma cells they differentiate into , or the antibody secreted by the plasma cells.They are associated...

, one or more isotypes of immunoglobulin are decreased or don't function properly. These proteins, generated by plasma cell

Plasma cell

Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...

s, normally bind to pathogens, targeting them for destruction.

1. Absent B cells with a resultant severe reduction of all types of antibody: X-linked agammaglobulinemia
   X-linked agammaglobulinemia
   X-linked agammaglobulinemia is a rare X-linked genetic disorder that was discovered in 1952 which affects the body's ability to fight infection. XLA is an X-linked disorder, and therefore is more common in males...
   
    (btk
   Bruton's tyrosine kinase
   Bruton's tyrosine kinase is a type of kinase enzyme implicated in the primary immunodeficiency disease X-linked agammaglobulinemia . Its exact mechanism of action remains unknown, but it plays a crucial role in B cell maturation as well as mast cell activation through the high-affinity IgE receptor...
   
    deficiency, or Bruton
   Ogden Bruton
   Ogden Carr Bruton was a pediatrician and chief of pediatrics at Walter Reed Army Hospital, where he organized the first pediatric residency at this hospital...
   
   's agammaglobulinemia), μ
   Immunoglobulin M
   Immunoglobulin M, or IgM for short, is a basic antibody that is produced by B cells. It is the primary antibody against A and B antigens on red blood cells. IgM is by far the physically largest antibody in the human circulatory system...
   
   -Heavy chain
   Heavy chain
   ]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...
   
    deficiency, l 5
   Immunoglobulin light chain
   ]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...
   
    deficiency, Igα
   CD79
   CD79 is a transmembrane protein that forms a complex with the B-cell receptor and generates a signal following recognition of antigen by the BCR...
   
    deficiency, BLNK deficiency, thymoma with immunodeficiency
   Thymoma with immunodeficiency
   Thymoma with immunodeficiency is a condition that occurs in adults in whom hypogammaglobulinemia, deficient cell-mediated immunity, and benign thymoma may develop almost simultaneously....
   
   
2. B cells low but present or normal, but with reduction in 2 or more isotypes (usually IgG & IgA, sometimes IgM): common variable immunodeficiency
   Common variable immunodeficiency
   Common variable immunodeficiency is a group of approximately 150 primary immunodeficiencies , which have a common set of symptoms but which have different underlying causes.Common variable immunodeficiency is the most commonly encountered primary immunodeficiency.-Causes and types:CVID...
   
    (CVID), ICOS deficiency, CD19
   CD19
   B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...
   
    deficiency, TACI
   Tumor necrosis factor receptor
   A tumor necrosis factor receptor , or death receptor, is a trimeric cytokine receptor that binds tumor necrosis factors . The receptor cooperates with an adaptor protein , which is important in determining the outcome of the response A tumor necrosis factor receptor (TNFR), or death receptor, is a...
   
    (TNFRSF13B) deficiency, BAFF receptor
   B-cell activating factor
   B-cell activating factor also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFLSF13B gene...
   
    deficiency.
3. Normal numbers of B cells with decreased IgG and IgA
   IGA
   Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
   
    and increased IgM
   IGM
   IGM as an acronym or abbreviation can refer to:* Immunoglobulin M , the primary antibody against A and B antigens on red blood cells* International Grandmaster, a chess ranking* intergalactic medium* Intragroup medium - see: Intracluster medium...
   
   : Hyper-IgM syndromes
4. Normal numbers of B cells with isotype or light chain deficiencies: heavy chain
   Heavy chain
   ]The immunoglobulin heavy chain is the large polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains. Several different types of heavy chain exist that define the class or isotype of an antibody. These heavy chain types vary...
   
    deletions, kappa chain
   Immunoglobulin light chain
   ]The immunoglobulin light chain is the small polypeptide subunit of an antibody .A typical antibody is composed of two immunoglobulin heavy chains and two Ig light chains.-In humans:...
   
    deficiency, isolated IgG subclass deficiency, IgA with IgG subsclass deficiency, selective immunoglobulin A deficiency
   Selective immunoglobulin A deficiency
   Selective immunoglobulin A deficiency is a relatively mild genetic immunodeficiency. People with this deficiency lack immunoglobulin A , a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract. It is defined as an undetectable...
   
   
5. Specific antibody deficiency to specific antigens with normal B cell and normal Ig concentrations
6. Transient hypogammaglobulinemia of infancy
   Transient hypogammaglobulinemia of infancy
   Transient hypogammaglobulinemia of infancy is a form of hypogammaglobulinemia appearing after birth, leading to a reduction in the level of IgG, and also sometimes IgA and IgM...
   
    (THI)

Table III: Other well defined immunodeficiency syndrome

A number of syndromes escape formal classification but are otherwise recognisable by particular clinical or immunological features.

1. Wiskott-Aldrich syndrome
   Wiskott-Aldrich syndrome
   Wiskott–Aldrich syndrome is a rare X-linked recessive disease characterized by eczema, thrombocytopenia , immune deficiency, and bloody diarrhea . It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954...
   
   
2. DNA repair
   DNA repair
   DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light and radiation can cause DNA damage, resulting in as many as 1...
   
    defects not causing isolated SCID: ataxia telangiectasia
   Ataxia telangiectasia
   Ataxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease...
   
   , ataxia-like syndrome
   MRE11A
   Double-strand break repair protein MRE11A is a protein that in humans is encoded by the MRE11A gene.-Interactions:MRE11A has been shown to interact with Ku70, Ataxia telangiectasia mutated, MDC1, Rad50, Nibrin, TERF2 and BRCA1.-Further reading:...
   
   , Nijmegen breakage syndrome
   Nijmegen breakage syndrome
   Nijmegen breakage syndrome , also known as Berlin breakage syndrome and Seemanova syndrome, is a rare autosomal recessive congenital disorder causing chromosomal instability, probably as a result of a defect in the Double Holliday junction DNA repair mechanism.NBS1 codes for a protein that has two...
   
   , Bloom syndrome
   Bloom syndrome
   Bloom's syndrome , also known as Bloom–Torre–Machacek syndrome, is a rare autosomal recessive chromosomal disorder characterized by a high frequency of breaks and rearrangements in an affected person's chromosomes. The condition was discovered and first described by dermatologist Dr...
   
   
3. DiGeorge syndrome
   DiGeorge syndrome
   22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome , DiGeorge anomaly, velo-cardio-facial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, Strong syndrome, congenital thymic aplasia, and thymic hypoplasia is a syndrome caused by the deletion of a...
   
    (when associated with thymic
   Thymus
   The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....
   
    defects)
4. Various immuno-osseous dysplasias (abnormal development of the skeleton with immune problems): cartilage-hair hypoplasia
   Cartilage-hair hypoplasia
   Cartilage–hair hypoplasia , also known as McKusick type metaphyseal chondrodysplasia, is a rare form of short-limbed dwarfism due to skeletal dysplasia. It was first reported in 1965 by McKusick et al...
   
   , Schimke syndrome
5. Hermansky-Pudlak syndrome
   Hermansky-Pudlak syndrome
   Hermansky–Pudlak syndrome is a rare autosomal recessive disorder which results in oculocutaneous albinism , bleeding problems due to a platelet abnormality , and storage of an abnormal fat-protein compound .There are eight classic forms of the disorder, based on the genetic mutation...
   
    type 2
6. Hyper-IgE syndrome
   Hyper-IgE syndrome
   Hyperimmunoglobulin E syndrome , also called Job's syndrome and Buckley syndrome, is a heterogeneous group of immune disorders.-Presentation:...
   
   
7. Chronic mucocutaneous candidiasis
   Chronic mucocutaneous candidiasis
   Chronic mucocutaneous candidiasis is an immune disorder of T cells. It is characterized by chronic infections with Candida that are limited to mucosal surfaces, skin, and nails. However, it can also be associated with other types of infections, such as human papilloma virus.An association with...
   
   
8. Hepatic venoocclusive disease with immunodeficiency
   Hepatic veno-occlusive disease
   Hepatic veno-occlusive disease or veno-occlusive disease is a condition in which some of the small veins in the liver are blocked. It is a complication of high-dose chemotherapy given before a bone marrow transplant and is marked by weight gain due to fluid retention, increased liver size, and...
   
    (VODI)
9. XL-dyskeratosis congenita (Hoyeraal-Hreidarsson syndrome)

Table IV: Diseases of immune dysregulaton

In certain conditions, the regulation rather than the intrinsic activity of parts of the immune system is the predominant problem.

1. Immunodeficiency with hypopigmentation or albinism
   Albinism
   Albinism is a congenital disorder characterized by the complete or partial absence of pigment in the skin, hair and eyes due to absence or defect of an enzyme involved in the production of melanin...
   
   : Chediak-Higashi syndrome
   Chédiak-Higashi syndrome
   Chédiak–Higashi syndrome is a rare autosomal recessive disorder that arises from a microtubule polymerization defect which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic infections, partial albinism and peripheral neuropathy...
   
   , Griscelli syndrome
   Griscelli syndrome
   Griscelli syndrome is a rare autosomal recessive disorder characterized by albinism with immunodeficiency, that usually causes death by early childhood.-Types:...
   
    type 2
2. Familial hemophagocytic lymphohistiocytosis
   Hemophagocytic lymphohistiocytosis
   Hemophagocytic lymphohistiocytosis , also known as hemophagocytic syndrome, is an uncommon hematologic disorder that, typically, clinically manifests as fever, hepatosplenomegaly, lymphadenopathy, jaundice and rash, with laboratory findings of lymphocytosis and histiocytosis, and the pathologic...
   
   : perforin
   Perforin
   Perforin-1 is a protein that in humans is encoded by the PRF1 gene.- Function :Perforin is a cytolytic protein found in the granules of CD8 T-cells and NK cells. Upon degranulation, perforin inserts itself into the target cell's plasma membrane, forming a pore. The lytic membrane-inserting part...
   
    deficiency, MUNC13D deficiency, syntaxin 11
   Syntaxin
   Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis.- Domains :Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain , and an N-terminal regulatory domain ....
   
    deficiency
3. X-linked lymphoproliferative syndrome
4. Syndromes with autoimmunity:
   1. (a) Autoimmune lymphoproliferative syndrome
      Autoimmune lymphoproliferative syndrome
      Autoimmune lymphoproliferative syndrome is a form of lymphoproliferative disorder. It affects lymphocyte apoptosis. It is a RASopathy.-Introduction:...
      
      : type 1a (CD95
      Fas receptor
      The FAS receptor also known as apoptosis antigen 1 , cluster of differentiation 95 or tumor necrosis factor receptor superfamily member 6 is a protein that in humans is encoded by the TNFRSF6 gene....
      
       defects), type 1b (Fas ligand
      FAS ligand
      Fas ligand is a type-II transmembrane protein that belongs to the tumor necrosis factor family. Its binding with its receptor induces apoptosis. Fas ligand/receptor interactions play an important role in the regulation of the immune system and the progression of cancer.- Structure :Fas ligand or...
      
       defects), type 2a (CASP10 defects), type 2b (CASP8 defects)
   2. (b) APECED
      Autoimmune polyendocrine syndrome
      In medicine, autoimmune polyendocrine syndromes are a heterogeneous group of rare diseases characterised by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected....
      
       (autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy)
   3. (c) IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked syndrome)
   4. (d) CD25 deficiency

Table V: Congenital defects of phagocyte number, function, or both

Phagocyte

Phagocyte

Phagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...

s are the cells that engulf and ingest pathogens (phagocytosis), and destroy them with chemicals. Monocyte

Monocyte

Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...

s/macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s as well as granulocyte

Granulocyte

Granulocytes are a category of white blood cells characterized by the presence of granules in their cytoplasm. They are also called polymorphonuclear leukocytes because of the varying shapes of the nucleus, which is usually lobed into three segments...

s are capable of this process. In certain conditions, either the number of phagocytes is reduced or their functional capacity is impaired.

1. Severe congenital neutropenia: due to ELA2 deficiency (with myelodysplasia)
2. Severe congenital neutropenia: due to GFI1
   GFI1
   Zinc finger protein Gfi-1 is a protein that in humans is encoded by the GFI1 gene.-Interactions:GFI1 has been shown to interact with PIAS3 and RUNX1T1.- External links :...
   
    deficiency (with T/B lymphopenia)
3. Kostmann syndrome
   Kostmann syndrome
   Kostmann syndrome, also known as severe congenital neutropenia, autosomal recessive type 3 and Kostmann disease, is a rare autosomal recessive form of severe chronic neutropenia usually detected soon after birth...
   
   
4. Neutropenia with cardiac and urogenital malformations
5. Glycogen storage disease type 1b
6. Cyclic neutropenia
   Cyclic neutropenia
   Cyclic neutropenia is a form of neutropenia that tends to occur every three weeks and lasting three to six days at a time due to changing rates of cell production by the bone marrow....
   
   
7. X-linked neutropenia/myelodysplasia
8. P14 deficiency
9. Leukocyte adhesion deficiency
   Leukocyte adhesion deficiency
   Leukocyte adhesion deficiency , is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. Leukocyte adhesion deficiency is divided into at least two subtypes: LAD1 and LAD2.-Characteristics:...
   
    type 1
10. Leukocyte adhesion deficiency
    Leukocyte adhesion deficiency
    Leukocyte adhesion deficiency , is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. Leukocyte adhesion deficiency is divided into at least two subtypes: LAD1 and LAD2.-Characteristics:...
    
     type 2
11. Leukocyte adhesion deficiency
    Leukocyte adhesion deficiency
    Leukocyte adhesion deficiency , is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. Leukocyte adhesion deficiency is divided into at least two subtypes: LAD1 and LAD2.-Characteristics:...
    
     type 3
12. RAC2
    Rac2
    Rac2 is a small signaling G protein , and is a member of the Rac subfamily of the family Rho family of GTPases...
    
     deficiency (Neutrophil immunodeficiency syndrome
    Neutrophil immunodeficiency syndrome
    Neutrophil immunodeficiency syndrome is a condition caused by mutations in the Rac2 gene.- See also :* Immunodeficiency with hyper-IgM* List of cutaneous conditions* Chronic granulomatous disease- References :...
    
    )
13. Beta-actin
    Beta-actin
    Beta-actin is one of six different actin isoforms which have been identified in humans. This is one of the two nonmuscle cytoskeletal actins. Actins are highly conserved proteins that are involved in cell motility, structure and integrity...
    
     deficiency
14. Localized juvenile periodontitis
15. Papillon-Lefèvre syndrome
16. Specific granule deficiency
17. Shwachman-Diamond syndrome
18. Chronic granulomatous disease
    Chronic granulomatous disease
    Chronic granulomatous disease is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens...
    
    : X-linked
19. Chronic granulomatous disease
    Chronic granulomatous disease
    Chronic granulomatous disease is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens...
    
    : autosomal (CYBA
    Cytochrome b-245, alpha polypeptide
    Cytochrome b-245 light chain is a protein that in humans is encoded by the CYBA gene involved in superoxide production and phagocytosis.-Further reading:...
    
    )
20. Chronic granulomatous disease
    Chronic granulomatous disease
    Chronic granulomatous disease is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens...
    
    : autosomal (NCF1
    NCF1
    Neutrophil cytosol factor 1 is a protein that in humans is encoded by the NCF1 gene.p47 is vital to the activation of NADPH oxidase. P47 becomes heavily phosphorylated-Interactions:...
    
    )
21. Chronic granulomatous disease
    Chronic granulomatous disease
    Chronic granulomatous disease is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens...
    
    : autosomal (NCF2
    NCF2
    Neutrophil cytosol factor 2 is a protein that in humans is encoded by the NCF2 gene.-Further reading:...
    
    )
22. IL-12
    Interleukin 12
    Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
    
     and IL-23 β1 chain deficiency
23. IL-12p40
    Interleukin 12
    Interleukin 12 is an interleukin that is naturally produced by dendritic cells, macrophages and human B-lymphoblastoid cells in response to antigenic stimulation.-Gene and structure:...
    
     deficiency
24. Interferon γ receptor 1
    Interferon-gamma
    Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
    
     deficiency
25. Interferon γ receptor 2
    Interferon-gamma
    Interferon-gamma is a dimerized soluble cytokine that is the only member of the type II class of interferons. This interferon was originally called macrophage-activating factor, a term now used to describe a larger family of proteins to which IFN-γ belongs...
    
     deficiency
26. STAT1
    STAT1
    STAT1 is a member of the Signal Transducers and Activators of Transcription family of transcription factors. STAT1 is involved in upregulating genes due to a signal by either type I, type II or type III interferons...
    
     deficiency (2 forms)
27. AD hyper-IgE
28. AR hyper-IgE
29. Pulmonary alveolar proteinosis
    Pulmonary alveolar proteinosis
    Pulmonary alveolar proteinosis is a rare lung disease in which abnormal accumulation of surfactant occurs within the alveoli, interfering with gas exchange. PAP can occur in a primary form or secondarily in the settings of malignancy , pulmonary infection, or environmental exposure to dusts or...
    
    

Table VI: Defects in innate immunity

Several rare conditions are due to defects in the innate immune system

Innate immune system

The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...

, which is a basic line of defence that is independent of the more advanced lymphocyte-related systems. Many of these conditions are associated with skin problems.

1. Hypohidrotic ectodermal dysplasia
   Hypohidrotic ectodermal dysplasia
   Hypohidrotic ectodermal dysplasia is one of about 150 types of ectodermal dysplasia in humans...
   
   
   1. NEMO
      IKBKG
      NF-kappa-B essential modulator also known as inhibitor of nuclear factor kappa-B kinase subunit gamma is a protein that in humans is encoded by the IKBKG gene. NEMO is a subunit of the IκB kinase that activates NF-κB. The human gene for IKBKG is located on chromosome Xq28...
      
       deficiency
   2. IKBA deficiency
2. EDA-ID
3. IRAK-4
   IRAK-4
   IRAK-4 , in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors....
   
    deficiency
4. MyD88
   Myd88
   Myeloid differentiation primary response gene is a protein that, in humans, is encoded by the MYD88 gene.-Function:In mice, MyD88 is a universal adapter protein as it is used by all TLRs to activate the transcription factor NF-κB. Mal is necessary to recruit Myd88 to TLR 2 and TLR 4, and MyD88...
   
    deficiency
5. WHIM syndrome
   WHIM syndrome
   WHIM Syndrome is a rare congenital immunodeficiency disorder characterized by chronic noncyclic neutropenia.-Diagnosis:...
   
    (warts, hypogammaglobulinaemia, infections, myleokathexis)
6. Epidermodysplasia verruciformis
   Epidermodysplasia verruciformis
   Epidermodysplasia verruciformis is an extremely rare autosomal recessive genetic hereditary skin disorder associated with a high risk of carcinoma of the skin. It is characterized by abnormal susceptibility to human papillomaviruses of the skin...
   
   
7. Herpes simplex encephalitis
8. Chronic mucocutaneous candidiasis
   Chronic mucocutaneous candidiasis
   Chronic mucocutaneous candidiasis is an immune disorder of T cells. It is characterized by chronic infections with Candida that are limited to mucosal surfaces, skin, and nails. However, it can also be associated with other types of infections, such as human papilloma virus.An association with...
   
   
9. Trypanosomiasis
   Trypanosomiasis
   Trypanosomiasis or trypanosomosis is the name of several diseases in vertebrates caused by parasitic protozoan trypanosomes of the genus Trypanosoma. Approximately 500,000 men, women and children in 36 countries of sub-Saharan Africa suffer from human African trypanosomiasis which is caused by...
   
   

Table VII: Autoinflammatory disorder

Rather than predisposing for infections, most of the autoinflammatory disorders lead to excessive inflammation. Many manifest themselves as periodic fever syndrome

Periodic fever syndrome

The periodic fever syndromes are a set of disorders, many of which are genetic disorders in which the mechanisms which initiate and control inflammation are disturbed, leading to uncontrolled inflammation throughout the body...

s. They may involve various organs directly, as well as predisposing for long-term damage (e.g. by leading to amyloid

Amyloid

Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...

 deposition).

1. Familial Mediterranean fever
   Familial Mediterranean fever
   Familial Mediterranean fever is a hereditary inflammatory disorder. FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin....
   
   
2. TNF receptor associated periodic syndrome
   TNF receptor associated periodic syndrome
   TNF receptor associated periodic syndrome is a periodic fever syndrome associated with mutations in a receptor for the molecule tumor necrosis factor that is inheritable in an autosomal dominant manner...
   
    (TRAPS)
3. Hyper-IgD syndrome (HIDS)
4. CIAS1
   CIAS1
   NACHT, LRR and PYD domains-containing protein 3 or cryopyrin is a protein that in humans is encoded by the NLRP3 gene. The gene is also called cold induced autoinflammatory syndrome 1 and is located on the long arm of chromosome 1...
   
   -related diseases:
   1. Muckle-Wells syndrome
      Muckle-Wells syndrome
      Muckle–Wells syndrome , also known as , is a rare autosomal dominant disease which causes sensorineural deafness, recurrent hives, and can lead to amyloidosis. Individuals with MWS often have episodic fever, chills, and painful joints. As a result, MWS is considered a type of periodic fever syndrome...
      
      
   2. Familial cold autoinflammatory syndrome
   3. Neonatal onset multisystem inflammatory disease
      Neonatal onset multisystem inflammatory disease
      Neonatal onset multisystem inflammatory disease is a rare genetic periodic fever syndrome which causes uncontrolled inflammation in multiple parts of the body starting in the newborn period...
      
      
5. PAPA syndrome
   PAPA syndrome
   PAPA syndrome is an acronym for pyogenic arthritis, pyoderma gangrenosum and acne. It is a rare genetic disorder characterised by its effects on skin and joints.- Genetics :...
   
    (pyogenic sterile arthritis, pyoderma gangrenosum, acne)
6. Blau syndrome
   Blau syndrome
   Blau syndrome is characterized by familial granulomatous arthritis, iritis, and skin granulomas, comprising an autosomal dominantly inherited syndrome that overlaps both sarcoidosis and granuloma annulare....
   
   
7. Chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia (Majeed syndrome
   Majeed syndrome
   Majeed syndrome is an inherited skin disorder characterized by chronic multifocal osteomyelitis, congenital dyserythropoietic anemia and a neutrophilic dermatosis....
   
   )
8. DIRA
   Dira
   Dira is a town in the Solenzo Department of Banwa Province in western Burkina Faso. As of 2005 it had a population of 3,209.-References:...
   
    (deficiency of the IL-1 receptor antagonist)

Table VIII. Complement deficiencies

The complement system

Complement system

The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...

 is part of the innate as well as the adaptive immune system; it is a group of circulating proteins that can bind pathogens and form a membrane attack complex. Complement deficiencies

Complement deficiency

Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins.The disorders can be divided into two categories:...

 are the result of a lack of any of these proteins. They may predispose to infections but also to autoimmune conditions.

1. C1q deficiency
   C1Q complex
   The C1q complex is potentially multivalent for attachment to the complement fixation sites of immunoglobulin.The sites are on the CH2 domain of IgG and, it is thought, on the CH4 domain of IgM....
   
    (lupus-like syndrome, rheumatoid disease, infections)
2. C1r deficiency
   Complement component 1R
   Complement component 1R is a protein involved in the complement system....
   
    (idem)
3. C1s deficiency
4. C4 deficiency
   Complement component 4
   Complement component 4 is a protein involved in the complement system.It is cleaved into proteins 4a and 4b.* C4a is an anaphylatoxin.* C4b forms part of C3-convertase, in conjunction with 2a:* C4b can bind CR1....
   
    (idem)
5. C2 deficiency
   Complement component 2
   Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical pathway of complement system.-Further reading:...
   
    (lupus-like syndrome, vasculitis, polymyositis, pyogenic infections)
6. C3 deficiency
   C3 (complement)
   Complement component 3, often simply called C3, is a protein of the immune system. It plays a central role in the complement system and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3.-Function:...
   
    (recurrent pyogenic infections)
7. C5 deficiency
   Complement component 5
   Complement component 5 is a protein that in humans is encoded by the C5 gene.Complement component 5 is involved in the complement system. It is cleaved into C5a and C5b:* C5a plays an important role in chemotaxis....
   
    (Neisserial infections, SLE)
8. C6 deficiency
   Complement component 6
   Complement component 6 is a protein that in humans is encoded by the C6 gene.Complement component 6 is a protein involved in the complement system. It is part of the membrane attack complex which can insert into the cell membrane and cause cell to lyse....
   
    (idem)
9. C7 deficiency
   Complement component 7
   Complement component 7 is a protein involved in the complement system....
   
    (idem, vasculitis)
10. C8a deficiency
    C8 complex
    Complement component 8 is a protein involved in the complement system. A hereditary deficiency of C8 can result in increased susceptibility to Neisseria infections, such as meningitis and gonorrhea.-References:...
    
    
11. C8b deficiency
    C8 complex
    Complement component 8 is a protein involved in the complement system. A hereditary deficiency of C8 can result in increased susceptibility to Neisseria infections, such as meningitis and gonorrhea.-References:...
    
    
12. C9 deficiency
    Complement component 9
    Complement component 9 is a protein involved in the complement system....
    
     (Neisserial infections)
13. C1-inhibitor deficiency
    Angioedema
    Angioedema or Quincke's edema is the rapid swelling of the dermis, subcutaneous tissue, mucosa and submucosal tissues. It is very similar to urticaria, but urticaria, commonly known as hives, occurs in the upper dermis...
    
     (hereditary angioedema)
14. Factor I deficiency
    Complement factor I
    Complement factor I, also known as C3B/C4B inactivator, is a protein that in humans is encoded by the CFI gene.Complement Factor I is a protein of the complement system, first isolated in 1966 in guinea pig serum that regulates complement activation by cleaving cell-bound or fluid phase C3b and...
    
     (pyogenic infections)
15. Factor H deficiency
    Factor H
    Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large , soluble glycoprotein that circulates in human plasma...
    
     (haemolytic-uraemic syndrome, membranoproliferative glomerulonephritis
    Membranoproliferative glomerulonephritis
    Membranoproliferative glomerulonephritis , also known as mesangiocapillary glomerulonephritis, is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane thickening, activating complement and damaging the glomeruli.MPGN accounts for approximately 4%...
    
    )
16. Factor D deficiency (Neisserial infections)
17. Properdin deficiency
    Properdin
    Properdin or factor P is a globulin protein found in the blood serum of more complex animals. In the complement system, an innate-immunity series of proenzymes dissolved in the circulation, it is also called "Factor P".-Function:...
    
     (Neisserial infections)
18. MBP deficiency
    Mannan-binding lectin
    Mannose-binding lectin , also named mannose- or mannan-binding protein , is an important factor in innate immunity.-Function:MBL belongs to the class of collectins in the C-type lectin superfamily, whose function appears to be pattern recognition in the first line of defense in the pre-immune...
    
     (pyogenic infections)
19. MASP2 deficiency
    MASP2 (protein)
    Mannan-binding lectin serine protease 2 also known as mannose-binding protein-associated serine protease 2 is an enzyme that in humans is encoded by the MASP2 gene....
    
    
20. Complement receptor 3 (CR3) deficiency
21. Membrane cofactor protein (CD46) deficiency
22. Membrane attack complex inhibitor (CD59) deficiency
23. Paroxysmal nocturnal hemoglobinuria
    Paroxysmal nocturnal hemoglobinuria
    Paroxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis...
    
    
24. Immunodeficiency associated with ficolin 3 deficiency

Treatment

The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. This may range from immunoglobulin replacement therapy in antibody deficiencies—in the form of intravenous immunoglobulin

Intravenous immunoglobulin

Intravenous immunoglobulin is a blood product administered intravenously. It contains the pooled IgG extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months...

 (IVIG) or subcutaneous immunoglobulin (SCIG)—to hematopoietic stem cell transplantation for SCID and other severe immunodeficiences. Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotic

Antibiotic

An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s may be advised.

Epidemiology

A survey of 10,000 American households revealed that the prevalence of diagnosed primary immunodeficiency approaches 1 in 1200. This figure does not take into account people with mild immune system defects who have not received a formal diagnosis.

Milder forms of primary immunodeficiency, such as selective immunoglobulin A deficiency

Selective immunoglobulin A deficiency

Selective immunoglobulin A deficiency is a relatively mild genetic immunodeficiency. People with this deficiency lack immunoglobulin A , a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract. It is defined as an undetectable...

, are fairly common, with random groups of people (such as otherwise healthy blood donors) having a rate of 1:600. Other disorders are distinctly more uncommon, with incidences between 1:100,000 and 1:2,000,000 being reported.

External links

• Immune Deficiency Foundation
• European Society for Immunodeficiencies (ESID)
• International Union of Immunological societies (IUIS)
• Primary Immunodeficiency Resource Center (Jeffrey Modell Foundation)
• International Patient Organisation for Primary Immunodeficiencies (IPOPI)