Common variable immunodeficiency - AbsoluteAstronomy.com

Common variable immunodeficiency (CVID) (also known as Acquired hypogammaglobulinemia) is a group of approximately 150 primary immunodeficiencies

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,...

(PIDs), which have a common set of symptoms (including hypogammaglobulinemia

Hypogammaglobulinemia

Hypogammaglobulinemia is a type of immune disorder characterized by a reduction in all types of gamma globulins.Hypogammaglobulinemia is a characteristic of common variable immunodeficiency.-Terminology:...

) but which have different underlying causes.

Common variable immunodeficiency is the most commonly encountered primary immunodeficiency

Primary immunodeficiency

Primary immunodeficiencies are disorders in which part of the body's immune system is missing or does not function properly. To be considered a primary immunodeficiency, the cause of the immune deficiency must not be secondary in nature...

Causes and types

CVID is believed to be a genetically determined primary immune defect; however, the underlying causes are different. The result of these defects is that the patient doesn't produce sufficient antibodies in response to exposure to pathogen

Pathogen

A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

s. As a result, the patient'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...

fails to protect them against common bacteria

Bacteria

Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

l and viral

Virus

A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

(and occasionally parasitic and protozoan) infections. The net result is that the patient is susceptible to illness.

In CVID, the B cells are affected. In severe combined immunodeficiency (SCID), a more severe condition than CVID, diagnosed in infancy, both parts of the immune system (the cellular

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...

and humoral system) are affected, hence its classified as combined immunodeficiency.

CVID appears to include a number of defects, some of which have been identified. For the majority, the genetic causes are still unknown.

ICOS

CD278

Inducible T-cell costimulator is a protein that in humans is encoded by the ICOS gene.CD278 or ICOS is a CD28-superfamily costimulatory molecule that is expressed on activated T cells...

, TACI and CD19

CD19

B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...

have been identified as candidates.

It is possible that environmental agents or a virus provoke the immune defect, due to genetic predisposition, but this has not been clarified.

Types include:

Type	OMIM	Gene
CVID1		ICOS CD278 Inducible T-cell costimulator is a protein that in humans is encoded by the ICOS gene.CD278 or ICOS is a CD28-superfamily costimulatory molecule that is expressed on activated T cells...
CVID2		TACI
CVID3		CD19 CD19 B-lymphocyte antigen CD19 also known as CD19 , is a protein that in humans is encoded by the CD19 gene.- Function :...
CVID4		TNFRSF13C TNFRSF13C Tumor necrosis factor receptor superfamily member 13C is a protein that in humans is encoded by the TNFRSF13C gene.-Further reading:...
CVID5		CD20 CD20 B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity....
CVID6		CD81 CD81 CD81 molecule, also known as CD81 , is a protein which in humans is encoded by the CD81 gene...

Clinical Features

Signs and Symptoms of CVID include:

Hypogammaglobulinemia: low levels of immunoglobulin G
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%...

(IgG), immunoglobulin A
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....

(IgA) and/or immunoglobulin M
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...

(IgM).
Poor titer response to vaccination with polysaccharide
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...

and protein antigens (e.g. pneumococci, tetanus, and diphtheria).
Recurring infections involving the ears, eyes, sinuses, nose, bronchi, lungs, skin, GI tract, joints, bones, CNS, parotid glands, etc. These infections respond to antibiotics but recur upon discontinuation of the medications. Bronchiectasis can occur from severe and recurrent lung infections.
Viral infections that usually respond to antivirals
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

.
Enlarged lymph nodes, Enlarged spleen
Splenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...

.
Fatigue.
Abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...

, Bloating
Bloating
Bloating is any abnormal general swelling, or increase in diameter of the abdominal area. As a symptom, the patient feels a full and tight abdomen, which may cause abdominal pain sometimes accompanied by increased borborygmus or more seriously the total lack of borborygmus.-Symptoms:The most common...

, Nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, Vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

, Diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

, Weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

.
Malabsorption
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...

.
Helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...

, Giardiasis
Giardiasis
Giardiasis or beaver fever in humans is a diarrheal infection of the small intestine by a single-celled organism Giardia lamblia. Giardiasis occurs worldwide with a prevalence of 20–30% in developing countries. In the U.S., 20,000 cases are reported to the CDC annually, but the true annual...

, Cryptosporidiosis
Cryptosporidiosis
Cryptosporidiosis, also known as crypto, is a parasitic disease caused by Cryptosporidium, a protozoan parasite in the phylum Apicomplexa. It affects the intestines of mammals and is typically an acute short-term infection...

, Small bowel bacterial overgrowth syndrome
Small bowel bacterial overgrowth syndrome
Small bowel bacterial overgrowth syndrome , or small intestinal bacterial overgrowth , also termed bacterial overgrowth; is a disorder of excessive bacterial growth in the small intestine. Unlike the colon , which is rich with bacteria, the small bowel usually has less than 104 organisms per...

, etc.
Atrophic gastritis
Atrophic gastritis
Atrophic gastritis is a process of chronic inflammation of the stomach mucosa, leading to loss of gastric glandular cells and their eventual replacement by intestinal and fibrous tissues...

with pernicious anemia
Pernicious anemia
Pernicious anemia is one of many types of the larger family of megaloblastic anemias...

and achlorhydria
Achlorhydria
Achlorhydria or hypochlorhydria refers to states where the production of gastric acid in the stomach is absent or low, respectively. It is associated with various other medical problems.-Signs and symptoms:...

.
Nodular lymphoid hyperplasia of the GI tract.
Villous atrophy of the small intestine, which can resemble celiac disease.
Inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...

.
Aphthous stomatitis.
Increased intestinal permeability.
Polyarthritis
Polyarthritis
Polyarthritis is any type of arthritis which involves 5 or more joints simultaneously. It is usually associated with autoimmune conditions.Polyarthritis may be experienced at any age and is not gender specific.-Causes:...

, or joint pain, spread across most joints, but specifically finger
Finger
A finger is a limb of the human body and a type of digit, an organ of manipulation and sensation found in the hands of humans and other primates....

s, wrist
Wrist
In human anatomy, the wrist is variously defined as 1) the carpus or carpal bones, the complex of eight bones forming the proximal skeletal segment of the hand;...

s, elbows, toe
Toe
Toes are the digits of the foot of a tetrapod. Animal species such as cats that walk on their toes are described as being digitigrade. Humans, and other animals that walk on the soles of their feet, are described as being plantigrade; unguligrade animals are those that walk on hooves at the tips of...

s, ankle
Ankle
The ankle joint is formed where the foot and the leg meet. The ankle, or talocrural joint, is a synovial hinge joint that connects the distal ends of the tibia and fibula in the lower limb with the proximal end of the talus bone in the foot...

s and knee
Knee
The knee joint joins the thigh with the leg and consists of two articulations: one between the fibula and tibia, and one between the femur and patella. It is the largest joint in the human body and is very complicated. The knee is a mobile trocho-ginglymus , which permits flexion and extension as...

s. In some cases, Mycoplasma can be the cause.
Children may show a "failure to thrive
Failure to thrive
Failure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....

" - they may be underweight and underdeveloped compared with "normal" peers.
Candida
Candida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...

infection of the lungs.
Anxiety and depression, usually as a result of dealing with the other symptoms.

Diagnosis

Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...

of CVID is usually made by demonstrating low levels of immunoglobulins in the serum. Diagnosis may be made rapidly, but is often delayed; it is usually made in the second or third decade of life after referral to an immunologist.

Diagnosis of CVID is a diagnosis of exclusion

Diagnosis of exclusion

A diagnosis of exclusion is a medical condition reached by a process of elimination, which may be necessary if presence cannot be established with complete confidence from examination or testing...

.

Diagnoses to exclude include loss of protein from the kidneys or reduced antibody production secondary to chronic lymphocytic leukemia

Chronic lymphocytic leukemia

B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...

or multiple myeloma

Multiple myeloma

Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...

.

It presents similar to 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...

, but the conditions can be distinguished with flow cytometry

Flow cytometry

Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...

Associated conditions

As with several other immune cell disorders, CVID may predispose to 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...

or possibly stomach cancer

Stomach cancer

Gastric cancer, commonly referred to as stomach cancer, can develop in any part of the stomach and may spread throughout the stomach and to other organs; particularly the esophagus, lungs, lymph nodes, and the liver...

. There also appears to be a predilection for 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...

s, with a risk of up to 25%. Autoimmune destruction of platelet

Platelet

Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...

s or red blood cell

Red blood cell

Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...

s are the most common of these.

Treatment

Treatment usually consists of immunoglobulin therapy, which is an injection of human antibodies harvested from plasma donations:

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, most common treatment in the US)
subcutaneous immunoglobulin G (SCIG, relatively new treatment in the US and UK)
intramuscular immunglobulin (IMIG, less effective, painful)

This is not a cure, but it strengthens immunity

Immunity (medical)

Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...

by ensuring that the patient has "normal" levels of antibodies, which helps to prevent recurrent upper respiratory infections.

IG therapy can't be used if the patient has anti-IgA antibodies but in this case, products low in IgA can be used; subcutaneous delivery also is a means of permitting such patients to have adequate antibody replacement.

IVIG treatment can be received by patients with a complete IgA deficiency if the IgA is completely removed from the treatment.

Reactions

Some CVID patients may experience reactions to IG therapies; reactions may include:

anaphylactic shock (very rare)
hives (rare)
chills
difficulty breathing
headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

(relatively common, may be relieved by an antihistamine, paracetamol/acetaminophen, or an anti-inflammatory (naproxen, advil, aspirin)
nausea (common in IVIG)
fever (common in IVIG and rare in SCIG)
aseptic meningitis (rare)
severe fatigue (common in IVIG)
muscle aches and pain, or joint pain
thrombotic events (rare)
swelling at the insertion site (common in SCIG)

Patients should not receive therapy if they are fighting an active infection as this increases the risk of reaction. Also, patients changing from one brand of product to another may be at higher risk of reaction for the first couple of treatments on the new brand.

Reactions can be minimized by taking an antihistamine

Antihistamine

An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...

and/or hydrocortisone and some paracetamol/acetaminophen/anti-inflammatory (naproxen, advil, aspirin) prior to treatment; patients should also be thoroughly hydrated and continue to drink water before, after and during treatment (if possible). IVIG should be prepared soon before IVIG infusion. Patient using a heating pad or warm blanket can help alleviate chills.

Research

Research is currently focussing on genetic analysis, and in differentiating between the various disorders in order to allow a cure to be developed. Cures are likely to be genetic in nature, repairing faulty genes and allowing the individual to start producing antibodies. Funding for research in the US is provided by the National Institutes of Health. Key research in the UK is funded by the Primary Immunodeficiency Association (PiA), and funding is raised through the annual Jeans for Genes campaign.

Epidemiology

CVID has an estimated prevalence of about 1:50,000. The typical patient is between 20 and 40, and males and females are equally affected. About 20% of patients are diagnosed in childhood.

History

Charles Janeway, Sr. is generally credited with the first description of a case of CVID in 1953.

External links

The source of this article is wikipedia, the free encyclopedia. The text of this article is licensed under the GFDL.