Heavy chain disease
Encyclopedia
Heavy chain disease is a form of paraproteinemia
with a proliferation of cells producing immunoglobulin heavy chains.
This disease is characterized by an excessive production of heavy chains that are short and truncated. These heavy chain disease proteins have various deletions, mainly in their amino-terminal part, which causes the heavy chains to lose the ability to form disulfide bond
s with the light chain
s. The defect in the immunoglobulins presumably arises during somatic hypermutation. Deletion of the N-terminal part of the heavy chain disease protein leads to aggregation and signaling of the B cell receptor, presumably due to the loss of the anti-aggregating properties of the light chain.
It is characterized by lymphadenopathy,fever,anemia ,malaise,hepatosplenomegaly and weakness. Most distinctive symptom is palatal edema,caused by nodal involvement of Waldeyer's ring.
Diagnosis is made by the demonstration of an anomalous serum M component, that reacts with anti-IgG but not anti-light chain reagents. Bone marrow examination is usually nondiagnostic.
Patients usually have a rapid downhill course and die of infection.
IgM and IgG heavy chain diseases, which are known as μHCD and γHCD respectively, are fairly common and are present in various tissues.
The γHCD can be divided into three categories based on the various clinical and pathological features. These categories are disseminated lymphoproliferative disease, localized proliferative disease and no apparent proliferative disease.
Paraproteinemia
Paraproteinemia, or monoclonal gammopathy, is the presence of excessive amounts of a single monoclonal gammaglobulin in the blood...
with a proliferation of cells producing immunoglobulin heavy chains.
This disease is characterized by an excessive production of heavy chains that are short and truncated. These heavy chain disease proteins have various deletions, mainly in their amino-terminal part, which causes the heavy chains to lose the ability to form disulfide bond
Disulfide bond
In chemistry, a disulfide bond is a covalent bond, usually derived by the coupling of two thiol groups. The linkage is also called an SS-bond or disulfide bridge. The overall connectivity is therefore R-S-S-R. The terminology is widely used in biochemistry...
s with the light chain
Light chain
A light chain is the small polypeptide subunit of a protein complex.More specifically, it can refer to:* Immunoglobulin light chain* Ferritin light chain* Myosin light chain* Kinesin light chain* Dynein light chainLight chain may also refer to:...
s. The defect in the immunoglobulins presumably arises during somatic hypermutation. Deletion of the N-terminal part of the heavy chain disease protein leads to aggregation and signaling of the B cell receptor, presumably due to the loss of the anti-aggregating properties of the light chain.
Classification
There are four forms:- alpha chain disease (Seligmann's disease)
- gamma chain disease (Franklin's disease)
- mu chain disease
- delta chain disease
IgA/αHCD
The most common type of heavy chain disease is the IgA type, known as αHCD. The most common type of αHCD is the digestive form, however it has also been reported in the respiratory tract, and other areas of the body.IgG/γHCD
Franklin's disease (gamma heavy chain disease)It is characterized by lymphadenopathy,fever,anemia ,malaise,hepatosplenomegaly and weakness. Most distinctive symptom is palatal edema,caused by nodal involvement of Waldeyer's ring.
Diagnosis is made by the demonstration of an anomalous serum M component, that reacts with anti-IgG but not anti-light chain reagents. Bone marrow examination is usually nondiagnostic.
Patients usually have a rapid downhill course and die of infection.
IgM and IgG heavy chain diseases, which are known as μHCD and γHCD respectively, are fairly common and are present in various tissues.
The γHCD can be divided into three categories based on the various clinical and pathological features. These categories are disseminated lymphoproliferative disease, localized proliferative disease and no apparent proliferative disease.
- Disseminated lymphoproliferative disease is found in 57-66% of patients diagnosed with γHCD. Lymphadenopathy and constitutional symptoms are the usual features.
- Localized proliferative disease is found in approximately 25% of γHCD patients. This is characterized by a localization of the mutated heavy chains in extramedullary tissue, or solely in the bone marrow.
- No apparent proliferative disease is seen in 9-17% of patients with γHCD, and there is almost always an underlying autoimmune disorder in these patients.