Heavy Chain Disease
Heavy chain disease, also known as Franklin disease, is a rare variant of B cell lymphoproliferative disorder which produces monoclonal heavy chains without associated light chains. Three types of heavy chain disease have been reported: alpha, gamma and mu. Heavy chain disease is caused by mutations in the constant-1 domain of IgG chain gene, which affects the region of the heavy chain responsible for binding light chains. This mutation not only results in the failure to bind light chains but also the inability to bind heat shock protein 78. This latter defect prevents heat shock mediated degradation of heavy chains leading to their accumulation in plasma.
Approximately two thirds of patients present with disseminated lymphoproliferative disease with lymphadenopathy and constitutional symptoms. Approximately one fourth of patients present with lymphoma limited to the bone marrow or with localized extra nodal disease most commonly involving the skin. Approximately 10% of patients have no evidence of lymphoplasmacytic disease at the time of diagnosis. Most patients in this latter group have an underlying autoimmune disease.
The diagnosis of heavy chain disease is established with serum protein electrophoresis and immunofixation which confirm the presence of monoclonal heavy chain without associated light chains. Detection of monoclonal heavy chains can be difficult because heavy chains may appear as a broader band than is typically seen with monoclonal proteins. Second, heavy chains often migrate in alpha-2 to beta region, where they may be masked by other proteins. Sometimes a combination of capillary zone electrophoresis, immuno-subtraction and gel immunofixation is required to confirm the diagnosis.
Reference
Bosman MCJ et al. Broad bands observed in serum electrophoresis should not be taken lightly. Clin Chem 2019;65:618-21.
Bianchi G, etal. The heavy chain diseases: clinical and pathologic features. Oncology 2014;28:45-53.
