Hypergammaglobulinemia and oligo-/monoclonal gammopathy in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias and variable immunodeficiency. Chromosomal instability, increased sensitivity to ionizing radiation and a high incidence of hematolymphoid malignancies are other salient features of this disease. The occurrence of hypergammaglobulinemia and oligo-/monoclonal gammopathy in A-T has received little attention. This prompted us to investigate the presence of these abnormalities in 55 patients seen at the Johns Hopkins A-T clinic. 18 patients had hypergammaglobulinemia: 16 had high IgM and two high IgA levels. Immunofixation electrophoresis (IFE) was performed on 38 of the sera. This revealed four cases of gammopathy: 1) an IgM κ and IgM λ oligoclonal gammopathy, 2) an IgM κ monoclonal gammopathy. This patient developed the hyperviscosity syndrome. After chemotherapy, her IFE showed an IgG κ and an IgM λ bidonal gammopathy, 3) an IgM λ monoclonal gammopathy that progressed to an IgM κ and IgM λ oligoclonal gammopathy, and 4) an IgA κ monoclonal gammopathy. Our data show that oligo-/monoclonal gammopathies in A-T patients may involve any of the main immunoglobulin isotypes. They underscore the need to search for the presence of monoclonal gammopathy in A-T patients. Finally, the variable course of the process makes it necessary to develop prognostic and therapeutic guidelines for gammopathies that emerge in patients with A-T.