Multiple anomalous immunoglobulins. Clinical, structural and cellular studies in three patients

Coexistence of several abnormal immunoglobulins raises the question of whether a single tumor or several different tumors account for the serum changes. This situation also presents a unique opportunity to investigate the biologic question of whether or not single clones of lymphocytes or plasma cells can produce more than one category of immunoglobulins. Multiple anomalous immunoglobulin classes are described in three patients with lymphoproliferative disorders. One patient (E.E.) had three anomalous proteins (G-myeloma protein, A-myeloma protein and Waldenström macroglobulin) in the serum plus Bence Jones protein in the urine. Two patients had both G-myeloma protein and Waldenström macroglobulin in the serum. Clinical manifestations in two patients were distinctly different from those observed in multiple myeloma and more nearly resembled macroglobulinemic lymphoma. The third patient had an oral plasmacytoma. Histologic examination of tisues in the three patients indicated a proliferative disorder of lymphocyticplasmocytic type not distinguishable from the macroglobulinemia of Waldenström. Biosynthetic studies, in vitro, of the bone marrow and available tumor tissue revealed synthesis of all the anomalous immunoglobulins seen in the serum. Immunofluorescent studies in the patient with three anomalous immunoglobulins (E.E.) indicated that single cells were capable of producing at least two of the abnormal proteins. These findings indicate that the separate proteins were formed in a single neoplastic clone, rather than by separate tumors. In each of the patients the light chains in the abnormal proteins were antigenically similar i.e., either all kappa (κ) or all lambda (λ). Acrylamide gel electrophoresis and peptide comparisons and Inv (kappa chain) and O₂ (lambda chain) antigen comparisons, however, revealed that the paraprotein light chains differed in each patient. These findings indicate that each anomalous immunoglobulin had distinctive light and heavy polypeptide chains. Apparently each tumor was synthesizing two or more forms of heavy and light immunoglobulin polypeptide chains.