Occurrence of heavy chain of 7S IgM half-molecule whose NH2-terminal sequence is identical with that of kappa light chain sequence in patients with Waldenstrom macroglobulinemia

We report a rare case of a half molecule 7S IgM (HM 7SIgM) consisting of a unique mu heavy chain and kappa light chain found in blood and urine sample s from a patient with primary Waldenstrom macroglobulinemia. A 64kDa abnorm al immunoglobulin was detected in serum and urine by immunoblot method, and purified by a two-dimensional SDS-PAGE after separation from IgG and album in fractions on gel filtration. NH2-terminal amino acid sequence analysis o f the heavy chain revealed that residues 1-20 were identical to those of th e NH2-terminal region of kappa light chain derived from the same patient. T his sequence was then followed by a sequence that could not be identified b y a computer homology search on the protein database. Using polypeptide seg ments obtained from the unique mu chain by digestion with endopeptidase, we identified a sequence spanning from residue 127 in the variable region of the known mu chain to residue 19 in the known CH1 domain and a sequence spa nning from residues 67-82 in the heavy chain variable region class II. From these results, we concluded that the 64 kDa protein was an abnormal half m olecule 7S IgM consisting of a kappa light chain and a unique mu heavy chai n of 35 kDa polypeptide in which the NH2-terminal 20 amino acids were repla ced by 20 amino acids derived from the sequence of kappa light chain in the NH2-terminal region. (C) 1999 Elsevier Science B.V. All rights reserved.