Multiple myeloma in two brothers. An immunochemical and immunogenetic familial study

When multiple myeloma was diagnosed within 6 months in two brothers a family study was carried out in 34 relatives to assess the genetic factors involved. The monoclonal immunoglobulin isotype identified was identical for the two brothers (IgG kappa) as well as their genotype (a = A2B12BfsDR4 GIo2/d: A9B27BfsDR2GIol). Blood protein electrophoresis and the major histocompatibility complex markers (HLA A, B, DR Bf, glyoxalase phenotypes) were also determined in the other family members. The immunochemical study revealed no other case of monoclonal gammapathy, but 12 cases of low gamma-globulin and three cases of polyclonal hypergammapathy were found. The immunogenetic study showed that no other family member had the a/d genotype of the two brothers, whereas nine family members were semi-identical for haplotype a and five for haplotype d. It is unlikely that a double immunochemical and immunogenetic identity in two siblings with multiple myeloma would be due only to random encounter, rather this finding suggests that, besides environmental factors, genetic factors may be involved in the pathogenesis. Systematic immunochemical and immunogenetic studies in familial multiple myeloma are proposed as a method to further elucidate an eventual genetic background in multiple myeloma.