Genetic studies in multiple myeloma. II. Immunoglobulin allotype associations

Abstract

A weakly positive but statistically significant association between HLA‐Cw5 and myeloma has been reported in black patients. The authors attempted to determine whether immunoglobulin allotypes of the Gm series demonstrate any such association. They were identified in the sera of 29 black patients and 160 healthy black control subjects by a standard hemagglutination‐inhibition technique. The results indicate that the G3m(g5) allotype is significantly associated with myeloma. Furthermore, addition of that immunoglobulin allotype to a Gm phenotype that is netatively associated with myeloma gives a phenotype that is positively associated with the disease, both associations being statistically significant. It was concluded that G3m(g5) is a marker of inherited susceptibility to myeloma in black Americans. Furthermore, as G3m(g5) is present in almost 50% of normal control subjects, it was proposed that its expression in a much greater proportion of patients may be related to an underlying genetic rearrangement that is also associated with neoplastic transformation.

Role of immune stimulation in the etiology of multiple myeloma: A case control study

“…This is quite analogous to the situation for the inducible mouse myeloma tumor wherein tumors can be induced with chronic immune stimuli and irritants only in certain genetically predisposed species of mice [7,8]. It is also compatible with the evidence that there is at least some genetic component to the etiology of myeloma in man [7,13,15,26]. The possibility of an actual protective effect from manifestations of such prior exposure in patients destined to have myeloma is suggested, but only weakly.…”

Disparities in black and white patients with multiple myeloma referred for autologous hematopoietic transplantation: A single center study

“…A recent study suggested a link between MGUS/MM and chronic immune stimulation due to autoimmune diseases, acquired infections, and inflammatory conditions . Other studies have linked specific human leukocyte antigens (HLAs) (HLA‐Bw65, HLA‐Cw5, and HLA‐DRw14) to MM . Recently, hyperphosphorylated paratarg‐7, a defined autosomal dominantly inherited risk factor for MGUS and MM, was found in 11 of 100 African American (11.0%), 8 of 550 European (1.5%), and 1 of 278 Japanese (0.4%) healthy controls ( P <.001), suggesting a genetic predisposition in black individuals .…”

A biased Gm haplotype and Gm paraprotein allotype in multiple myeloma suggests a role for the Gm system in myeloma development

“…The increased frequency of a Gm allotype in a group of patients susceptible to a particular disease may be related to the allotype itself or to the haplotype containing it (Whittingham & Propert, 1986). Myeloma has been found to be associated with a low frequency of G1m(f) in an Irish population (Blake & Greally, 1975) and with a high frequency of G3m(g5) in black Americans (Leech et al ., 1985). However, the relationship between the Gm haplotype, which represents the inherited combination of Gm allotypes, and the Gm allotype expressed on the IgG paraprotein, which reflects the enhanced gene expression within the haplotype in multiple myeloma, has remained undetermined.…”