Large quantities of low molecular weight IgM in mixed cryoglobulinaemia

Low molecular weight (LMW) IgM is the monomeric subunit of pentameric IgM. It was not found in the sera of 20 healthy subjects but was detected in all six patients with mixed cryoglobulinaemia with a mean value of 1.4 g/l, representing 34% of the total IgM. In three of four patients studied LMW IgM was monoclonal and of the same light chain type (kappa) as the pentameric monoclonal IgM rheumatoid factor (RF) observed in the cryoprecipitate. LMW IgM was proportionately under-represented, however, in the cryoprecipitate compared with the corresponding serum, possibly because of the lower valency of the LMW molecule. Immunoblot analysis of sera showed the presence of other oligomers of IgM in addition to monomeric IgM, suggesting that a disorder of IgM assembly was responsible for its occurrence, and this was supported by the secretion of large proportions of LMW IgM in vitro by peripheral blood mononuclear cells (PBMC) from one patient with this disorder but not from healthy controls. In conclusion, the occurrence of large quantities of monoclonal LMW IgM in mixed cryoglobulinaemia was observed, and it is suggested that this is unlikely to have a direct pathogenic significance. It is postulated that its presence reflects a disturbance of assembly of the monomeric IgM subunits that occurs during the polymerization of the pentameric molecule.