IgM paraproteinaemia: disease associations and laboratory features

To review the disease associations and laboratory features occurring in IgM paraproteinaemia.

Systematic review of all new serum IgM paraproteins detected over a 6-year period in an immunodiagnostic laboratory serving a population of 400,000 people. Clinical diagnoses were ascertained from a computerised laboratory database or clinical notes, whilst associated laboratory features were obtained from the same sources.

The 125 IgM paraproteins detected constitute 19.7% of all new paraproteins observed over the period of study. IgM paraproteinaemia occurred more commonly in males and its frequency increased with age. Approximately 30% were associated with B cell lymphoproliferative disorders (Waldenstrom's macroglobulinaemia, non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, amyloid, etc.) with the remainder being labelled as monoclonal IgM gammopathies of uncertain significance (four having a peripheral neuropathy). At clinical presentation, patients with lymphoproliferative disorders tended to have higher levels of IgM, beta2-microglobulin, the presence of free urinary light chains and demonstrated molecular size heterogenicity of the paraprotein (presence of decamers, oligomers and monomers in addition to the pentamer) but there was considerable overlap. A good correlation was noted between paraprotein concentration and viscosity in most patients.

IgM paraproteinaemia was most frequently encountered in the context of a gammopathy of uncertain significance. Features which suggested lymphoproliferative disorders included higher levels of paraprotein (>15 g/l) elevated levels of beta2-microglobulin and the presence of urinary free high chain. However, as much overlap was seen, regular monitoring of paraprotein levels is considered mandatory in the management of these patients.