FAMILIAL MACROGLOBULINEMIA - HYPERACTIVE B-CELLS BUT NORMAL NATURAL-KILLER FUNCTION

An Icelandic family with two cases of benign monoclonal gammopathy and one case each of Waldenstrom's macroglobulinaemia, histiocytic lympho ma and multiple myeloma was first described in 1978. Nine family membe rs had then shown raised values for se-IgM. Of these one has since die d and another was not available for testing. In four of the remaining seven se-IgM had returned to normal; the three subjects who still show ed raised se-IgM included the case of multiple myeloma diagnosed in 19 85. Baseline production of IgM, IgG and Ig in vitro was normal in the 35 family members studied compared with 13 healthy control subjects, b ut the mean production of all immunoglobulin classes in response to mi nimal stimulation with PWM (1 mu g/ml) was significantly increased (P < 0.05). Ten family members showed markedly increased production of al l three immunoglobulin classes (> 3 x SD above mean for controls). Rai sed production of IgM never occurred alone, indicating intact class sw itching. One family member showed extremely high values: IgA: 5.15 mu g/ml, IgG: 16.3 mu g/ml, IgM: 24.8 mu g/ml (means for controls: 0.066, 0.123, 0.185 respectively). These 10 family members were of both sexe s, ranged in age from 16 to 84 years and were clustered mainly in thre e distinct groups within the pedigree suggesting heredity. Proliferati ve responses to PWM were not significantly increased. Serum levels of interleukin-4 were tested in the patient with multiple myeloma and the family member with highest Ig production and found to be normal. We f ound no evidence for depressed NK function. Thus, in this family with a tendency for macroglobulinaemia and B cell derived malignancies B ce ll hyperreactivity was detectable by in vitro testing in several asymp tomatic family members, of both sexes and all ages. No evidence was ob tained for defects in regulatory mechanisms.