Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from patients with essential mixed cryoglobulinemia

Peripheral blood mononuclear cells from patients with essential mixed cryoglobulinemia (EMC) were studied for their ability to differentiate into cells containing cytoplasmic immunoglobulins (Ig) and to synthetize Ig after in vitro pokeweed mitogen activation. EMC lymphocytes showed a significant defective differentiation and Ig synthesis compared to normal controls. Coculture experiments carried out mixing enriched normal T- and EMC B-cell suspensions, and vice versa, showed that (a) the EMC B-cell-defective Ig synthesis still persisted after removal of suppressor activity by irradiation, both with autologous and with normal allogeneic T suspensions and (b) EMC T cells displayed a less efficient activity in helping Ig production by normal B lymphocytes. A comparable, reduced response was also found after activation with Staphylococcus aureus strain Cowan I. Taken together these results seem to indicate that in essential mixed cryoglobulinemia an impaired T-cell helper activity coexists with a B-lymphocyte impairment. The significance of these abnormalities in the pathogenesis of EMC is discussed.