Influence of factor substitution on the B-cell response in hemophiliacs

Studies in hemophiliacs receiving factor concentrates demonstrated T-cell defects in vitro. Recently, B-cell dysfunctions were described in AIDS and pre-AIDS and in some hemophiliacs. To investigate the B-cell function in hemophiliacs in relation to factor substitution, we examined five patients with mild (substitution less than 20,000 U/year) and seven with severe (greater than 100,000 U/year) hemophilia A and compared the data with normal control individuals. The B-cell proliferative response (3H-thymidine uptake) to Staphylococcus aureus Cowan I and the differentiation response (Ig secretion into culture supernatants) to T-cell-dependent or -independent polyclonal B-cell activators (PBAs) were studied in vitro. In contrast to T-cell dysfunctions, which correlate with the amount of clotting factor concentrates, the B-cell proliferative response was not affected. Stimulation with PBAs however failed to increase elevated spontaneous IgG levels and showed a diminished increase in IgM levels in severe, but not in mild, hemophilia. Our data give evidence of a T-cell-independent B-cell dysfunction in asymptomatic hemophiliacs that correlates with factor substitution.