Immunosuppressive effects of factor IX products: an in vitro study

The effects of a recombinant factor IX product (BeneFix), and of five plasm a-derived factor IX products, AlphaNine, Immunine, Konyne, Mononine and Rep linine on in vitro peripheral blood mononuclear cell (PBMC) immune function were compared in a blinded study. We assessed the effects of these product s on Con-A-induced lymphocyte proliferation and interleukin-2 and interleuk in-10 secretion, expression of lymphocyte activation markers, and nitric ox ide secretion by stimulated mouse peritoneal macrophages. At 1 mL(-1) for 4 8 h, Konyne reduced Con-A-induced mitogenesis by 50% (P < 0.05); AlphaNine, Mononine and BeneFix had no effect. At 10 IU mL(-1), Con-A-induced mi- tog enesis was at control levels with Mononine and BeneFix, but was reduced to < 15% (P < 0.05) with each of the other products. IL-2 and IL-10 secretion by Con-A-stimulated lymphocytes was also markedly depressed by all the prod ucts tested except Mononine and BeneFix. Dialysis of these products did not substantially affect these results. Flow cytometric analysis of lymphocyte activation markers following Con-A stimulation showed that Konyne also dec reased IL-2 receptor alpha and beta chain (CD25 and CD122) induction on PBM C. Konyne also inhibited nitric oxide secretion to levels < 18% of controls . These results indicate that certain factor IX products, including some of purported higher purity, substantially depress in vitro immune function. T he importance of these findings to in vivo immune function in haemophilia B patients remains to be established.