The nature of the B-cell subsets associated with chronic hepatitis C virus related type II mixed cryoglobulinemia (HCV-MC) is unclear. We report the case of a 64-year-male with acute onset wrist drop and foot drop, secondary to HCV-MC related mononeuritis multiplex, who was treated with rituximab, an anti-CD20(+) antibody directed against B cells. We monitored the frequency of B-cell subsets in peripheral blood before and after rituximab, and correlated B-cell subset changes with clinical response. Significant improvements in his wrist and foot drop, as well as his vasculitic rash, depression and erectile dysfunction were evident within six days of starting rituximab and have persisted several months after B-cell recovery. More than 95% of CD20(+) B cells had disappeared from peripheral blood within 1 week, returning to baseline by week 21. CD20(+)CXCR3(+) frequency at baseline was similar to that at week 21. CD20(+)CD5(+), the human equivalent of B1 B cells and CD20(+)IgM(+)IgD(+), naïve B cells were increased. By contrast, CD20(+)CD27(+) memory cell frequency was reduced. These data suggest that CD27(+) memory B cells, but not CD5(+) and IgM(+)IgD(+) B cells may play a role in the clinical manifestations of cryoglobulinemia.
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