Reversion of anergy signatures in clonal CD21low B cells of mixed cryoglobulinemia after clearance of HCV viremia

Martina Del Padre, Laura Todi, Milica Mitrevski, Ramona Marrapodi, Stefania Colantuono, Massimo Fiorilli, Milvia Casato and Marcella Visentini

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  • RE: Fate of mixed cryoglobulinemia after elimination of HCV viremia
    • Morgan L McLemore, assistant Professor of Hematology Dept. of Hematology and Medical Oncology, Emory University, Atlanta
    • Other Contributors:
      • Manila Gaddh, assistant Professor of Hematology
      • Imre Bodó, Associate Professor of Hematology

    To the Editor:

    Most cases of mixed cryoglobulinemia result from chronic stimulation of the immune system by hepatitis C (HCV) viral antigens. Modern antiviral therapy is able to eradicate viral load in a significant portion of patients with HCV infection. However, the effect of stopping antigenic stimulation on the mixed monoclonal and polyclonal lymphoproliferation is not well known. Del Padre and colleagues1 provide new insight into the fate of clonal CD21low B cells after HCV clearance in 24 patients with HCV-associated cryoglobulinemia. However, they do not describe the fate of cryoglobulins themselves - as clinicians, we feel that the mechanism and the outcome are equally important.

    Clearance of HCV particles does not always result in elimination of cryoglobulins. Recently published studies2-7 with direct antiviral agents (DAA), reported variable (in aggregate 56%) cryoglobulin elimination after viral eradication (Figure 1, panel A).

    Most studies had relatively short follow-up, and suggested continued improvement of cryoglobulinemic status after viral eradication. In contrast, we present a 60-year old male patient with end-stage renal disease from HCV-associated cryoglobulinemic glomerulonephritis, on dialysis. The patient also had cutaneous vasculitis, arthritis and a multifactorial anemia requiring plasma exchanges (PEX)...

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    Conflict of Interest:
    None declared.