Rituximab-induced accelerated cryoprecipitation in hepatitis C virus-associated mixed cryoglobulinemia has parallels with intravenous immunoglobulin-induced immune complex deposition in mixed cryoglobulinemia: Comment on the article by Sène et al

摘要

To the Editor:Sene and colleagues' report of rituximab-induced accelerated cryoprecipitation causing a severe flare of hepatitis C virus-associated mixed cryoglobulinemic vasculitis or serum sickness (1) makes fascinating reading because of its similarities with intravenous immunoglobulin (IVIG)-induced reactions in patients with type II cryoglobulinemic vasculitis.Sene and colleagues contend that the IgM paraprotein containing rheumatoid factor (RF) in type II cryoglobulins forms a complex with rituximab, an IgGlK chimeric antibody, which then leads to immune complex deposition in multiple sites, including the kidneys and skin. In support of their hypothesis, they provide persuasive evidence from immunodot assays and Western blots that only sera containing RF activity (from patients with either mixed cryoglobulinemia or RF-positive rheumatoid arthritis [RA]) are capable of binding to rituximab IgGlK or, similarly, to infliximab IgGlK. In order to strengthen their hypothesis, it would be interesting to ascertain whether serum from mixed cryoglobulinemia patients who tolerated rituximab also reacted in a similar way.If this hypothesis is correct, it is likely that iatrogenic worsening of type II cryoglobulinemic vasculitis will be seen if these patients are treated with other IgGl monoclonal antibodies or standard pooled IVIG. While there have been no reports of the former, there are a number of reports attesting to the risks of IVIG-induced serious adverse reactions in patients with type II cryoglobulinemia, due to the formation of immune complexes between the RF-containing IgM paraprotein, and the exogenous IgG and the consequent deposition in the skin and kidneys (2-4), as seen in the cases described by Sene et al.