{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T05:52:16Z","timestamp":1760853136250},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,9,22]],"date-time":"2005-09-22T00:00:00Z","timestamp":1127347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2006,3]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold> Hepatitis C virus (HCV) plays a major role in the induction of type II mixed cryoglobulinaemia (MCII). The role of HCV proteins and virus\u2013host interaction in the pathogenesis of MC remains to be defined. To address this issue, we have characterized, in detail, the monoclonal IgM and the viral component of circulating immune complexes in eight patients with HCV\u2010associated MCII. The proportion of HCV\u2010RNA compartmentalized in the cryoprecipitate (CP) varied greatly (10\u201380% of total HCV\u2010RNA). The complementary determining region (CDR)3 sequences of monoclonal immunoglobulin M (IgM) V<jats:sub>H<\/jats:sub> and V<jats:sub>K<\/jats:sub> genes were highly homologous to rheumatoid factor and to antibodies against HCV\u2010E2. Furthermore, the CDR3 sequences in some of our MCII patients were highly similar to those described in HCV\u2010positive patients with non\u2010Hodgkin's lymphoma (NHL). From these results, it appears that, as in the case of NHL, the IgM\u2010rheumatoid factor (RF) production in MCII patients is antigen driven, namely by E2. However, the limited number of mutations in V<jats:sub>H<\/jats:sub> and V<jats:sub>K<\/jats:sub> genes with respect to the germline and their distribution showed that the B\u2010cell response in these cases was prevented from undergoing affinity maturation. Furthermore, in patients with monoclonal IgM and definite compartmentalization of HCV in either CP or supernatant, a highly homogeneous E2\u2010hypervariable region (HVR)1 sequence distribution was found (90\u2013100% identical clones), a feature of the quasispecies frequently associated with an impaired humoral immune response to HCV. These findings suggest that in patients with HCV\u2010associated MCII, maturation of monoclonal B lymphocytes may be blocked in a primitive stage preventing serious damaging effects because of the auto\u2010reactivity of their secreted immunoglobulins.<\/jats:p>","DOI":"10.1111\/j.1365-2893.2005.00675.x","type":"journal-article","created":{"date-parts":[[2005,9,22]],"date-time":"2005-09-22T15:07:17Z","timestamp":1127401637000},"page":"166-176","source":"Crossref","is-referenced-by-count":12,"title":["Detailed analysis of the E2\u2013IgM complex in hepatitis C\u2010related type II mixed cryoglobulinaemia"],"prefix":"10.1111","volume":"13","author":[{"given":"S.","family":"Ferri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Dal Pero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Bortoletto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. 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