Hepatitis C Virus Infection and Mixed Cryoglobulinemia

Abstract

<jats:p>Hepatitis C virus (HCV) chronic infection is recognized as the major cause of mixed cryoglobulinemia (MC). Its persistence represents a continuous stimulus for host immune system with production of circulating immune complexes (ICs), one-third of them with cryoprecipitate property. Several factors contribute to the biological activities of ICs, many of which are not completely known. Among them, complement factors play a crucial role in the cold-insoluble ICs-mediated vasculitis, involving primarily small blood vessels in different tissues including skin, kidney, peripheral, and central nervous system. Liver represents the major target of HCV infection with inflammatory infiltrates, resembling secondary lymphoid follicles. Cytokine like CXCL13 contribute to B-cell homing in intraportal lymphoid aggregates, in which B-cell clonal selection may arise. B-cell clonal expansion starts as an antigen-driven event and expands towards indolent and malignant B-cell proliferation. Occurrence of intrahepatic B-cell clonalities correlates with extrahepatic clinical manifestations of HCV infection. In this context, cryoglobulinemic patients should be considered a peculiar HCV-infected population that needs a clinical multidisciplinary approach and more articulated therapeutic measures.</jats:p>

The etiology of glomerulonephritis: roles of infection and autoimmunity

“…113 It involves pathways similar to those described above for EBV virus and SLE, including strong activation of the innate immune system through TLRs, a viral gene signature pattern, B-cell clonal expansion, and defects in the complement system. 117,118 In fact, in both clinical and renal pathologic manifestations, SLE and type I MPGN have much in common. In MPGN I, both IgM and IgG rheumatoid factors (type II cryoglobulins) are present in 70-80% of patients, C3Nefs are seen in 20-30% of patients, and antiendothelial cell antibodies have been reported as well, thus documenting the existence of autoimmunity in HCVassociated MPGNI.…”

Principles of Separation

“…Complications may include hyperviscosity syndrome. Pegylated IFN-a and ribavirin are now considered the standard of care for hepatitis C management, the major cause of mixed cryoglobulinemia (40). The addition of TPE allows efficient removal of cryoglobulins, and may also improve immune complex solubility by altering the antigen-antibody ratio (41).…”

Non-Anti-Neutrophil Anti-Cytoplasmic Antibodies Associated Methimazole-Induced Nephritis: Case and Review of Literature

“…There was no evidence of cryoglobulin-associated glomerulonephritis. Furthermore, the most common cause of cryoglobulinemia is hepatitis C infection [13] and serology was negative in our patient. Also, the possibility of hypergammaglobulinemia and hypocomplementemia were considered as other potential causes of interstitial nephritis.…”