Hepatitis C virus infection and type II cryoglobulinemia: An immunological perspective

Abstract

A striking feature of EMC discovered 20 years before the Hepatitis C Virus Infection and discovery of HCV was that monoclonal RF from different patients with the disease were identical as determined by Type II Cryoglobulinemia: An typing with an antibody that reacted with an epitope in the antigen-combining site of the RF called a ''cross-idiotype. '' 6 Immunological Perspective It was subsequently shown that these monoclonal RF were encoded by the same germline genes.7 Hence, the monoclonal RF in these patients were highly restricted, rather than arising VINCENT AGNELLO randomly from the entire antibody repertoire. Among patients with HCV infection and type II cryoglobulinemia, 87% From an immunological perspective, the first clinical man-had monoclonal RF of the same cross-idiotype, 8 dubbed ifestation of hepatitis C virus (HCV) infection that attracted ''WA'' after the patient whose monoclonal RF was used to attention was palpable purpura. Thirty years ago, Meltzer raise the original typing antiserum.6 These findings suggested et al. described essential mixed cryoglobulinemia (EMC). 1 that the WA monoclonal RF in different individuals arose Palpable purpura was the prominent manifestation of this from stimulation with the same antigen and not a malignant systemic vasculitic disorder associated with mixed cryo-process, as was previously proposed.9 Moreover, the later globulins that consisted of polyclonal immunoglobulin (Ig) demonstration of the specific concentration of HCV in the G and either polyclonal or monoclonal (IgM) rheumatoid cryoglobulins with WA monoclonal RF 3 suggested that the factors (RF). The mixed cryoglobulins were later categorized etiologic antigen for production of these RF was related to as type II if the RF was monoclonal and type III if polyclonal the HCV. RF was present. It has been recently shown that approxiThere are three major immunological features associated mately 80% of patients with EMC are infected with HCV, 2 with this enigmatic virus. The first and most important is that and that the virus is specifically concentrated in the cryo-the virus, in almost all instances, circumvents the immune globulins.3 Earlier studies had implicated hepatitis B virus in response, with chronic infection as the result. The second EMC, 4 but it is now established that hepatitis B virus is feature, the occurrence of restricted monoclonal RF, may be unique to HCV infection, because monoclonal RF associated present in relatively few patients with the disease. Abbreviations: HCV, hepatitis C virus; EMC, essential mixed cryoglobulinemia; Ig, immunoglobulin; RF, rheumatoid factors; MPGN, membranous proliferative glomerulonephritis; ISH, in situ hybridization; VLDL, very-low density lipoprotein.

Characterization of Low- and Very-Low-Density Hepatitis C Virus RNA-Containing Particles

“…However, because of the small amount of material available, we have not yet determined the specificities of these antibodies. For the same reason, we do not know whether IgM antibodies present in these complexes are directed to viral structures or are monoclonal or polyclonal IgM anti-IgG antibodies; the latter would provide an explanation for the high frequency of cryoglobulinemia observed in chronically infected patients (1).…”

“…Two cell surface receptors, the LDL receptor and CD81, interact with HCV and HCV envelope protein E2, respectively, leading to the hypothesis that they both act as viral receptors (28,30,31,40). Although several reports have shown a highly specific interaction between HCV E2 and cellular CD81 (31), most recent studies have indicated that putative lipoprotein-associated HCV particles may infect cells via the LDL receptor (1,44). Characterization of this pathway has become challenging, especially since it appears to be preferentially active on hepatocytes.…”

Differential regulation of SOCS‐1 signalling in B and T lymphocytes by hepatitis C virus core protein

“…Over 90% of individuals with mixed cryoglobulinemia are found to have HCV infection. 24,25 Mixed cryoglobulinemia is the major extrahepatic manifestation of HCV infection and is found in 30-50% of HCV patients, who also have a high prevalence of non-Hodgkin B-cell lymphoma. [26][27][28][29] Investigators have suggested that persistent HCV antigen may stimulate crucial cell signalling pathways, leading to T-cell-dependent B-cell expansion and predisposing the patient to autoimmune and lymphoproliferative disorders.…”

Increased serum levels of the chemokine CXCL13 and up-regulation of its gene expression are distinctive features of HCV-related cryoglobulinemia and correlate with active cutaneous vasculitis

“…32 A more frequent formation of intraportal lymphoid follicles in MC patients compared with patients without MC has been reported. 33 It is assumed that these structures contribute to antigen presentation in situ, to clonal expansion of antigenspecific B and T cells, and to switching of an acute inflammation into a chronic one. 34 In this study, CXCL13 expression was recognized in the liver of MC patients with morphologic pictures of follicle-like structures, suggesting its major role in the organization and maintenance of For personal use only.…”