Anticardiolipin Antibodies in Patients with Chronic Hepatitis C Virus Infection: Characterization in Relation to Antiphospholipid Syndrome

Abstract

The antiphospholipid syndrome (APS) is usually defined by the association of clinical manifestations that comprise venous and/or arterial thrombosis, recurrent fetal losses, and thrombocytopenia, along with the presence of anticardiolipin (aCL) antibodies and/or lupus anticoagulant. Various infectious diseases can induce aCL; however, these antibodies are not usually associated with thrombotic events, as happens with autoimmune diseases, in which these antibodies need the presence of ␤ 2 -glycoprotein I. Levels of immunoglobulin G (IgG) and IgM aCL antibodies were determined by enzyme-linked immunosorbent assay for 243 patients with chronic hepatitis C virus (HCV) infection and 100 healthy controls. Clinical events of APS, the level of ␤ 2 -glycoprotein dependence of aCL, the presence of cryoglobulins and other autoantibodies, and cross-reactivity between purified aCL and HCV were evaluated. Positive results for aCL antibodies were found more frequently (3.3%) for the patients with HCV infection than for healthy controls (0%). All positive aCL antibodies were ␤ 2 -glycoprotein I independent. No significant association was found between aCL antibodies and clinical manifestations of APS, neither was one found between the presence of other autoantibodies or cryoglobulins and that of aCL. Finally, no cross-reactivity between aCL antibodies and HCV antigens was observed. As previously reported, aCL antibodies seem to be an epiphenomenon, and they do not have clinical or laboratory significance in HCV patients.Infection with hepatitis C virus (HCV) may lead to an autoantibody response. It has been reported that chronically infected HCV patients have anti-smooth muscle antibodies, rheumatoid factor, anti-liver-kidney-microsomal (aLKM) antibodies, anticardiolipin (aCL) antibodies, and low titers of antinuclear antibodies (ANA) (1,6,8,31).Antiphospholipid (aPL) antibodies, such as aCL and lupus anticoagulant (LA), are a group of antibodies with an apparent affinity for anionic phospholipids. New data indicate that the antigenic targets of aPL detected in conventional aCL and LA assays are phospholipid-binding plasma proteins, most notably ␤ 2 -glycoprotein I (␤ 2 GPI) and prothrombin, or complexes of these proteins with phospholipids (28). aPL antibodies are detected in patients with autoimmune and infectious diseases and other conditions. In patients with autoimmune diseases, they have been associated with thrombosis, thrombocytopenia, fetal loss, and a variety of other clinical manifestations (livedo reticularis, valvular heart disease, etc.). This clinical association has been defined as antiphospholipid syndrome (APS) (2, 11). In this syndrome, aCL antibodies require ␤ 2 GPI to bind cardiolipin, but aCL antibodies induced by infections do not usually require this cofactor to bind the anionic phospholipid and are considered nonpathogenic (21, 23).In previous studies, members of our group tested aCL antibodies and their cofactor dependence in sera from patients with infectious diseases such as syphilis, leprosy, human ...

Prevalence of Autoantibodies in Patients with Hepatitis C Virus Infection in Oman

“…The frequency of organ-specific autoantibodies in HCV patients included in our study is significantly lower than that of the non-organ specific autoantibodies, which could explain the systemic nature of the clinical syndromes associated with patients with HCV, which include rheumatic manifestations and systemic vasculitis, as suggested by other studies. 24,26,34,35 The prevalence of ACA among patients with chronic HCV has been investigated by other groups, who describe an ACA frequency among HCV patients ranging from 3-22%. 11,35,36 Our results fell within this range.…”

“…24,26,34,35 The prevalence of ACA among patients with chronic HCV has been investigated by other groups, who describe an ACA frequency among HCV patients ranging from 3-22%. 11,35,36 Our results fell within this range. The wide range of ACA reported by different groups may be explained by differences in methodology.…”

Relationship between Autoimmunity and Cancer or Metabolic Abnormality in Liver Diseases

“…8OHdG is well recognized as oxidatively generated DNA damage [80], implying that the emergence of anti-cardiolipin was associated with oxidative stress in those patients. However, none of the CH-C patients seropositive for anticardiolipin fulfilled the category for anti-phospholipid syndrome [79,[81][82][83][84]. It is of interest that anti-cardiolipin in patients with CH-C were in generally low titers, and were not associated with antibodies to 2-glycoprotein-I.…”

“…Antibodies to oxidatively modified autoantigens were also trapped in the sera of patients with NAFLD and chronic hepatitis C (CH-C). Titers of malondialdehyde (MDA)-adducted NAFLD correlation with hepatic fibrosis [73] anti-oxLDL oxLDL HCV correlation with hepatic steatosis [75] anti-SOD SOD AIH false-positivity for anti-HCV [78] anti-cardiolipin cardiolipin HCV correlation with oxidative stress [79] HCV higher prevalence of portal hypertension [86] HCV lack in the symptoms for anti-phospholipid syndrome [79,[81][82][83][84] HCV concurrent oral lichen planus [87] HCV concurrent mixed cryoglobulin [88] NASH N/A [79] AIH Indicator for more advanced liver fibrosis [89] PBC, PSC indicator for more advanced liver fibrosis [90] anti-CYP2E1 CYP2E1 halothene-induced hepatitis specific to IgG4 type of anti-CYP2E1 [101] alcoholic liver cirrhosis N/A [95,96] AIH N/A [97][98][99] HCV indicator for more severe necroinflammation [97,102] anti-HSP HSP65 AIH molecular mimicry between HSP and SOD [105] HSP70 PBC indicator for disease activity [106] HSP70 HCV inverse correlation with diseae-activity [108] human serum albumin (HSA) were elevated in CH-C patients with severe hepatic steatosis [72]. To the contrary, an increase in titers of antibodies to MDA-HSA was independently associated with the progression of liver fibrosis in patients with NAFLD [73].…”

Study of anticardiolipin antibody in hepatitis C virus-positive patients

“…HCV infection may lead to autoimmune response. It has been reported that chronically infected HCV patients possess anti-smooth muscle antibodies, rheumatoid factor, anti-liver-kidney-microsomal antibodies, anticardiolipin antibodies (ACA), and low titers of antinuclear antibodies (2). Interferon treatment of HCV infection may precipitate or exacerbate the associated autoimmune disease (3).…”