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Autoantibodies Present in Chronic Hepatitis C and Chronic Hepatitis B Viral Infections

HEPATOLOGY, May 1998, p. 1452-1452, Vol. 27, No. 5


To the Editor:

In a recent study reported by Cassani et al.,1 the overall prevalence of autoantibodies present in chronic Hepatitis C virus (HCV) infected patients was 30%. They tested for autoantibodies to nuclear antigens (ANA), smooth muscle (SMA), and liver/kidney microsomes 1 (LKM 1) as markers of autoimmune responses. Many patients with hepatitis present with clinical symptoms or evidence of autoimmunity, and the treatment can be misguided if the evidence is prevalent. Clifford et al.2 reported patients with chronic HCV with a remarkable association with this disease and other autoimmune disorders. Several reports of cryoglobulinemia have described the association with HCV infections.3 Clifford et al.2 reported that 91% of the HCV patients tested had autoantibodies to SMA and 76% had rheumatoid factor present, which is much more than that reported by Cassani et al.1 In our study, we evaluated the immune response to a variety of classic peptides which are commonly known extractable nuclear antigens and which have been defined by molecular weight using a Western blot method.

We tested banked frozen sera from 24 chronic HCV patients who were classified based on six months or more of the liver enzyme, alanine transaminase (ALT) elevation, and on proven serologic response to the current HCV recombinant peptides. In addition, banked frozen sera from 24 chronic Hepatitis B virus (HBV) infected individuals were also tested along with 40 normal, healthy blood donors. Chronic HBV patients were classified on the basis of presence of Hepatitis B surface antigen for six months or persistent HBV DNA over this period of time. The protocol for testing was approved by the Institutional Review Board at Baptist Regional Laboratories (Memphis, TN) and conformed to appropriate ethical standards.

The Western blots (Affini Tech LTD, Bentonville, AR) were performed according to manufacturer’s recommendations using an initial serum dilution of 1:50 in diluent made from phosphate buffered saline (pH 7.2) with 0.3% Tween 20 and 3% powdered milk. The antigen source for blot development was derived from Hep-2 cells. The initial incubation and the conjugated antiserum incubation each lasted one hour.

Specific autoantibodies to the defined peptides among HCV and HBV patients and controls are shown in table 1. In addition, autoantibodies to undefined peptides by occurrence and molecular weight of the respective peptides are depicted in table 2. These Hep-2 cell-line derived peptides are not yet characterized and specific patterns have not been defined. We observed an antibody to these proteins that could only be separated by molecular weight at this time. In addition, the occurrence of the antibodies to the undefined peptides is markedly greater than that in the normal controls ( table 2).

View This table table 1. Incidence of Antibodies to Defined Peptides Among HCV and HBV Patients
View This table table 2. Incidence of Antibodies to Undefined Peptides Among HCV and HBV Patients

Among the chronic HCV patients, numerous antibodies are present to defined and undefined peptides. Of special interest was the presence of antibodies to p105 in 54% of HCV patients, which is commonly seen in anti-Scl 70, and 83% of these patients had antibodies to p60 which can be seen in anti-Sjögren Syndrome-A. Of the HCV patients, 63% presented with positive responses to p86 which is a peptide associated with anti-Ku. Similarly, 58% of the chronic HBV patients had antibodies to p105 (Scl-70 peptide) but only 63% had antibodies to the p60 peptide. The HBV patients had a 46% positive rate against the same anti-Ku peptide (86 kd). In contrast, none of the healthy controls had antibodies to p105, only 23% had a single band to p60, and 3% had a positive response to the p86 peptide. Significant antibodies were noted among the other specified peptides in both HCV and HBV but not in the controls.

We confirmed that chronic HCV and HBV patients demonstrate the presence of autoantibodies to peptides which are not usually found in the healthy individual. Although HCV is an RNA virus in the flavivirus family and HBV is a DNA virus in the Hepadnaviridae family, both chronic infectious states appear to induce an autoimmune component. Neither the viral induction of autoimmune responses4nor the clinical evidence of autoimmunity in these infections is new.5 Abuaf et al.6 reported that 18% of chronic HCV patients had positive anti-nuclear antibodies compared with 3% among a normal blood donor population. However, the presence of significant autoantibodies may be misleading in diagnosis as many of these antibodies are thought to be found only in specific rheumatic or autoimmune diseases. The irregular patterns and the inconsistent findings among the patients suggest that the development of these autoantibodies are probably an epiphenomenon which is caused by tissue destruction and by the availability of protected proteins that are not normally seen by the individual’s immune system. However, in recent studies in which microbial infections triggered autoimmunity, the theory of molecular mimicry is suggested where some molecules of the microorganisms resemble those of the host.7 As the host mounts a defense against the infectious agent, it inadvertently activates immune responses against the host’s own molecules. Segal et al.7 further suggest that the production of interleukin (IL)-12 arouses the self-reactive immune cells. As Cassani et al.1 stated, further studies are needed to assess the relevance of autoimmune response development and symptoms and as well as infectious disease progression.

David L. Smalley, Ph.D

Baptist Regional Laboratories and Departments

;of Pathology and Clinical Laboratory Sciences

University of Tennessee

Mary F. Hall, B.S.

Baptist Regional Laboratories

Clifford L. Broughton, B.S.

Clinical Laboratory Sciences

University of Tennessee

Memphis, TN


1. Cassani F, Cataleta M, Valentini P, Muratori P, Giostra F, Francesconi R, Muratori L, et al. Serum autoantibodies in chronic Hepatitis C: comparison with autoimmune hepatitis and impact on the disease profile. HEPATOLOGY 1997; 26: 561-566[Abstract].

2. Clifford BD, Donahue D, Smith L, Cable E, Luttig B, Manns M, Bonkovsky HL. High prevalence of serological markers of autoimmunity in patients with chronic Hepatitis C. HEPATOLOGY 1995; 21: 613-619[Medline].

3. Agnello V, Chung RT, Kaplan LM. A role for Hepatitis C virus infection in type II mixed cryoglobulinemia. N Engl J Med 1992; 327: 1490-1495[Medline].

4. Garry RF. New evidence for involvement of retroviruses in Sjogren’s syndrome and other autoimmune diseases. Arthritis Rheum 1994; 37: 465-469[Medline].

5. Marazuela M, Garcia-Buey L, Gonzalez-Fernandez B, Garcia-Monzon C, Arranza A, Borque MJ, Moreno-Otero R. Thyroid autoimmune disorders in patients with chronic Hepatitis C before and during interferon- therapy. Clin Endocrinol 1996; 44: 635-642[Medline].

6. Abuaf N, Lunel F, Giral P, Borotto E, Laperche S, Poupon R, Opolon P, et al. Non-organ specific autoantibodies associated with chronic C virus hepatitis. J Hepatol 1993; 18: 359-364[Medline].

7. Segal B, Klinman DM, Shevach EM. Microbial products induce autoimmune disease by an IL-12 dependent pathway. J Immunol 1997; 158: 5087-5090[Medline].

Copyright © 1998 by the American Association for the Study of Liver Diseases.