Organ-specific autoimmunity and genetic predisposition in interferon-treated HCV-related chronic hepatitis patients.
OBJECTIVE
Interferon alpha has been reported to enhance autoantibody production and to increase the risk of autoimmunity particularly against thyroid tissue. We designed a study with the following aims: 1) to assess the incidence of organ- and non-organ-specific autoantibodies during Interferon treatment; 2) to evaluate whether these autoantibodies have any clinical relevance; 3) to establish whether the development of autoimmune disorders can be related to a genetic predisposition.


METHODS
A panel of 5 non-organ-specific and 6 organ-specific autoantibodies was evaluated in serum samples collected before treatment and then at 3 and 12 months in 47 patients enrolled in a treatment protocol with a 2b-recombinant Interferon (3 MU, 3 times a week for 12 months). In the second part of the study we explored genetic predisposition for autoimmune disorders in 31 patients by DNA-HLA class II typing using Restriction Fragment Length Polymorphism (RFPL).


RESULTS
Non-organ-specific autoantibodies were absent in all patients before and after Interferon. During follow-up 6 patients showed an increment in thyroid microsomal antibody titres; 3 of these also developed thyroglobulin autoantibodies; 3 of the 6 patients developed persistent hypothyroidism; a fourth had a transient subclinical hypothyroidism and a fifth had a transient subclinical hyperthyroidism. Two patients with initial positivity for ICA and PCA maintained their reactivity during treatment without impairment of the respective target organs. Eight out of 39 initially negative patients developed one or more organ-specific autoantibodies during follow-up. One of these developed a persistent hypothyroidism, and another developed insulin-dependent diabetes. HLA-typing did not reveal any particular allele frequency in patients with thyroid antibody positivity as compared with those without autoantibodies and controls. Moreover, four of the 6 patients positive for islet-cell antibodies were carrying the non-Asp 57 allele which is considered a marker of a genetic predisposition for insulin-dependent diabetes.


CONCLUSIONS
These findings suggest that, besides the thyroid gland, pancreatic beta-cells could be a target of autoimmunity during Interferon-treatment for chronic HCV hepatitis. A genetic predisposition may be important, though insufficient alone, in the development of Interferon-induced autoimmune phenomena.
Floreani
A
A
Dept. of Gastroenterology, University of Padova, Italy.
Chiaramonte
M
M
Greggio
N A
NA
Fabris
P
P
De Lazzari
F
F
Naccarato
R
R
Betterle
C
C
D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D001323:Autoantibodies / Q000032:analysis*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005500:Follow-Up Studies; D006526:Hepatitis C / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000032:analysis; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011446:Prospective Studies; D011994:Recombinant Proteins; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology
D000998:Antiviral Agents; D001323:Autoantibodies; D018937:Hepatitis C Antibodies; D000949:Histocompatibility Antigens Class II; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004247:DNA; D013954:Thyroglobulin