Serological markers of autoimmunity in renal transplant patients with chronic hepatitis C.
Rostaing L. Modesto A. Cisterne JM. Izopet J. Oksman F. Duffaut M. Abbal M. Durand D.
Multiorgan Transplant Unit, Toulouse University Hospital, France.
The aims of this prospective study were to assess the frequency of serological markers of autoimmunity and cryoglobulins in renal transplant (RT) patients presenting with chronic hepatitis C, and to correlate them with serum alanine aminotransferase (ALT) levels, hepatitis C virus (HCV) genotypes and viremia, and HLA-DR phenotypes. Three groups of patients were studied: group I comprised 74 HCV + ve RT patients; group II, 33 HCV-ve RT patients, and group III, 13 HCV-ve/hepatitis B virus (HBV)-positive RT patients. The three groups did not differ significantly according to their mean age, sex ratio and baseline immunosuppression. Serum specimens of these patients were tested for complement (hemolytic activity (CH50), C3, C4 and properdin factor B (PFB) components, rheumatoid factor (RF), immunoglobulin patterns, circulating immune complexes, and autoantibodies including antinuclear (ANA), anti-smooth muscle (ASMA), antimitochondrial, antithyroid microsomal (ATM), antithyroglobulin (ATG) and anti-LKM1 autoantibodies. We also looked for the presence of cryoglobulins in groups I and III. Cryoglobulinemia of type II was present in 2 patients of group I (2.7%) which was associated in 1 case with de novo membranoproliferative glomerulonephritis but was not found in any of the patients of group III. RF (> 40U/ml) were more frequently observed in groups I (55.4%) and III (46%) than in group II (20.6%), although the difference was not statistically significant (p = 0.06). Oligoclonal or monoclonal serum immunoglobulin patterns were present in 16.2% of the patients in group I, 15.4% in group III and only 3.3% in group II (p = 0.07). There was no significant difference between the prevalence of at least one autoantibody in the three groups (ranging from 38.5 to 50%), and neither was the frequency of ANA (23-36.6%), even at a high titer i.e. above 1:320, or ASMA (13.5-23%) significantly different. Conversely, tissue-specific autoantibodies, i.e. ATM, ATG and anti-LKM1, were only observed in HCV+ve patients. CH50, C3, C4 and PFB levels were significantly lower in group I than in group II, although values below the normal ranges were observed only for CH50 and C3 and were mostly found in the HCV+ve RT patients. Circulating immune complexes detected by nephelometry were at similar levels in the three groups, within the normal ranges. The occurrence of at least one autoantibody and/or the presence of RF > 40 U/ml did not correlate with either serum ALT levels or a given HLA-DR phenotype in any of the three groups, nor did they correlate with HCV genotype or HCV viremia in group I. In conclusion, this study shows that contrary to HCV+ve immunocompetent patients, HCV+ve RT patients rarely present with cryoglobulinemia and have the same frequency of non-organ-specific autoantibodies as HCV-ve RT patients. Conversely, antithyroid autoantibodies are only observed in the former group. Finally, serological markers of autoimmunity are not related to serum ALT levels, HLA-DR phenotype, HCV viremia or HCV genotype in HCV+ve RT patients.