A seroimmunological profile of erosive hand osteoarthritis.

OBJECTIVES: erosive hand osteoarthritis (EHOA) is an inflammatory disorder involving joints of the hands, which may be accompanied by acute phase reactants. The relationship between EHOA and classical osteoarthritis (OA) is still controversial, since some authors consider EHOA as a distinct disease, other as a subset of OA, and some as a border entity between OA and rheumatoid arthritis (RA). Scarce data are available about the seroimmunological profile of the disease, which could aid to identify a possible role of the immune system in EHOA pathogenesis, and could also allow to better differentiate EHOA both from OA and RA. MATERIAL AND METHODS: blood was drawn from the following patients: 37 with EHOA, 35 with OA and 45 with RA. All sera were tested for rheumatoid factor, anti-cyclic citrullinated peptide antibodies (anti-CCP), antinuclear antibodies (ANA), anti-extractable nuclear antigens (anti-ENA) and anti-neutrophil cytoplasmic antibodies (ANCA). RESULTS: ANCA were never detected in OA, whereas they were found in 7 (19%) EHOA and 8 (18%) RA patients; the difference between EHOA and OA was statistically significant (p<0.01). Anti-CCP antibodies, which were consistently negative in OA, were positive in 2 EHOA (5%) at a low titre and in 23 (51%) RA patients, usually at a very high titre. The difference between EHOA and OA was not statistically significant, while the number of RA positive patients was significantly higher (p<0.001). CONCLUSIONS: our findings suggest that the seroimmunological profile of EHOA is different from that of OA. In EHOA patients ANCA and anti-CCP antibodies might be either markers of inflammation involving neutrophils and/or markers of an underlying autoimmune process.

Autoimmune liver disorders and small-vessel vasculitis: four case reports and review of the literature.

Autoimmune liver diseases (AILD) are a group of immunologically induced hepatic disorders that can lead to liver cirrhosis and end-stage liver disease. Extra-hepatic involvement and association with rheumatic diseases (such as Sjögren's syndrome, systemic sclerosis and rheumatoid arthritis) are well known, whereas the coexistence of AILD with small-vessel vasculitis in the same patients have been only occasionally reported. In the present paper we report four such cases and an extensive review of the literature. Clinical features of autoimmune-liver diseases associated with small-vessel vasculitis are discussed, as well as possible common pathogenic pathways including HLA genomics, costimulatory molecules and autoantibodies. In conclusion, knowledge about this association can help physicians in recognising and treating an aggressive disease which could otherwise result in severe and multiple organ damage, compromising the overall prognosis and the indication to liver transplantation.

Etanercept and infliximab induce the same serological autoimmune modifications in patients with rheumatoid arthritis.

Etanercept and infliximab treatments are often associated with autoantibodies induction. Their reported prevalences vary among different studies and the conclusions are somehow conflicting, mainly regarding whether the two drugs induce the same modifications. In this small prospective study, specifically designed to identify transient phenomena, we assess the prevalence of different relevant rheumatologic autoantibodies during anti-TNF-alpha courses in patients with rheumatoid arthritis. We report that both etanercept and infliximab transiently induce anti-DNA antibodies in 50-78% of patients, respectively, and these antibodies seem to be different from the typical lupus associated ones. Antinuclear antibodies (ANA) increased their titres and were newly produced up to 100% of patients. No other relevant antibodies are affected. Finally, as also confirmed for the first time by the patients switched from one drug to the other, the two TNF-alpha blockers behave similarly.

Detection of HCV antigens in liver graft: relevance to the management of recurrent post-liver transplant hepatitis C.

The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive hepatocytes >/=50% as the only independent predictor for nonresponse (P < 0.001) in 26 patients treated with alpha-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment.

Detection of recipient's cells in liver graft using antibodies to mismatched HLA class I antigens.

Engraftment by recipient's (R) cells has been already demonstrated in gender mismatched liver grafts using fluorescence in situ hybridization (FISH), with contrasting results concerning epithelial cells. Mismatch for human leukocyte antigen (HLA) class I (HLA-I) is quite common in patients with orthotopic liver transplantation (OLT). We thus aimed to assess whether monoclonal antibodies (MoAbs), currently employed in the HLA typing process, could be used to study the dynamics of R cells in liver grafts. A total of 50 frozen liver biopsies from 37 patients receiving a HLA mismatch liver were tested. Biopsies were obtained from 3 days to more than 360 days after OLT. Frozen sections of graft biopsies were stained using an immunoperoxidase technique with the proper MoAbs. In selected cases, a double immunofluorescence was also performed. Circulating R blood cells and sinusoidal cells were occasionally observed in liver biopsies obtained within 10 days after OLT and were commonly detected after 1 month. The number of sinusoidal cells continued to increase up to 6 months, as shown on serial biopsies. On the whole, R blood cells and R sinusoidal cells were detected in 86% and 82% of the biopsies, respectively. R hepatocytes and biliary cells were detected after 40 and 60 days after OLT, respectively, in 14% (hepatocytes), 8% (bile ducts), and 12% (proliferating bile ducts) of the biopsies. R hepatocytes presented as single cells or groups of few cells; their number was lower than 1% and apparently did not increase with time after OLT. In conclusion, it is possible to detect R cells in liver graft using MoAbs to specific mismatched HLA-I alleles. R sinusoidal cells start to appear after 10 days and are commonly observed after 1 month; bile duct cells and hepatocytes appear later and their number does not increase with time. Engraftment by R epithelial cells seems to be less important than previously reported.