Anti-endothelial cell antibodies (AECA) in systemic sclerosis--increased sensitivity using different endothelial cell substrates and association with other autoantibodies.

OBJECTIVE: One of the main features of systemic sclerosis (SSc) is vascular damage, the mechanism of which is not understood. In the present study we examined whether screening of SSc patients for different anti-endothelial cells antibodies (AECA) of various origins increase the sensitivity of AECA detection in SSc patients. Secondary aim was an attempt to correlate AECA with other common autoantibodies. MATERIALS & METHODS: 478 SSc patients were studied for the presence AECA, anti-cardiolipin (aCL), anti-dsDNA, anti-heparin (AHA), anti-pyruvate dehydrogenase (PDH) and anti-PDC-E2 autoantibodies. AECA levels were detemined using human umbilical vein EC (HUVEC), bone marrow EC (BMEC), EC hybridoma (EA.hy 926) and Kaposi sarcoma EC (KS). RESULTS: Positive AECA were found in 49.5% of SSc patients (27.1% HUVEC; 34.3% BMEC; 26.3% EaHy 926 and 22.7% KS). The highest percent reactivity of AECA was obtained using microvascular BMEC. When combining BMEC and either other cell lines the reactivity ranged from 41.4% to 46%. A significant association between AECA on the one hand and AHA (p<0.001)) and anti-PDH (p<0.05) on the other was secn. Cross-reactivity with anti-PDC-E2 was excluded by inhibition tests, but AHA and anti-PDH may be part of the spectrum of AECA. CONCLUSIONS: Since false-negative AECA may result from lack of expression of various antigens on a specific EC, analysis of AECA in SSc patients requires using several EC types, including microvascular EC.

Linseed oil suppresses the anti-beta-2-glycoprotein-I in experimental antiphospholipid syndrome.

The immunomodulatory potential of a diet enriched with n-3 polyunsaturated fatty acids was analysed in naïve mice with experimental antiphospholipid syndrome (APS) induced by active immunization with H-3, a human anti-beta-2-glycoprotein-I (anti-betaGPI) monoclonal antibody (mAb). Fetal loss and other clinical manifestations of APS were prevented in the group of APS mice upon exposure to the enriched n-3 diet compared to the control group. The titers of anti-betaGPI were significantly lower (in O.D. at 405 nm, 1.387+/-0.232 in comparison to non-treated mice 0.637+/-0. 111, P< 0.05). The reduced titer of anti-betaGPI antibodies in the sera of the treated mice was associated with a reduced number of anti-betaGPI forming cells in cultured splenocytes (84+/-14, antibody-forming cells (AFC)/10(5)cells in comparison to 37+/-4 AFC/10(5)cells (P< 0.02).In addition to the suppression of the humoral response in mice with experimental APS fed with linseed oil, we also observed an inhibitory effect on the cellular response. The T-cell response to anti-betaGPI was lower in comparison to mice immunized with H-3 anti-betaGPI mAB, which were kept on a normal diet. These results indicate that polyunsaturated fatty acids may improve clinical and laboratory parameters of APS. The beneficial effects of diets enriched with n-3 should be further examined as a potential mode of therapy for patients with APS.

Diagnosis and treatment of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease that predominantly occurs in middle-aged women of various ethnic and racial populations. The disease slowly progresses over decades and is supposed to be caused by immune reactions against host antigens. Histologically, it is characterized by inflammatory destruction of intrahepatic small bile ducts, subsequent fibrosis, and finally liver cirrhosis. It is more frequently diagnosed now than in the past probably because of a greater awareness of the disease. There is only week association of PBC with genetic markers. Liver function tests reveal an elevation of serum alkaline phosphatase and gamma-glutamyl transpeptidase levels with or without elevated aminotransferase levels. The hallmark of the disease is the presence of antimitochondrial antibodies (AMAs), which are found in 95% of patients with PBC. AMAs have been shown to be directed against the 2-oxo-acid dehydrogenase complexes located on the inner membrane of the mitochondria. However, AMA titers do not correlate with the disease severity of progression, and the role of AMAs in the pathogenesis of PBC has not been shown. The disease is frequently associated with other autoimmune diseases, including Sjögren's syndrome, scleroderma and thyroid disorders. Most therapeutic efforts have been directed at altering the immune response. Ursodeoxycholic acid (UDCA) appears to be effective therapy in preventing or delaying the need for liver transplantation and improving survival. However, a number of patients receiving UDCA still develop progressive disease and go on to transplantation, which is an effective therapy at the end stage of the disease. Various prognostic models have been proposed to estimate the survival probability and assist in the determination of the optimum timing of liver transplantation.