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A premature atherosclerosis has been presumed in patients with antiphospholipid syndrome. The potential role of antiphospholipid antibodies in the development of atheroma is rather controversial. In this study, we tested the hypothesis that antiphospholipid antibodies could induce atherosclerosis via vascular functional changes. CD1 mice received one single injection of antiphospholipid monoclonal antibodies derived from male (BXSB × NZW) F1 mice with a lupus-like disease associated with an antiphospholipid syndrome and coronary artery disease. One week later, first-order mesenteric arteries (diameter 220-260 μm) were isolated and mounted on a small-vessel myograph for the measurement of the relaxation responses to acetyicholine or the NO donor nitroprusside after precontraction by phenylephrine. Five out of eight antiphospholipid monoclonal antibodies reduced the response to acetylcholine compared with control mice, and this effect was especially marked with one of them. No change in the response to nitroprusside was observed. The impairment was maintained after 3 weeks of treatment and appeared related to a moderate decrease in NO-mediated responses and a marked decrease in prostanoid-mediated relaxations. These vascular functional changes could be prevented by chronic treatment with statins or aspirin. These data could constitute additional elements supporting a direct pathogenic role of antiphospholipid antibodies. We suggest that a sub-population of these autoantibodies could be responsible for the endothelial dysfunction observed in antiphospholipid syndrome. [ABSTRACT FROM AUTHOR]

The objective of this study was to determine in systemic lupus erythematosus (SLE) the prevalence and clinical significance of anticalpastatin antibodies (ACAST), an autoantibody population previously detected in sera from patients with various connective tissue diseases. Eighty-four patients with SLE (mean age: 30 years at diagnosis, females 77) that fulfilled ACR criteria were included in the study retrospectively. Several clinical and biological data were collected. ACAST were detected by a solidphase enzyme linked immunosorbent assay (ELISA) using as antigen a synthetic peptide corresponding to the 27 C-terminal amino acids of calpastatin (CAST-C27). The prevalence of ACAST-C27 was 13% (11/84) in SLE patients. No correlation was found between the presence of ACAST-C27 and clinical manifestations such as thrombosis and vasculitis. Furthermore, no correlation was observed with the presence of antiphospholipid antibodies (APL). However, we found a statistically significant association between the presence of ACAST-C27 and that of secondary Sjögren syndrome (P =; 0.01). The conclusion is ACAST-C27 are not associated with thrombosis in SLE patients. The association observed between ACAST-C27 and secondary Sjögren syndrome suggests that ACAST-C27 might be useful in discriminating a clinical subgroup of SLE patients. [ABSTRACT FROM AUTHOR]

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(NZB × NZW)F1 (B/W) mice spontaneously produce anti-deoxyribonucleic (DNA) acid antibodies. PME77 anti-DNA monoclonal antibody (MoAb) is a syngeneic antibody bearing idiotype present in most B/W sera, in the present investigation the effect of immunization of B/W mice with the PME77 MoAb on the production of FME77 idiotypes and anti-DNA antibodies in B/W mouse sera was investigated. PME77 MoAb immunization regimen induced the production of autoanti-idiotypic antibodies and abrogated the expression of PM E77 idiotype in B/W treated mice. In contrast, untreated mice and control B/W mice, receiving NZB polyclonal IgG2b which lacked detectable DNA binding capacity, expressed PME77 idiotopes. These results demonstrate that the expression of idiotype borne by autoantibodies may be modified through the induction of autoanti-idiotypic antibodies. [ABSTRACT FROM AUTHOR]

Anti-native DNA antibodies have been evaluated in forty-six lupus patients' sera for antigen-binding capacity, affinity and precipitating activity, Diffuse proliferative glomerulonephritis was significantly correlated with the presence of high serum level of free anti-native DNA antibodies. Weak affinities were more often found in patients with than without glomerular changes but several patients had high-affinity anti-DNA antibodies and severe glomerulonephritis. No correlation was found between anti-DNA antibody-precipitating activity and renal lesions. [ABSTRACT FROM AUTHOR]

Since lymphoid organs constitute the site of active and progressive HIV disease, analysis of their lymphocytes may provide more accurate information on T cell abnormalities than that obtained from studying peripheral blood lymphocytes. The objective of this study was to compare the expressions of activation markers and T cell receptor (TCR) Vβ gene products by CD4+ and CD8+ T cells in lymph nodes (LN) and peripheral blood (PB) from healthy individuals and asymptomatic HIV-infected patients to determine whether anomalies that could be identified at the HIV replication site could support the hypothesis of T cell activation by HIV-encoded antigens or superantigens. CD4+ and CD8+ T cells in paired LN and PB obtained from six healthy controls and five asymptomatic HIV-infected individuals were analysed by flow cytometry, using anti- CD38, anti-HLA-DR and 13 anti-Vβ MoAbs that cover, approximately. 45% of the T cell repertoire. Analysis of T cell activation marker expression indicated that the percentages of CD4+ and CD8+ T cells bearing CD38 or CD38 and HLA-DR molecules were higher in patients than in controls and, in patients, higher in LN than in PB. Comparison between the V&beta repertoires of CD4+ and CD8+ T cells in LN and PB showed that, in each healthy individual, a limited number of Vβ families expressed by CD4+ or CD8+ T cells had different repartition in LN and PB, whereas in each HIV patient, more Vβ families exhibited different distributions and these differences recurred among certain Vβ segments, such as Vβ5.3 and Vβ21 in the CD4+ T cell population and Vβ5.2/5.3, Vβ12 and Vβ21 in the CD8+ T cell population. Taken together, these data argue for a skewed TCR repertoire in HIV infection and sustained activation of T cells by HIV-encoded antigens at the site of HIV replication, and further demonstrate that a high proportion of CD4+ T cells are in an activation state that may, indirectly, participate in their functional abnormalities. [ABSTRACT FROM AUTHOR]

We have studied complement activation both in plasma samples and in lesional skin from patients with leukoeytoclastic cutaneous vasculitis (LCV). Enzyme immunoassay (EIA) quantification of the complement activation markers, C3d,g and the terminal complement complex (TCC) in plasma, showed that their levels were significantly increased in 66% and 55% of the patients. Respectively (n = 29) compared with healthy controls, whereas the standard measurements of C3, factor B, Clq, C4 and C2 were generally within normal range. Elevations of C3d,g and TCC levels in plasma were significantly correlated. Importantly, a significant correlation was found between the severity of the vaseulitis and both C3d,g and TCC plasma levels. Immunofluoreseence studies of skin biopsy specimens demonstrated simultaneous presence of perivascular dermal deposits of C3d,g and TCC in lesional skin from 96% and 80% respectively of the patients (n = 25). There was a significant correlation between the intensity of the deposits of both markers. Clusterin, a TCC inhibitory protein, was always found at the same sites of perivascular TCC deposits. Immunofluorescence studies at the epidermal basement membrane zone (BMZ) revealed in each case deposits of C3d,g which were accompanied by TCC deposits in 52% of the biopsy specimens. These data demonstrate that there is a local and systemic activation of the whole complement cascade in human LCV. The presence of both C3d,g and clusterin-associated TCC perivascular deposits suggests an intervention of a regulatory mechanism of local complement activation in LCV. Finally, measurement of plasma C3d,g and TCC appears to be a sensitive indicator of systemic complement activation and disease severity in LCV. [ABSTRACT FROM AUTHOR]

IgG and IgM anticardiolipin antibodies (aCA) were studied prospectively in 20 consecutive patients (12 females, eight males, mean age 74.6 ± 14 yr, range 62–86 yr) with giant cell temporal arteritis before and during corticosteroid therapy (days 7, 30, 90 and 180). IgG-aCA were present in 10 out of 20 cases and in nine out of 12 with positive temporal artery biopsy but were not found in 20 paired control subjects. During steroid therapy aCA levels returned to within the normal range in 60% of patients with positive aCA at day 7 and in 80% at day 30. In two cases aCA persisted during the 6-month follow-up despite clinical and biological success. No association was found between aCA and thrombotic events. [ABSTRACT FROM PUBLISHER]

We report a case of herpetiform pemphigus induced by thiopronine. Direct immunoelectron microscopy performed on peribullous skin showed IgG deposits predominantly located in the extracellular portion of desmosomes. By immunoblot analysis using bovine tongue extracts as the antigen, the patient's serum recognized a 160-kDa polypeptide which comigrated with desmoglein I. This study underlines the contribution of immunoblot analysis to the diagnosis of atypical cases of pemphigus, and confirms that herpetiform pemphigus may be a clinical variant of pemphigus foliaceus. [ABSTRACT FROM AUTHOR]