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Y Shoenfeld

Publications and source records attributed to Y Shoenfeld.

946 records · Page 53Linked to original sources

Levels of lupus autoantibodies in pregnant SLE patients: correlations with disease activity and pregnancy outcome.

OBJECTIVE: To follow the levels of lupus autoantibodies throughout pregnancy in a large cohort of pregnant SLE patients, and to examine whether they correlate with disease activity and pregnancy outcome. METHODS: 54 pregnancies in 46 SLE patients, and 70 control pregnant women were followed in the study. All patients were receiving steroid treatment. Titers of antibodies to ssDNA, dsDNA, histones, cardiolipin (CL) and phosphatidylserine (PS) were determined at the first, second, and third trimester and post-partum by ELISA. RESULTS: Overall the average levels of autoantibodies in all the patients were within the normal range, except for the average levels of anti-dsDNA antibodies which were elevated during the second trimester. Eight women (14.5%) had active disease during pregnancy, and there was a significant correlation between the levels of anti-dsDNA and the risk of disease activity (p = 0.0225). There were 7 fetal losses. There was a tendency for correlation between elevated anti-dsDNA levels, and anti-CL levels and the risk of fetal loss; however, this did not reach statistical significance (p = 0.0685, and 0.0881, respectively). There was a significant correlation between the levels of anti-dsDNA antibodies and the risk of preterm delivery (p = 0.0331). CONCLUSIONS: Pregnancy in SLE patients is associated with significant complications to both the mother and the fetus. Anti-dsDNA levels seem to correlate with the risk of disease exacerbation, and prematurity. Elevated levels of anti-dsDNA and anti-CL may suggest an increased risk of fetal loss.

Adult↗

Superantigens and experimental SLE induced by idiotypic dysregulation.

OBJECTIVE: The effects of the superantigens (SAgs) Staphylococcal Enterotoxin B (SEB), Toxic Shock Syndrome Toxin-1 (TSST-1) and Mycoplasma Arthritidis Mitogen (MAM) were examined on the induction and on the course of experimental SLE-like disease. METHODS: Immunization of BALB/c mice with human anti-DNA mAb (MIV-7) carrying the pathogenic idiotype 16/6 emulsified in complete Freund's adjuvant (CFA), followed by a boost of MIV-7/PBS 3 weeks later, generated an experimental SLE via an idiotypic dysregulation. RESULTS: After immunization with MIV-7/SAg, replacing the MIV-7 boost by SAg, and then injecting SAg 7 weeks after the regular induction of the SLE-like disease, the mice failed to produce anti-hIgM and dsDNA Ab up to 6 months after the induction. The mice immunized with MIV-7/CFA and boosted with the SAg had high titers of anti-hIgM but no detectable anti-dsDNA Ab. In both experimental groups low titers of anti-CL Abs developed in 25/40 (62%) and 30/38 (79%) of the mice respectively, including the control mice immunized with non-pathogenic human IgM/SAg or PBS/SAg. The mice immunized according to the "classical" protocol showed increased titers of anti-dsDNA Ab (22%) and anti-CL Ab (28%) during 10 weeks of observation. In contrast SEB, TSST-1 and MAM induced a 29%, 1% and 17% reduction in the anti-DNA titers and a 32%, 15% and 12% reduction in the anti-CL titers, respectively. CONCLUSIONS: These data suggest that the SAg tested here cannot replace the effect of CFA in the induction of the primary humoral response. The SAgs TSST-1, SEB and MAM did not induce the SLE-like disease following idiotypic modulation. Moreover, they may have had a suppressive effect on the idiotypic network in our model. The appearance of anti-CL Abs in almost all the experimental groups including the naive mice supports the possibility that microbial SAgs can induce the production of autoantibodies by different mechanisms. The SAgs TSST-1, SEB and MAM reduced autoantibody production in the serologically established idiotypic-induced experimental SLE-like murine model. This beneficial effect may indicate new directions for research on the management of SLE.

Animals↗

Anti-neutrophil cytoplasmic antibodies in patients with chromomycosis.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are a family of antibodies that react to proteins within neutrophil granules and monocyte lysosomes, and occur prominently in sera from patients with systemic necrotizing vasculitis. The cytoplasmic staining pattern (c-ANCA) is very sensitive and specific for Wegener's granulomatosis (WG), and most commonly results from reactivity with proteinase 3 (PR3). The features of tissue damage in the fungal infection chromomycosis, in particular polymorphonuclear neutrophil (PMN) infiltration and granuloma formation, bear a resemblance to that seen in WG. METHODS: We tested sera from 25 patients with clinical and histologic diagnosis of chromomycosis for the presence of ANCA by indirect immunofluorescence. These same sera were analyzed for reactivity to neutrophil primary granule extracts and PR3 by ELISA. RESULTS: Five of the 25 patients (20%) had detectable c-ANCA, without central accentuation, at serum dilutions of at least 1:40. Three of these 5 ANCA-positive patients reacted with neutrophil primary granule extracts by ELISA; however, none of them reacted with PR3. CONCLUSIONS: These results demonstrate that fungal infection should be included among the conditions, unrelated to necrotizing vasculitis, that can trigger autoreactivity against myeloid lysosomal antigens.

Adult↗

Association of 16/6 and SA1 anti-DNA idiotypes with anticardiolipin antibodies and clinical manifestations in a large cohort of SLE patients. European Concerted Action on the Immunogenetics of SLE.

OBJECTIVE: The SA1 and 16/6 idiotypes can be found in some patients with systemic lupus erythematosus (SLE) or anti-phospholipid syndrome (APS). The aim of this study was to ascertain the prevalence of these idiotypes in a large cohort of SLE patients, and to determine whether their presence is correlated with the anticardiolipin (aCL) and anti-dsDNA antibodies or with the clinical manifestations of SLE. METHODS: 492 SLE patients were evaluated for clinical manifestations of SLE and were assigned a disease severity score. ds-DNA autoantibodies, aCL autoantibodies of the IgM, IgG and IgA isotypes, and SA1 and 16/6 idiotypes were also determined in these patients. RESULTS: The prevalence of the SA1 and 16/6 idiotypes in the 492 SLE patients was found to be 11% and 5.1%, respectively, and these idiotypes were significantly more prevalent in the patients who had aCL antibodies of either the IgG, IgM or IgA isotypes. Moreover, while the 16/6 idiotype was not associated with the clinical manifestation of either SLE or APS, the SA1 idiotype was found significantly more frequently in patients who had vascular events Raynaud's phenomenon or hemolytic anemia (p = 0.016, 0.01, 0.01, respectively). CONCLUSION: SLE patients with the SA1 idiotype may run a higher risk of developing vascular events, Raynaud's phenomenon or hemolytic anemia. These clinical manifestations can be attributed to both SLE and secondary APS when aCL autoantibodies are also found. These results indicate that the possible pathogenicity of certain idiotypes in SLE cannot be excluded.

Adolescent↗