Effect of Additional Treatments Combined with Conventional Therapies in Pregnant Patients with High-Risk Antiphospholipid Syndrome: A Multicentre Study.

The effect of additional treatments combined with conventional therapy on pregnancy outcomes was examined in high-risk primary antiphospholipid syndrome (PAPS) patients to identify the most effective treatment strategy. The study's inclusion criteria were (1) positivity to lupus anticoagulant alone or associated with anticardiolipin and/or anti-ß2 glycoprotein I antibodies; (2) a history of severe maternal-foetal complications (Group I) or a history of one or more pregnancies refractory to conventional therapy leading to unexplained foetal deaths not associated with severe maternal-foetal complications (Group II). Two different additional treatments were considered: oral-low-dose steroids (10-20 mg prednisone daily) and/or 200 to 400 mg daily doses of hydroxychloroquine and parenteral-intravenous immunoglobulins at 2 g/kg per month and/or plasma exchange. The study's primary outcomes were live birth rates and pregnancy complications. A total of 194 pregnant PAPS patients attending 20 tertiary centres were retrospectively enrolled. Hydroxychloroquine was found to be linked to a significantly higher live birth rate with respect to the other oral treatments in the Group II patients. The high (400 mg) versus low (200 mg) doses of hydroxychloroquine (p = 0.036) and its administration before versus during pregnancy (p = 0.021) were associated with a significantly higher live birth rate. Hydroxychloroquine therapy appeared particularly efficacious in the PAPS patients without previous thrombosis. Parenteral treatments were associated with a significantly higher live birth rate with respect to the oral ones (p = 0.037), particularly in the Group I patients. In conclusion, some additional treatments were found to be safe and efficacious in high-risk PAPS pregnant women.

Antiphospholipid Antibodies and Infertility: A Gene Expression Study in Decidual Stromal Cells.

BACKGROUND: Antiphospholipid antibodies (aPL) have been advocated as potential mediators of unexplained female infertility, but no evidence has yet been raised to support such an association. OBJECTIVES: To test the hypothesis that aPL might interfere with uterine decidualization, a gene expression study was performed on decidual stromal cells treated with different aPL preparations. METHODS: Decidual stromal cells were isolated from first-trimester deciduas obtained from two women undergoing elective abortion, and treated with: (i) a ß2GPI-dependent aPL monoclonal antibody (IS3); (ii) IS3 plus TIFI, a synthetic peptide mimicking PL-binding region of ß2GPI; and (iii) IgG from healthy subjects (NHS). Gene expression data were acquired using human HT-12 v3 beadchip arrays (Illumina). Differential expression analysis was performed by fitting a gene-wise linear model using the treatment group and decidual source as covariates. RESULTS: In the comparison of IS3 versus IgG NHS-treated decidual cells, gene ontology (GO) enrichment was expressed in terms relating to well-characterized aPL-mediated cellular effects: "inflammatory response," "immune response," "response to stress," "oxydoreductase activity," "metalloendopeptidase activity," and "cytokine/chemokine activity." As expected, almost all genes were up-regulated by IS3 treatment. The same GO categories appeared to be differentially expressed when IS3 treatment was compared to IS3 + TIFI, but with most genes being down-regulated. CONCLUSIONS: Given the inflammatory response evinced on gene expression analysis of decidual stromal cells treated with a ß2GPI -dependent aPL monoclonal antibody, it is feasible that aPL might interfere with uterine decidualization, affecting the early stages of implantation and ultimately resulting in female infertility.

Detection of anti-IFI16 antibodies by ELISA: clinical and serological associations in systemic sclerosis.

OBJECTIVES: To validate the clinical significance of anti-IFI16 autoantibodies in SSc and assess their associations with serological markers of SSc. METHODS: A semi-quantitative ELISA was used to detect anti-IFI16 autoantibodies in the sera of 344 SSc patients from seven Italian hospitals and 144 healthy controls. SSc-associated autoantibodies [anti-RNA polymerase III (anti-RNAP III) antibodies, anti-centromere, anti-topo I] and IF patterns were evaluated using commercial assays. Statistical analyses were performed to test clinical and serological associations. RESULTS: The results of this study confirm a significant prevalence (29%) of anti-IFI16 antibodies in the SSc population (n = 344). Anti-IFI16 antibodies were also detected in 30% of the SSc patients who tested negative for both ACAs and anti-topo I (anti-Scl70) antibodies. In this subgroup of patients, anti-IFI16 antibodies were significantly associated with the limited cutaneous form of SSc with a sensitivity of 40% and a specificity of 81%. Moreover, analysis of the distribution of anti-RNAP III antibodies vs anti-IFI16 in the same SSc population showed that they were mutually exclusive. IIF revealed no association between anti-IFI16 and fluoroscopic patterns, due to a lack of IFI16 autoantigen in HEp-2 cells. Anti-IFI16 antibody levels were also significantly associated with heart involvement. CONCLUSIONS: Anti-IFI16 autoantibodies are frequently detected in SSc, displaying clinical and laboratory associations, and being particularly useful for diagnosis and disease classification in patients who are negative for other SSc serological markers.

Inflammation and accelerated atherosclerosis: basic mechanisms.

This article summarizes knowledge of the pathogenic mechanisms in autoimmune rheumatic diseases as risk factors for accelerated atherosclerosis. The studies described support a role for immunologic-inflammatory mechanisms in the pathogenesis of atherosclerosis. This immunologic-inflammatory state is evident in many autoimmune diseases, but also in the general population lacking an overt autoimmune disease. The ability to immunomodulate atherosclerosis (currently only experimental) should lead to future research into the mechanisms and treatment of atherosclerosis, the leading cause of death in the Western world.