Objective. Antiphospholipid Syndrome Alliance For Clinical Trials and International Networking (APS ACTION)Results. Based on the analysis of 120 full-text papers, the overall aPL frequency was estimated as 6% for PM, 13.5% for ST, 11% for MI, and 9.5% for DVT. Limitations of the literature were that 60% of the papers were published before 2000, all 3 criteria aPL tests were performed in only 11% of the papers, 36% of papers used a low-titer aCL cutoff, anti-␤ 2 GPI cutoff was quite heterogeneous, aPL confirmation was performed in only one-fifth of papers, and the study design was retrospective in nearly half of the papers. Conclusion. It is difficult to determine the frequency of a "clinically significant aPL profile" in patients with aPL-related clinical outcomes due to the lack of robust data. Our best estimates of the incidence of aPL-associated events should be confirmed with appropriately designed population studies.

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CEC is impaired in RA and SLE, with a specific mechanism pattern in each disease not depending on serum HDL levels. These findings provide a new mechanism for the increased atherosclerotic risk in RA and SLE patients.

IntroductionWe assessed the profile and frequency of malignancy subtypes in a large single-centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc patients with different antibody reactivities and explored the temporal association of cancer with the duration between SSc onset and cancer diagnosis.MethodsWe conducted a retrospective study of a well-characterised cohort of SSc patients attending a large tertiary referral centre, with clinical data collected from our clinical database and by review of patient records. We evaluated development of all cancers in this cohort, and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details, including antibody reactivities, were explored to find associations relevant to the risk for development of cancer in SSc patients.ResultsAmong 2,177 patients with SSc, 7.1% had a history of cancer, 26% were positive for anticentromere antibodies (ACAs), 18.2% were positive for anti-Scl-70 antibodies and 26.6% were positive for anti-RNA polymerase III (anti-RNAP) antibody. The major malignancy cancer subtypes were breast (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased compared with those with anti-Scl-70 antibodies (6.3%) and ACAs (6.8%) (P < 0.0001 and P < 0.001, respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than those with other autoantibody specificities (ACA = 23.5%, P < 0.008; and anti-Scl-70 antibodies = 13.6%, P < 0.002, respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP, and SSc patients with anti-RNAP had a twofold increased hazard ratio for cancers compared to patients with ACAs (P < 0.0001).ConclusionsOur study independently confirms, in what is to the best of our knowledge the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of cautious suspicion should be maintained in these cases, and investigations for underlying malignancy should be considered when clinically appropriate.

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Objective. It has been suggested that only antibodies against domain 1 (D1) of b 2 -glycoprotein I (b 2 GPI) are pathogenic and diagnostic. The role of antibodies against other b 2 GPI domains is still debated. This study was undertaken to evaluate the clinical relevance of domain specificity profiling of anti-b 2 GPI IgG antibodies in antiphospholipid syndrome (APS) patients and in control groups of patients with systemic autoimmune rheumatic diseases and in asymptomatic antiphospholipid antibody (aPL) carriers.Methods. We evaluated 159 subjects with persistently positive, medium or high-titer anti-b 2 GPI IgG, including 56 patients with thrombotic (obstetric or nonobstetric) primary APS, 31 women with obstetric primary APS, 42 aPL-positive patients with systemic autoimmune rheumatic diseases, and 30 asymptomatic aPL carriers. One hundred healthy donors were included. Anti-b 2 GPI D1 and D4/5 IgG were tested on research enzyme-linked immunosorbent assays containing recombinant b 2 GPI domains.Results. As compared to other groups, aPL carriers displayed higher frequency/titer of anti-D4/5 IgG. Unlike anti-D4/5, anti-D1 IgG antibodies were more frequent and at higher titer in triple than in single or double aPL-positive subjects. An anti-D1 to anti-D4/5 ratio of ‡1.5 was predictive of systemic autoimmunity (odds ratio 3.25 [95% confidence interval 1.45-7.49], P 5 0.005). Neither anti-D1 nor anti-D4/5 antibodies were associated with APS clinical criteria.Conclusion. Anti-D1 IgG is the preferential specificity not only in vascular and obstetric primary APS, but also in patients with systemic autoimmune rheumatic disease with no clinical features of APS. Conversely, aPL carriers do not have a polarized profile toward D1. Combined testing for anti-b 2 GPI IgG with different domain specificity allows a more accurate aPL profiling, with polarization toward anti-D1 IgG as a possible fingerprint of systemic autoimmunity.

The clinical spectrum of the anti-phospholipid syndrome (APS) is not limited to vascular thrombosis or miscarriages but includes additional manifestations that cannot be explained solely by a thrombophilic state. Anti-cardiolipin, anti-beta2 glycoprotein I (anti-β2GPI) and lupus anticoagulant (LA) assays are not only the formal diagnostic and classification laboratory tools but also parameters to stratify the risk to develop the clinical manifestations of the syndrome. In particular, anti-β2GPI antibodies reacting with an immunodominant epitope on domain I of the molecule were reported as the prevalent specificity in APS patients, correlating with a more aggressive clinical picture. Several laboratory assays to improve the diagnostic and predictive power of the standard tests have been proposed. Plates coated with the phosphatidylserine-prothrombin complex for detecting antibodies represent a promising laboratory tool correlating with LA and with clinical manifestations. Anti-phospholipid antibodies can be found in patients with full-blown APS, in those with thrombotic events or obstetric complications only or in asymptomatic carriers. An inflammatory second hit is required to increase the presence of β2GPI in vascular tissues, eventually triggering thrombosis. Post-transcriptional modifications of circulating β2GPI, different epitope specificities or diverse anti-β2GPI antibody-induced cell signaling have all been suggested to affect the clinical manifestations and/or to modulate their occurrence.

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