Objective: To assess fetal and maternal outcomes in women with systemic sclerosis (SSc).Methods: Prospectively collected data on 99 women with SSc from 25 Italian centers were analyzed retrospectively. Women with SSc were observed during 109 pregnancies (from 2000 to 2011), and outcomes were compared to those in the general obstetric population (total of 3,939 deliveries). The maternal age at conception was a mean ± SD 31.8 ± 5.3 years, and the median disease duration at conception was 60 months (range 2–193 months).Results: SSc patients, compared to the general obstetric population, had a significantly increased frequency of preterm deliveries (25% versus 12%) and severe preterm deliveries (<34 weeks of gestation) (10% versus 5%), intrauterine growth restriction (6% versus 1%), and babies with very‐low birth weight (5% versus 1%). Results of multivariable analysis showed that corticosteroid use was associated with preterm deliveries (odds ratio [OR] 3.63, 95% confidence interval [95% CI] 1.12–11.78), whereas the use of folic acid (OR 0.30, 95% CI 0.10–0.91) and presence of anti–Scl‐70 antibodies (OR 0.26, 95% CI 0.08–0.85) were protective. The disease remained stable in most SSc patients, but there were 4 cases of progression of disease within 1 year from delivery, all in anti–Scl‐70 antibody–positive women, 3 of whom had a disease duration of <3 years.Conclusion: Women with SSc can have successful pregnancies, but they have a higher‐than‐normal risk of preterm delivery, intrauterine growth restriction, and babies with very‐low birth weight. Progression of the disease during or after pregnancy is rare, but possible. High‐risk multidisciplinary management should be standard for these patients, and pregnancy should be avoided in women with severe organ damage and postponed in women with SSc of recent onset, particularly if the patient is positive for anti–Scl‐70 antibodies.

Objectives The marked cardiovascular risk in autoimmune diseases is only partly explained. The capacity of high-density lipoproteins (HDL) to promote cell cholesterol efflux is a property with a well-known anti-atherogenic significance, but is also involved in functional modulation of endothelial and immune cells. The aim of this work was to evaluate HDL functionality with respect to cell cholesterol efflux in rheumatoid arthritis (RA) and systemic lupus erythemathosus (SLE) patients. Methods We evaluated serum cholesterol efflux capacity (CEC) of apoB-depleted serum, which mainly reflects HDL activity, from 30 RA and 30 SLE patients, and from 30 healthy controls by radioisotopic ex-vivo systems discriminating between the specific pathways of cholesterol efflux. Results RA patients presented impairment of ATP-binding cassette G1-mediated CEC that correlated with disease activity. SLE patients showed a more complex pattern of modifications unrelated to disease activity, with marked reduction of ATP-binding cassette G1-mediated CEC and impairment of ATP-binding cassette A1-mediated CEC. The relationship between specific pathways of CEC values and serum total HDL differed between groups and there was no relationship with autoantibody profile or current therapy. Conclusions 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.

Objective: It has been suggested that only antibodies against domain 1 (D1) of β₂‐glycoprotein I (β₂GPI) are pathogenic and diagnostic. The role of antibodies against other β₂GPI domains is still debated. This study was undertaken to evaluate the clinical relevance of domain specificity profiling of anti‐β₂GPI 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‐β₂GPI 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‐β₂GPI D1 and D4/5 IgG were tested on research enzyme‐linked immunosorbent assays containing recombinant β₂GPI 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 = 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‐β₂GPI 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.