Quiz Ref ID Systemic sclerosis is a heterogeneous autoimmune connective tissue disease characterized by vasculopathy, autoantibody formation, low-grade inflammation, and fibrosis in skin and internal organs, with varying geographical prevalence (50-300 per million persons per year) and incidence (2.3-22.8 per million persons per year).^1,2 Previous studies have shown that systemic sclerosis is amenable to treatment with autologous hematopoietic stem cell transplantation (HSCT).^3-9 Improvement of skin involvement and functional ability was consistently observed, although some studies showed that HSCT can also ameliorate vasculopathy, improve skin and lung involvement, and correct immune abnormalities.^10-13 The benefits of HSCT must be weighed against the risk of serious toxicities due to organ involvement in systemic sclerosis.¹⁴ It is still unclear whether HSCT prolongs survival in systemic sclerosis. We therefore conducted a randomized clinical trial called ASTIS (Autologous Stem Cell Transplantation International Scleroderma) to compare safety and efficacy of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide.

Objective To investigate the in vitro ability of antiphospholipid antibodies (aPL) to bind human trophoblast cells and to affect gonadotropin secretion and invasiveness. Methods Antiphospholipid antibody IgG from women with recurrent miscarriages, β₂‐glycoprotein I (β₂GPI)–independent IgG aPL human monoclonal antibody (mAb)(519), and IgM anti‐β₂GPI human mAb (TM1G2) were investigated for their binding to trophoblasts cultured for various amounts of time, their ability to affect invasiveness of Matrigel‐coated filters, and their release of human chorionic gonadotropin (hCG). Results Polyclonal IgG aPL, as well as mAb 519 and TM1G2, bound to trophoblasts, the highest binding being found when cells displayed the greatest amount of syncytium formation. TM1G2 binding was found to be β₂GPI dependent. Both polyclonal and monoclonal aPL, but not the controls, significantly reduced hCG release and Matrigel invasiveness. Conclusion These findings suggest that aPL recognition of both anionic PL and adhered β₂GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome.

Objectives: To measure the prevalence of, and factors associated with, left ventricular (LV) dysfunction in systemic sclerosis (SSc). Methods: The EUSTAR database was first searched. A case-control study of a patient subset was then performed to further identify independent factors associated with LV dysfunction by simple and multiple regression. Results: Of 7073 patients, 383 (5.4%) had an LV ejection fraction (EF) of <55%. By multiple regression analysis, age, sex, diffuse cutaneous disease, disease duration, digital ulcerations, renal and muscle involvement, disease activity score, pulmonary fibrosis and pulmonary arterial hypertension were associated with LV dysfunction. In the second phase, 129 patients with SSc with LVEF <55% were compared with 256 patients with SSc with normal LVEF. Male sex (OR 3.48; 95% CI 1.74 to 6.98), age (OR 1.03; 95% CI 1.01 to 1.06), digital ulcerations (OR 1.91; 95% CI 1.05 to 3.50), myositis (OR 2.88; 95% CI 1.15 to 7.19) and use of calcium channel blockers (OR 0.41; 95% CI 0.22 to 0.74) were independent factors associated with LV dysfunction. Conclusion: The prevalence of LV dysfunction in SSc is 5.4%. Age, male gender, digital ulcerations, myositis and lung involvement are independently associated with an increased prevalence of LV dysfunction. Conversely, the use of calcium channel blockers may be protective.

Objective. To investigate the ability of human anti‐β₂‐glycoprotein I (anti‐β₂GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions.Methods. Six human affinity‐purified polyclonal anti‐β₂GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphos‐pholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent β₂GPI and 2) modulate endothelial adhesion molecule expression and interleukin‐6 (IL‐6) and 6‐keto‐prostaglandin F_1α (6‐keto‐PGF_1α) secretion.Results. The affinity‐purified IgG and the MAb with anti‐β₂GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum‐free medium and was restored in a dose‐dependent manner by exogenous human β₂GPI. After EC binding, both polyclonal and monoclonal antibodies up‐regulated adhesion molecule expression. Anti‐β₂GPI MAb also significantly increased IL‐6 and 6‐keto‐PGF_1α secretion.Conclusion. These findings support the hypothesis that anti‐β₂GPI antibodies bind and activate EC through the adherent cofactor β₂GPI, likely leading to a procoagulant state.

Antisynthetase syndrome (ASSD) is a rare clinical condition that is characterized by the occurrence of a classic clinical triad, encompassing myositis, arthritis, and interstitial lung disease (ILD), along with specific autoantibodies that are addressed to different aminoacyl tRNA synthetases (ARS). Until now, it has been unknown whether the presence of a different ARS might affect the clinical presentation, evolution, and outcome of ASSD. In this study, we retrospectively recorded the time of onset, characteristics, clustering of triad findings, and survival of 828 ASSD patients (593 anti-Jo1, 95 anti-PL7, 84 anti-PL12, 38 anti-EJ, and 18 anti-OJ), referring to AENEAS (American and European NEtwork of Antisynthetase Syndrome) collaborative group’s cohort. Comparisons were performed first between all ARS cases and then, in the case of significance, while using anti-Jo1 positive patients as the reference group. The characteristics of triad findings were similar and the onset mainly began with a single triad finding in all groups despite some differences in overall prevalence. The “ex-novo” occurrence of triad findings was only reduced in the anti-PL12-positive cohort, however, it occurred in a clinically relevant percentage of patients (30%). Moreover, survival was not influenced by the underlying anti-aminoacyl tRNA synthetase antibodies’ positivity, which confirmed that antisynthetase syndrome is a heterogeneous condition and that antibody specificity only partially influences the clinical presentation and evolution of this condition.

Objective: To develop valid instruments for the assessment of disease‐related damage and disease activity in Sjögren's syndrome (SS).Methods: Data on 206 patients with primary SS were collected in 12 Italian centers. Each patient was scored by 1 investigator, on the basis of a global assessment of the degree of disease damage and disease activity. Patients judged to have active disease at the time of enrollment underwent a second evaluation after 3 months. Univariate and multivariate analyses were performed to select the clinical and serologic variables that were the best predictors of damage and of disease activity, and these variables were used to construct the Sjögren's Syndrome Disease Damage Index (SSDDI) and the Sjögren's Syndrome Disease Activity Index (SSDAI). The weight of each variable in the index was determined by the β coefficients in multivariate regression models. Scores obtained using the SSDDI and the SSDAI were compared with scores initially given by the investigators. Finally, a receiver operating characteristic (ROC) curve was used to determine the cutoff value in the SSDAI with the highest level of accuracy in identifying patients with a significant level of disease activity.Results: A multivariate model with 9 variables was the best predictor of investigator scores of damage. The scores obtained using the SSDDI were closely correlated with investigator ratings (R = 0.760, P < 0.0001). A model composed of 11 variables was the best predictor of investigator scores of disease activity. The scores obtained using the SSDAI were strongly correlated with the investigator ratings both at the time of enrollment and 3 months after enrollment (R = 0.872, P < 0.0001, and R = 0.817, P < 0.0001, respectively). The differences between scores given by investigators at study enrollment and after 3 months, a measure of variation of disease activity over time, were also closely correlated with the differences calculated using the SSDAI (R = 0.683, P < 0.0001). The ROC curve analysis showed that patients with the highest level of disease activity could be identified on the basis of an SSDAI score of ≥5.Conclusion: Our findings indicate that the SSDDI is an adequate instrument to objectively measure damage in patients with SS, and that the SSDAI is a valid tool to measure disease activity when used either as a single‐state index or as a transition index.