Objective: To define the antiphospholipid score (aPL‐S) by testing multiple antiphospholipid antibodies (aPL) and to evaluate its efficacy for the diagnosis of antiphospholipid syndrome (APS) and predictive value for thrombosis.Methods: This study comprised 2 independent sets of patients with autoimmune diseases. In the first set of patients (n = 233), the aPL profiles were analyzed. Five clotting assays for testing lupus anticoagulant and 6 enzyme‐linked immunosorbent assays (IgG/IgM anticardiolipin antibodies, IgG/IgM anti–β₂‐glycoprotein I, and IgG/IgM phosphatidylserine‐dependent antiprothrombin antibodies) were included. The association of the aPL‐S with a history of thrombosis/pregnancy morbidity was assessed. In the second set of patients (n = 411), the predictive value of the aPL‐S for thrombosis was evaluated retrospectively. Two hundred ninety‐six of these patients were followed up for >2 years. The relationship between the aPL‐S and the risk of developing thrombosis was analyzed.Results: In the first set of patients, the aPL‐S was higher in those with thrombosis/pregnancy morbidity than in those without manifestations of APS (P < 0.00001). For the aPL‐S, the area under the receiver operating characteristic curve value was 0.752. In the second set of patients, new thromboses developed in 32 patients. The odds ratio (OR) for thrombosis in patients with an aPL‐S of ≥30 was 5.27 (95% confidence interval [95% CI] 2.32–11.95, P < 0.0001). By multivariate analysis, an aPL‐S of ≥30 appeared to be an independent risk factor for thrombosis (hazard ratio 3.144 [95% CI 1.383–7.150], P = 0.006).Conclusion: The aPL‐S is a useful quantitative index for diagnosing APS and may be a predictive marker for thrombosis in autoimmune diseases.

Dysregulation of Th17 and Treg cells contributes to the pathophysiology of many autoimmune diseases. Herein, we show that itaconate, an immunomodulatory metabolite, inhibits Th17 cell differentiation and promotes Treg cell differentiation by orchestrating metabolic and epigenetic reprogramming. Mechanistically, itaconate suppresses glycolysis and oxidative phosphorylation in Th17- and Treg-polarizing T cells. Following treatment with itaconate, the S-adenosyl-L-methionine/S-adenosylhomocysteine ratio and 2-hydroxyglutarate levels are decreased by inhibiting the synthetic enzyme activities in Th17 and Treg cells, respectively. Consequently, these metabolic changes are associated with altered chromatin accessibility of essential transcription factors and key gene expression in Th17 and Treg cell differentiation, including decreased RORγt binding at the Il17a promoter. The adoptive transfer of itaconate-treated Th17-polarizing T cells ameliorates experimental autoimmune encephalomyelitis. These results indicate that itaconate is a crucial metabolic regulator for Th17/Treg cell balance and could be a potential therapeutic agent for autoimmune diseases.

The anti-phospholipid syndrome (APS) is characterized by thrombosis and the presence of anti-phospholipid antibodies (aPL). Tissue factor (TF), the major initiator of the coagulation system, is induced on monocytes by aPL in vitro, explaining, in part, the pathophysiology in this syndrome. However, little is known regarding the nature of the aPL-induced signal transduction pathways leading to TF expression. In this study, we investigated aPL-inducible genes in PBMC using cDNA array system and real-time PCR. Our results indicated that the mitogen-activated protein kinase (MAPK) pathway was related to TF expression when PBMCs were treated, in the presence of β₂Glycoprotein I (β₂GPI), with human monoclonal anti-β₂GPI antibodies [β₂GPI-dependent anti-cardiolipin antibodies (aCL/β₂GPI)]. Western blotting studies using monocyte cell line (RAW264.7) demonstrated that p38 MAPK protein was phosphorylated with nuclear factor κB (NF-κB) activation by monoclonal aCL/β₂GPI treatment, and that SB203580, a specific p38 MAPK inhibitor, decreased the aCL/β₂GPI-induced TF mRNA expression. The p38 MAPK phosphorylation, NF-κB translocation and TF mRNA expression triggered by aCL/β₂GPI were abolished in the absence of β₂GPI. These results demonstrated that the p38 MAPK signaling pathway plays an important role in aPL-induced TF expression on monocytes and suggest that the p38 MAPK may be a possible therapeutic target to modify a pro-thrombotic state in patients with APS.

Objectives To evaluate efficacy and safety of combination therapy using certolizumab pegol (CZP) and methotrexate (MTX) as first-line treatment for MTX-naive, early rheumatoid arthritis (RA) with poor prognostic factors, compared with MTX alone. Methods MTX-naive, early RA patients with ≤12 months persistent disease, high anti-cyclic citrullinated peptide, and either rheumatoid factor positive and/or presence of bone erosions were enrolled in this multicentre, double-blind, randomised placebo (PBO)-controlled study. Patients were randomised 1:1 to CZP+MTX or PBO+MTX for 52 weeks. Primary endpoint was inhibition of radiographic progression (change from baseline in modified Total Sharp Score (mTSS CFB)) at week 52. Secondary endpoints were mTSS CFB at week 24, and clinical remission rates at weeks 24 and 52. Results 316 patients randomised to CZP+MTX (n=159) or PBO+MTX (n=157) had comparable baseline characteristics reflecting features of early RA (mean disease duration: 4.0 vs 4.3 months; Disease Activity Score 28-joint assessment (DAS28)) (erythrocyte sedimentation rate (ESR)): 5.4 vs 5.5; mTSS: 5.2 vs 6.0). CZP+MTX group showed significantly greater inhibition of radiographic progression relative to PBO+MTX at week 52 (mTSS CFB=0.36 vs 1.58; p<0.001) and week 24 (mTSS CFB=0.26 vs 0.86; p=0.003). Clinical remission rates (Simple Disease Activity Index, Boolean and DAS28 (ESR)) of the CZP+MTX group were significantly higher compared with those of the PBO+MTX group, at weeks 24 and 52. Safety results in both groups were similar, with no new safety signals observed with addition of CZP to MTX. Conclusions In MTX-naive early RA patients with poor prognostic factors, CZP+MTX significantly inhibited structural damage and reduced RA signs and symptoms, demonstrating the efficacy of CZP in these patients. Trial registration number (NCT01451203).

The pathogenesis of thrombocytopenia in patients with antiphospholipid syndrome (APS) is heterogeneous. Patients with antiphospholipid antibodies (aPL) and thrombocytopenia in the absence of clinical manifestations of APS will be diagnosed and treated as idiopathic thrombocytopenic purpura. However, the presence of aPL places those individuals at particular risk for developing both bleeding and thrombotic complications. Therefore, we propose the inclusion of such patients in the subgroup ‘aPL-associated thrombocytopenia’. More attention should be devoted to this subgroup of patients to elucidate the role of aPL in the development of thrombocytopenia and to facilitate the adequate monitoring of its potential thrombotic risk.