Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients.

OBJECTIVES: To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. METHODS: Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. RESULTS: Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P = 0.005), CRP (AUC = 0.75; P = 0.017), and ASDAS (AUC = 0.778, P = 0.007) significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P = 0.040) significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ(2) = 6.87, P = 0.009, and wald χ(2) = 5.171, P = 0.023). CONCLUSIONS: Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients.

[Efficacy and safety of infliximab in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the efficacy and safety of Infliximab (IFX) plus methotrexate (MTX) combination therapy in patients with rheumatoid arthritis (RA). METHODS: Prospectively observe refractory RA patients who were treated with combination therapy of MTX and IFX. IFX was infused at the dosage of 3 mg/kg, in week 0, 2, 6, and then every 8 weeks. During treatment, clinical variables, disease activity and adverse effects were evaluated. RESULTS: After treatment, 69.8%, 52.4%, 29.5% and 7.2% RA patients achieved ACR20, ACR50, ACR70 and ACR90 respectively. There were significant statistical differences in the changes of swollen joint counts, tender joint counts, VAS scale, patient' s global assessment, and physician's global assessment before and after therapy. CONCLUSION: Infliximab plus MTX achieved significant efficacy and safety in refractory RA patients.

Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway.

Autoantibodies to proteinase 3 (PR3) are involved in the pathogenesis of autoimmune-mediated vasculitis in Wegener granulomatosis (WG). To address the question how the autoantigen PR3 becomes a target of adaptive immunity, we investigated the effect of PR3 on immature dendritic cells (iDCs) in patients with WG, healthy blood donors, and patients with Crohn disease (CD), another granulomatous disease. PR3 induces phenotypic and functional maturation of a fraction of blood monocyte-derived iDCs. PR3-treated DCs express high levels of CD83, a DC-restricted marker of maturation, CD80 and CD86, and HLA-DR. Furthermore, the DCs become fully competent antigen-presenting cells and can induce stimulation of PR3-specific CD4(+) T cells, which produce IFN-gamma. PR3-maturated DCs derived from WG patients induce a higher IFN-gamma response of PR3-specific CD4(+) T cells compared with patients with CD and healthy controls. The maturation of DCs mediated through PR3 was inhibited by a serine protease inhibitor, by antibodies directed against the protease-activated receptor-2 (PAR-2), and by inhibition of phospholipase C, suggesting that the interactions of PR3 with PAR-2 are involved in the induction of DC maturation. Wegener autoantigen interacts with a "gateway" receptor (PAR-2) on iDCs in vitro triggering their maturation and licenses them for a T helper 1 (Th1)-type response potentially favoring granuloma formation in WG.

Transfer of human leukocytes into double-knockout Pfp-/-Rag2-/- mice grafted with human skin: increased accumulation of neutrophils in human dermal microvessels.

Severe combined immunodeficient mice reconstituted with human leukocytes have been useful to model parts of the human immune system, including some of its diseases (e.g., AIDS). Because no human polymorphonuclear leukocytes (huPMN) develop in these xenograft models, diseases such as several forms of vasculitis cannot be modeled using this approach. To provide such a model for vasculitis, human skin patches were grafted onto double-knockout Pfp(-/-)Rag2(-/-) mice, which not only lack functional T and B cells but which are also devoid of natural killer cells. After intravenous injection, a high proportion of huPMNs survived within the circulation and accumulated in the human blood vessels. The accumulation increased considerably after the endothelium of the skin patches had been stimulated by tumor necrosis factor-alpha. Alpha mild perivascular neutrophilic infiltration and vascular necrosis was observed in the microvessels of the skin patches. Thus, a xenograft model of vasculitis with predominant huPMNs infiltration has been established for the first time.

[Clinical analysis of 61 patients with antiphospholipid syndrome].

OBJECTIVE: To investigate the clinical manifestations, diagnosis and treatment of anti-phospholipid syndrome (APS). METHODS: 61 patients with defined APS admitted from Jan 1986 to Dec 2002 were analyzed retrospectively. RESULTS: 10 patients with primary APS and 51 patients with secondary APS were analyzed. Women were affected 3.1 times as that of men. 48 of the 51 (94.1%) patients with secondary APS were complicated with other autoimmune diseases, including 33 cases (64.7%) of systemic lupus erythematosus. Vascular thrombosis was presented in around 80.3% of the patients in this study. Thrombosis frequently involved the gastrointestinal system (21 cases, 22.6%), pulmonary system (19 cases, 20.4%), the cerebral vascular system (17 cases, 18.3%), lower limb deep venous system (16 cases, 17.2%), and infrequently coronary arteries or adrenal glands. The abnormal pregnancy rate in the 37 married women was 45.9%. The prevalence of anticardiolipin antibody (ACL) and lupus anticoagulant (LA) was 77.0% and 62.3% respectively. LA was associated with ACL. CONCLUSION: APS occurs most commonly among young women, is a disorder characterized by recurrent venous or arterial thrombosis and/or fetal losses associated with positive ACL or LA. Thrombosis frequently occurs in gastrointestinal system, pulmonary system, cerebral vascular system and deep venous system. The association between clinical features of APS and antiphospholipid antibody is significant. LA is a stronger risk factor for thrombosis and abnormal pregnancy than ACL. Antiplatelet with low-dosage aspirin and long-term anticoagulation are main therapeutics.

Diagnostic value of anti-cyclic citrullinated Peptide antibody in patients with rheumatoid arthritis.

OBJECTIVE: To explore the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) detected by ELISA in patients with rheumatoid arthritis (RA). METHODS: The synthesized cyclic citrullinated peptide was used as substrate for ELISA. Anti-CCP antibody was detected by ELISA in 191 patients with RA, 132 with rheumatic diseases other than RA, and 98 with nonrheumatic diseases. The antiperinuclear factor (APF), anti-keratin antibody (AKA), rheumatoid factor (RF), and HLA-DR4 gene complex were also tested in each RA patient. The results of these tests were compared with anti-CCP antibody to examine the correlation between them. RESULTS: Ninety (47.1%) patients with RA, 4 (3.0%) with other rheumatic diseases, and 2 (2.0%) with nonrheumatic diseases were found to be anti-CCP antibody positive by ELISA. The sensitivity of anti-CCP antibody was 47.1%, with a high specificity (97.4%) in RA. Anti-CCP antibody correlated with APF, AKA, RF, and HLA-DR4 gene complex. CONCLUSION: A new modified anti-CCP antibody test had a moderate sensitivity (47.1%) but a high specificity (97.4%) in patients with RA and was found as a valuable supplement to diagnosis of RA. Anti-CCP correlated with APF, AKA, RF, and HLA-DR4 gene complex, but did not completely overlap with them. Anti-CCP antibody could be regarded as a new diagnostic marker for RA.