Chemotaxis of Vδ2 T cells to the joints contributes to the pathogenesis of rheumatoid arthritis.

OBJECTIVES: To explore the role of Vδ2 T cells in the pathogenesis of rheumatoid arthritis (RA). METHODS: Sixty-eight patients with RA, 21 patients with osteoarthritis and 21 healthy controls were enrolled in the study. All patients with RA fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA. Peripheral Vδ2T population, chemokine receptor expression and proinflammatory cytokine secretion were quantified by flow cytometry. The infiltration of Vδ2 T cells within the synovium was examined by immunohistochemistry and flow cytometry. The effect of tumour necrosis factor (TNF)-α and interleukin (IL)-6 on Vδ2 T migration was determined by flow cytometry and transwell migration assay. RESULTS: Peripheral Vδ2T cells, but not Vδ1 T cells, were significantly lower in patients with RA, which was negatively correlated with disease activity gauged by Disease Activity Score in 28 joints. Vδ2 T cells from RA accumulated in the synovium and produced high levels of proinflammatory cytokines including interferon-γ and IL-17. Phenotypically, Vδ2 T cells from RA showed elevated chemotaxis potential and expressed high levels of chemokine receptors CCR5 and CXCR3, which was driven by increased serum TNF-α through nuclear factor kappa B signalling. In vivo, TNF-α neutralising therapy dramatically downregulated CCR5 and CXCR3 on Vδ2 T cells and repopulated the peripheral Vδ2 T cells in patients with RA. CONCLUSIONS: High levels of TNF-α promoted CCR5 and CXCR3 expression in Vδ2 T cells from RA, which potentially infiltrated into the synovium and played crucial roles in the pathogenesis of RA. Targeting Vδ2 T cells might be a potential approach for RA.

Identification of Novel Biomarkers for Behcet Disease Diagnosis Using Human Proteome Microarray Approach.

Behcet disease (BD) is a chronic systemic vasculitis and considered as an autoimmune disease. Although rare, BD can be fatal due to ruptured vascular aneurysms or severe neurological complications. To date, no known biomarker has been reported for this disease, making it difficult to diagnosis in the clinics. To undertake this challenge, we employed the HuProt arrays, each comprised of ∼20,000 unique human proteins, to identify BD-specific autoantibodies using a Two-Phase strategy established previously. In Phase I, we profiled the autoimmunity on the HuProt arrays with 75 serum samples collected from 40 BD patients, 15 diagnosed autoimmune patients who suffer from Takayasu arteritis (TA; n = 5)), ANCA associated vasculitis (AAV; n = 5), and Sjogren's syndrome (SS; n = 5), and 20 healthy subjects, and identified 20 candidate autoantigens that were significantly associated with BD. To validate these candidates, in Phase II we constructed a focused array with these 20 candidate BD-associated antigens, and use it to profile a much larger cohort, comprised of serum samples collected from 130 BD patients, 103 autoimmune patients (i.e. 40TA, 40 AAV and 23 SS), and 110 healthy controls. This allowed us to validate CTDP1 (RNA polymerase II subunit A C-terminal domain phosphatase)as a BD-specific autoantigen. The association of anti-CTDP1 with BD patients was further validated using the traditional Western blotting analysis. In conclusion, anti-CTDP1 antibody serves a novel autoantibody for Behcet disease and is expected to help more accurate clinical diagnosis.

[Prevalence of human papillomavirus infection in women in Tibet Autonomous Region of China.].

OBJECTIVE: To determine the prevalence of cervical type-specific human papillomavirus (HPV) infection as well as risk factors associated in Tibet Autonomous Region of China. METHODS: A cluster sampling study was performed in Lasa, Rikaze and Naqu of Tibet. An epidemiological questionnaire was applied and 3036 cervical specimens were obtained for liquid-based cytology and HPV DNA detection. Statistical analysis included Wald Chi-square and stepwise logistic regression model. RESULTS: The overall HPV prevalence of involved 3036 women was 9.19% (279/3036), of which 7.05% (214/3036) of the women were infected by high-risk types (including 14 sorts of types) and 2.14% (65/3036) by low-risk types (including 6 sorts of types). There were no significant differences of HPV prevalence between age groups (P = 0.936), race (P = 0.718) and areas (P = 0.746), respectively. Twenty-one types of HPV were detected, of which HPV16 (1.52%) was the most common type, followed by HPV33 (1.42%), HPV58 (1.22%), HPV52 (1.15%), and HPV31 (1.05%). HPV type distribution was varied by age. Of the 279 HPV infected women, 14.3% (40/279) exhibited multiple HPV infections. Independent risk factors for HPV infection were smoking (P = 0.027), number of sex partners (P = 0.198) and early age of first intercourse (P = 0.237). CONCLUSION: The overall prevalence of HPV infection in Tibet Autonomous Region is lower than that in China or abroad, in which the most common genotype is HPV16 and the independent risk factors for HPV infection included early age of first intercourse, smoking, and number of sex partners.