Expressions And Clinical Significance Of OX40and PD1in Patients With Primary Sj(o|¨)gren’s Syndrome

Primary Sj gren’s syndrome (pSS) is a systemic autoimmune disease in which animmunological attack primarily against the salivary and lacrimal glands results in theloss of acinar cell tissue and function, leading to stomatitis sicca andkeratoconjunctivitis sicca. pSS may also affect other organs, leading to multiple organinjury. Its etiology is unknow, reported that the activation of CD4+T cells and B cells isconsidered to play a critical role in pSS.Costimulatory molecules play a key role in the activation of T cell. According tothe function of immune response effect, Costimulatory molecules can be divided intopositive molecules and negative molecules. The positive costimulatory moleculesprovides stimulatory signal that promotes antigen-specific T cell proliferation,activation and cytokine secretion,leading to autoimmune disease; While negativecostimulatory molecules which inhibits T-cell proliferation, cytokine production, iscritical for the termination of immune responses,for perpheral tolerance. OX40and itsligand OX40L, are members of TNF/TNFR super-family. OX40/OX40L interactionshave been shown to be crucial for the generation of memory T cells and survival, andfor T cell activation. Programmed death-1(PD-1, CD279) is a member of CD28superfamily of immunoreceptors. Signaling through PD-1inhibits T-cell proliferation,cytokine production.Previous studies have confirmed that abnormal PD-1and OX40signals areassociated with autoimmunity.Therefore, In our study, The expression of OX40andPD-1were detected by flow cytometry and analyse its relationship with clinicalcharacteristics in pSS. We inferred that abnormal PD-1and OX40signals may beinvolved in the immunopathogenesis of pSS. PART I: Expressions and clinical significance of OX40andOX40L in patients with primary Sj gren’s syndromeObjective: To investigate the expression of costimulatory molecules OX40andOX40L on peripheral blood mononuclear cells (PBMC) and its relationship withclinical characteristics in primary Sjogren’s syndrome (pSS).Methods: Peripheral blood samples were collected from51pSS patients and36healthy subjects (HC). The expression of OX40and OX40L on PBMC were detected byflow cytometry.Results: The expression of OX40on CD4+T cells in pSS patients wassignificantly higher than that in the HC group (8.65%±3.51%vs5.68%±1.68%, P<0.01). However, there was no significant difference in OX40expression on CD8+Tcells between patient group and HC group. In comparison with HC group, theexpression of OX40L on monocytes (6.76%±3.60%vs3.15%±1.89%, P <0.01)and Bcells (4.69%±2.40%vs2.76%±1.33%, P <0.01) was significantly increased in pSSpatients. Moreover, OX40expression on CD4+T cells and OX40L expression onmonocytes and B cells were significantly increased in active pSS patients comparedwith those in inactive patients. The expression levels of OX40and OX40L were higherin pSS patients with multiple system damage than in patients with simple exocrinegland injury. In addition, immunosuppressive therapy significantly reduced theexpression of OX40and OX40L.Conclusion: The expression of OX40and OX40L on peripheral lymphocytes wasupregulated in pSS patients. The high levels of OX40and OX40L expressionsignificantly correlated with clinical outcome and therapeutic response, suggesting thatOX40/OX40L pathway may play a critical role in pSS pathogenesis.PART II: Expressions and clinical significance of PD-1and PD-L1in patients with primary Sj gren’s syndromeObjective: To investigate the expression of costimulatory molecules PD-1andPD-L1on peripheral blood mononuclear cells (PBMC) and its relationship with clinical characteristics in primary Sjogren’s syndrome (pSS).Methods: Peripheral blood samples were collected from51pSS patients and36healthy subjects (HC). The expression of PD-1and PD-L1on PBMC were detected byflow cytometry.Results:(1) Compared with healthy controls, the expression of PD-1on CD4+Tcells(29.3%±7.90%vs23%±4.50%, P <0.05) and on CD8+T cells（21.2%±7.10%vs16.6%±5.80%，P <0.05） was significantly increased in pSS patients, the expressionof PD-L1on CD14+monocytes was decreased (17%±9.50%vs23.6%±11.7%, P<0.01), but no significant difference in PD-L1expression on CD19+B lymphocytes. Theexpression of PD-1on CD4+T was significantly higher in active PSS patients thaninactive patients, immunosuppressive therapy significantly reduced the expression ofPD-1, but there was no significant correlation with tissue damage. PD-1expression onCD8+T cell and PD-L1expression on monocytes and B cells were no significantcorrelation with disease severity, system damage and therapy effects.(2) The level ofserum sPD-1in patients with pSS was significantly higher than that in healthy controlgroup ((0.37±0.30) μg/ml vs (0.20±0.10) μg/ml,(P <0.05). Compared with inactivepatients, The level of serum sPD-1was significantly higher in active pSS patients; Thelevel of sPD-1was significantly higher in patients with multiple system injury than inpatients with simple exocrine gland injury. And before and after the treatment, the levelof sPD-1had no difference.Conclusion: The abnormal expression of PD-1and PD-L1was detected on PBMC inpSS patients. The abnormal expression of PD-1and PD-L1was correlated withdisease activity and tissue injury,which suggest that disorders of PD-1/PD-L1signalsmay play a critical role in pathogenesis of pSS.