Correlation of Peripheral CD4+GranzB+CTLs with Disease Severity in Patients with Primary Sjögren’s Syndrome

Abstract Introduction: The major histopathologic lesion of SS is a focal lymphocytic infiltrate, which include a majority of CD4+T. Several studies have shown that the epithelial cells in SS present diverse phenomena, such as MHC class II overexpression. CD4+T cells with cytotoxic activity are characterized by their ability to secrete granzyme B to kill the target cells in an MHC class II-restricted fashion. So this study was to investigate the correlation of peripheral CD4+GranzB+CTLs with pSS. Methods: We recruited 116 pSS and 46 HC using flow cytometry to examine the percentage of CD4+GranzB+CTLs in peripheral blood, and immunofluorescence to test their expression in labial gland. Results: The percentage of CD4+GranzB+CTLs were significantly up-regulated in pSS than HC (7.1±4.9% vs 3.1±1.9%, p <0.0001) and positive correlation with ESSDAI. The frequency of them were markedly higher in pSS with extraglandular manifestations. After excluding the other risk factors associated with pSS, they were still related to ESSDIA and extraglandular manifestations independently(p<0.05) and they are the risk factor of extraglandular involvement (odds ratio=1.928). Moreover, They could be observed in the LSGs. ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS, and 0.851 to presume extraglandular manifestations. The best diagnostic cut-off point was 4.865 for pSS patients. Conclusion: In this study, We provide new evidence indicating involvement of CD4+GranzB+CTLs over activation in the pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.