Abstract
IntroductionPrimary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells. This study was to investigate the correlation of peripheral granzyme B (GranzB)-expressing CD4+ T cells with disease severity and histological lesion in patients with pSS.MethodsWe recruited 116 pSS and 46 health control (HC) using flow cytometry to examine the percentage of CD4+GranzB+CTLs in the peripheral blood, and immunofluorescence to test their expression in the labial gland.ResultsThe percentage of CD4+GranzB+CTLs was significantly upregulated in pSS than in HC (7.1 ± 4.9% vs 3.1 ± 1.9%, p < 0.0001) and positive correlation with ESSDAI. The frequency of them was 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 cutoff point was 4.865 for pSS patients.ConclusionIn this study, we provide new evidence indicating the 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.
Highlights
Primary Sjögren’s syndrome is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells
Large histopathological evidences found most of T cells infiltrated in the minor salivary glands (MSG) of Primary Sjögren’s syndrome (pSS) patients are CD4+ T cells, distributed at the periphery of the lesion, and their number is decreasing with infiltrate severity ranging from 57% of total T cells in advanced lesions to 70% in mild lesion, whereas B lymphocytes are increased and located centrally or within ectopic germinal center (GC) [8]
The percentage of CD4+granzyme B (GranzB)+cytotoxic T lymphocytes (CTLs) was significantly upregulated in pSS patients than in healthy controls and positive correlation with ESSDAI in pSS patients but had no correlation with ESSPRI One hundred and sixteen pSS patients and 46 healthy controls were recruited in this study
Summary
Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells. Large histopathological evidences found most of T cells infiltrated in the MSG of pSS patients are CD4+ T cells, distributed at the periphery of the lesion, and their number is decreasing with infiltrate severity ranging from 57% of total T cells in advanced lesions to 70% in mild lesion, whereas B lymphocytes are increased and located centrally or within ectopic germinal center (GC) [8]. It follows that CD4+ T lymphocytes may be the initial cells at the early stage of immune response in the pathogenesis of pSS. These cells were known about as direct effectors in anti-tumor immunity and viral infections through their perforin/granzyme-mediated cytolytic activity and contribute to cytolysis of tumors or virally infected targets [10]
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