Utility of lymphocyte phenotype profile to differentiate primary Sjögren’s syndrome from sicca syndrome

Rheumatology ◽  
2021 ◽  
Author(s):  
José Loureiro-Amigo ◽  
Carlos Palacio-García ◽  
Mónica Martínez-Gallo ◽  
Fernando Martínez-Valle ◽  
Marc Ramentol-Sintas ◽  
...  

Abstract Objective To assess the potential diagnostic utility of advanced lymphocyte profiling to differentiate between primary Sjögren’s Syndrome (pSS) and non-Sjögren Sicca syndrome. Methods Distribution of peripheral lymphocyte subpopulations was analysed by flow cytometry in 68 patients with pSS, 26 patients with sicca syndrome and 23 healthy controls. The ability to discriminate between pSS and sicca syndrome was analysed using the area under the curve (AUC) of the receiver operating characteristic curve of the different lymphocyte subsets. Results The ratio between naïve/memory B cell proportions showed an AUC of 0.742 to differentiate pSS and sicca syndrome, with a sensitivity of 76.6% and a specificity of 72% for a cut-off value of 3.4. The ratio of non-switched memory B cells to activated CD4+ T cells percentage (BNSM/CD4ACT) presented the highest AUC (0.840) with a sensitivity of 83.3% and specificity of 81.7% for a cut-off value <4.1. To differentiate seronegative pSS patients from sicca patients, the BNSM/CD4ACT ratio exhibited an AUC of 0.742 (sensitivity 75%, specificity 66.7%, cut-off value <4.4), and the number of naïve CD4 T cells had an AUC of 0.821 (sensitivity 76.9%, specificity 88.9%, cut-off value <312/mm3). Conclusion Patients with pSS show a profound imbalance in the distribution of circulating T and B lymphocyte subsets. The ratio BNSM/CD4ACT is useful to discriminate between pSS and sicca syndrome.

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Qi Wang ◽  
Nan Che ◽  
Chengyin Lu ◽  
Xiaoxuan Sun ◽  
Yanyan Wang ◽  
...  

Abstract Introduction Primary 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. Methods We 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. Results The 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. Conclusion In 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.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1032.1-1033
Author(s):  
J. Y. Yang ◽  
S. X. Zhang ◽  
L. Hao ◽  
Q. Y. Su ◽  
J. Bai ◽  
...  

Background:Primary Sjögren’s syndrome (pSS) is a chronic inflammatory autoimmune disease mainly involving exocrine glands and involving multiple organs and systems1. Recent studies have reported that peripheral lymphocyte subsets such as Th1, Th2, Th17, and regulatory cells (Tregs), have been implicated in the pathogenesis of pSS2. However, the detailed statuses of lymphocyte subsets of pSS patients remain to be clearly evaluate and effects of immunomodulatory therapies on the lymphocyte subsets are unknown.Objectives:To explore the pathogenesis and evaluate the therapeutic effect of immunomodulatory drugs (IMiDs) by comparing the changes of lymphocyte subsets in peripheral blood (PB) before and after treatment.Methods:This study included 1,221 pSS patients and 206 healthy controls (HCs). Among these patient, 759 patients were received our new immunoregulatory therapies such as low-dose interleukin-2, rapamycin, metformin, retinoic acid etc. The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and Tregs in PB of these subjects were detected by flow cytometry combined with standard absolute counting beads. Data were expressed as mean ± standard deviation to the distribution. Independent-samples T test and paired-samples T test were applied.Pvalue <0.05 were considered statistically significant.Results:The absolute numbers of circulating Tregs as well as T, NK cells in pSS patients were significantly lower than those of HCs (P<0.05). After immunoregulatory combination treatments, the number of Tregs was significantly increased (P<0.05). Though the absolute numbers of T, NK, CD4+T, CD8+T, Th1, and Th17 cells were also increased to some degree (P<0.05), the increased amount of Tregs was much more than other cells, resulting a new balance between pro- and anti- inflammatory lymphocyte homeostasis.Conclusion:The decrease of peripheral Tregs played an important role in the pathogenesis of primary Sjögren’s syndrome. Immunoregulatory combination therapies promoted the increase of Tregs and might help for the recovery of pSS.References:[1]Mariette X, Criswell LA. Primary Sjogren’s Syndrome. N Engl J Med 2018;378(10):931-39. doi: 10.1056/NEJMcp1702514 [published Online First: 2018/03/08][2]Miao M, Hao Z, Guo Y, et al. Short-term and low-dose IL-2 therapy restores the Th17/Treg balance in the peripheral blood of patients with primary Sjogren’s syndrome. Ann Rheum Dis 2018;77(12):1838-40. doi: 10.1136/annrheumdis-2018-213036 [published Online First: 2018/06/25]Acknowledgments :None.Disclosure of Interests:None declared


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