Cellular composition of the minor salivary gland inflammatory infiltrates as an additional diagnostic criterion for primary Sjogren’s syndrome

Abstract

Primary Sjogren’s syndrome (pSS) is one of the most frequent among the connective tissue diseases. Histological examination of the minor salivary gland (MSG) is important diagnostic method. The currently established histological criteria for pSS do not have absolute sensitivity and specificity, which makes the search for additional morphological hallmark relevant.Aim – to study of the qualitative and quantitative composition of cellular populations inflammatory infiltrates in MSG pSS patient with the assessment of additional diagnostic criteria for disease based on the data obtained.Subjects and methods. The study included 55 patients with a diagnosis of pSS according to the criteria of ACR/ EULAR 2016. The control group consisted of 18 healthy volunteers. A MSG biopsy was performed all subjects for histological and immunohistochemical studies with a quantitative assessment of CD3+, CD4+, CD8+, CD20+, CD21+, CD68+, CD138+ cells. Statistical data analysis was performed using the Statistica 10.0 for Windows (StatSoft Inc., USA). For comparison of quantitative traits, the Mann – Whitney U-test was used. To determine the diagnostic threshold of the number of a ROC analysis was performed. An operating characteristic curve was plotted. The area under the curve (AUC), diagnostic specificity, diagnostic sensitivity, diagnostic accuracy, likelihood ratio of the positive and negative results of the test were calculated. The construction of classification models, including the number of different cell types, was carried out using linear discriminant analysis.Results and discussion. The number of CD3+, CD4+, CD8+, CD20+, CD138+ cells in 4 mm2 (area of section) was significantly higher in the pSS group. The largest AUC were observed for the quantitative evaluation of CD3+ cells – 0.88 [95% confidence interval (CI): 0.80–0.96] and CD8+ cells – 0.87 [95% CI: 0.79–0.95], which at the specified diagnostic thresholds corresponded to the sensitivity of 70.9% [95% CI: 57.86–81.23] and 65.45% [95% CI: 52.25–76.64], specificity of 94.4% [95% CI: 74.24–99.72] and 100% [95% CI: 82.41–100], respectively. The CD21+ follicular dendritic cells were detected only in MSG of pSS group. AUC for quantitative assessment of these cells was 0.65 [95% CI: 0.52–0.78], sensitivity 29.1% [95% CI: 18.77–42.14] and specificity 100% [95% CI: 82.41–100]. Using the method of discriminant analysis, we designed classification models that included various combinations of the studied markers. The highest AUC among all possible combinations was observed for the decimal logarithms of the number of CD3+ and CD68+ cells – 0.92 [95% CI: 0.85–0.98], which for a given diagnostic threshold corresponded sensitivity – 81.82% [95% CI: 69.67–89.81], specificity – 94.4% [95% CI: 74.24–99.72].