Evaluation of the frequency and intensity of COVID-19 in patients with ankylosingspondylitis under anti-TNF therapy

Abstract

BACKGROUND: The underlying pathogenetic mechanisms of Sjögren syndrome (SjS) have not been elucidated yet [1]. Leptin is a glycosylated peptide structurally similar to some cytokines [2]. Leptin has proinflammatory effects via various mechanisms. It has been previously reported that serum leptin levels increase in some autoimmune diseases and that leptin levels are also associated with disease activity [3, 4]. In addition, leptin and its receptor in the salivary glands stimulate epithelial proliferation and modulate the local immune system with their autocrine effects [5]. In this study, we assessed the presence of leptin in minor salivary glands (MSG) of the patients with and without SjS. Additionally, we evaluated the association between leptin staining intensity and disease activity among patients with SjS. We included patients who underwent MSG biopsy with the suspicion of SjS between 2013 and 2014. Among these patients, those who met the 2012 American College of Rheumatology Sjögren's syndrome classification criteria (6) and had at least 50 mononuclear cell infiltrates in a 4 mm2 minor salivary gland section were classified as the SjS group. The rest of the patients who underwent MSG biopsy but did not meet the histopathological and/or clinical criteria for SjS were considered the control group. Leptin staining was assessed by immunohistochemistry (Bio-Rad AbDSerotec, Oxford, UK) in the stroma, acinar and ductal epithelium, and staining intensities were graded by a semiquantitative method; no staining (score 0), mild (score 1), moderate (score 2), and diffuse (score 3). Definitions of leptin staining intensities were described as mild; focal staining of few cells in one focus, moderate; mild staining in more than one focus, diffuse; diffuse staining in all assessed sections (Figure 1). The sum of leptin staining in all areas was defined as total leptin staining. The SjS group was divided into 3 groups according to the focus scores (FS) (FS1: FS = 1, FS2: FS = 2, FS3: FS ≥ 3). In addition, patients' disease activities were assessed by EULAR Sjogren's syndrome disease activity index (ESSDAI) [7]. Visual (histograms, probability plots) and analytical methods (Kolmogorov-Smirnov test) were used to analyze the variables' distribution and select the test method. Descriptive analyses were presented as mean or median according to their distribution patterns. A chi-square test was used for univariate analyses to identify variables associated with leptin staining and clinical features. Patients' disease activities were assessed by ESSDAI [9]. The correlations between ESSDAI scores and leptin staining intensities were analyzed using Spearman's test. A p value of 66%, in FS3 group: 100%) areas were higher in the patients with FS3. There was a positive correlation between ESSDAI and leptin staining scores in the acinar area (p < 0.05; r = 0.406) regardless of focus scores. However, the correlations between disease activity and leptin staining in ductal areas (p: 0.1; r: 0.334), in stromal areas (p: 0.1; r: 0.184), and total leptin (p: 0.2; r: 0.268) staining was not significant. We identified that majority of the patients in both groups had leptin staining in acinar (92% and 84%, respectively), ductal (94% and 84%, respectively), and stromal areas (96% and 100%, respectively) of their MSGs. Patients with higher FSs had significantly more intense leptin staining patterns. The possible explanations for the similar staining pattern in patients with an FS of ≤2 was the insufficient number of patients (β error) or absolute indifference. In contrast, a study by Erbasan F et al. argued that leptin has no role in primary SjS due to similar leptin staining patterns among patients with SjS and healthy controls. However, they did not compare patients according to the ESSDAI scores [8]. Thus, we still need more robust data to identify whether leptin has an inciting or prognostic role in pSS. Limitations of our study were the lack of some clinical characteristics and metabolic parameters which may affect leptin metabolism and lack of leptin receptor staining patterns in MSG biopsies, which together with leptin staining could better define the role of leptin. Lack of power analysis was another limitation. In conclusion, leptin staining properties were similar in both SjS and non-SjS groups. Additionally, the only clinical significance of leptin density in the MSG was in the acinar region. RESULTS: The authors have no financial or competing interests. DISCUSSION: All authors declare no conflict of interest We received funding support from Kartal Dr. Lutfi Kirdar City Hospital research assistance department. Authors contributed to writing this study and have approved the final version. Ethical approval: This article does not contain any studies with human participants performed by any of the authors. The study protocol was approved by the Local Ethics Committee of Dr Lutfi Kirdar Kartal City Hospital.