Ab0126 expression of β2 microglobulin in salivary gland epithelial cells of patients with sjogren syndrome

Background Salivary glands epithelial cells (SGECs) activation and loss of homeostasis play a key role in primary Sjogren Syndrome (pSS) [1]. High serum and saliva levels of β2-mycroglobulin (β2-M) have been described [2] in pSS, however, the exact origin of this molecule is still unclear. Our preliminary data from single cell analysis on pSS salivary glands treated with immunosuppressors show a downregulation of this protein in SGECs following treatment. Objectives Aim of this study is to evaluate the expression of β2-M in pSS SGECs and to dissect its modulation in inflammatory conditions. Methods To mimic the inflammatory microenvironment of pSS, a human salivary gland (HSG) cell line was treated (48h) with 1) Poly-I:C (40 μg/ml), 2) LPS (50 μg/ml), 3) culture medium (untreated). The HSG expression of β2-M (Ab anti-β2-M) was evaluated by flow cytometry along with the expression of apoptotic [(annexin V (MBL)] and activation [ICAM-1 (Ab anti-CD54)] molecules. Ex vivo expression of β2-M was then assessed in SGECs deriving from both pSS patients (n=3) and sicca (controls) (n=3). Results In the HSG cell line treated with both Poly I:C and LPS a significant increase in β2-M was documented [mean fluorescence index (MFI): untreated=1 (1-1), Poly-I:C=2.46 (1.5-3.9), LPS=1.3 (1-1.3); p=0.003]. The increased expression of β2-M was paralleled by an increase in ICAM-1 (MFI: untreated=1 (1-1), Poly-I:C=1.61 (1-2.5), LPS=1.26 (1-1.2); p=0.06) and annexin V (mean%: untreated=7.6% (5-9), Poly-I:C=14.3% (9-18), LPS=8% (6-11); p=0.003). In SGECs from pSS a higher expression of β2-M was detected as compared to controls (MFI: pSS=2.5 (2-3) vs sicca=1 (0.5–1.5) (Figure 1). Conclusion Our preliminary data suggest that β2-M is actively expressed by SGECs in pSS and that its exposure is driven by the local inflammatory milieu. Such expression is particularly interesting in view of the already demonstrated capacity of β2-M to activate pro-inflammatory pathways and to influence cellular viability and autoantigens exposure [3]. Functional studies are currently ongoing to dissect the potential pathogenic role of β2-M in pSS. References [1] Colafrancesco S, et al. Arthritis Rheumatol. 2022. [2] Gottenberg JE, et al. PLoS One. 2013. [3] Jin Xie et al. Trends Immunol. 2003. Acknowledgements: NIL. Disclosure of Interests None Declared.