AB0135 ASSOCIATION OF STAT1, STAT4 AND JAK2 IMMUNOEXPRESSION WITH THE GRADE OF MONONUCLEAR CELL INFILTRATION IN MINOR SALIVARY GLAND BIOPSIES IN PATIENTS WITH PRIMARY SJOGREN’S SYNDROME

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; p. 1247
• Main Authors: Maślińska, M., Grabowska, M., Wajda, A., Kostyra-Grabczak, K., Paradowska-Gorycka, A.
• Format: Journal Article
• Language: English
• Published: Kidlington BMJ Publishing Group Ltd and European League Against Rheumatism 01.06.2023; Elsevier B.V; Elsevier Limited
• Subjects: Biopsy; Exocrine glands; Gene expression; Image processing; Infiltration; Janus kinase; Janus kinase 2; Kinases; Monoclonal antibodies; Pathogenesis; Prognostic factors; Protein-tyrosine kinase receptors; Salivary gland; Scientific Abstracts; Signal transduction; Sjogren's syndrome; Sjögren syndrome; Stat1 protein; Stat4 protein; Statistical analysis; Transcription; α-Interferon; β-Interferon; γ-Interferon; Sjögren syndrome; Prognostic factors
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.3300

BackgroundSignal transducer and activator of transcription 4 (STAT4) is an important for Interferon-γ induction (type 2 IFN signaling). Whereas type 1 IFN signaling pathway depends on signal transducer and activator of transcription 1 (STAT1) and Janus kinase 2 (JAK2). JAK2 is a non-receptor tyrosine kinase that plays a role in signal transduction via others type II receptors including IFN-α, IFN-ß, IFN-γ. The IFN signature in Sjogren’s syndrome and overexpression of IFN-1 and IFN-2 in minor salivary glands biopsies (MSGBs) were described.ObjectivesThe aim of the study was to analyze the immunoexpression of STAT4, STAT1 and JAK2 in biopsies of MSG depending on the severity of mononuclear cell infiltration (focus score, FS) in patients with primary Sjogren’s syndrome(pSS).MethodsThe study group consisted of 64 patients with pSS aged 48.25±16.47. 89% of the subjects were women. MSGBs were routinely stained with HE for conventional histopathological examination with determination of FS. Monoclonal antibodies were used to determine the immunoexpression of the STAT1, STAT4, and JAK2,Quantitative Computer Image Analysis of Immunoexpression (ScanScope AT2 scanner) has been conducted. The percentage of positive immunostaining for each protein was determined in 20 HPF in each group of patients according to FS. Results were analyzed using TIBCO Statistica v. 13.3 Obtained values failed normal distribution assumption, therefore the non-parametric Kruskal–Wallis test with Dunn’s multiple comparison test for post hoc analysis was used to assess the differences between the groups. p < 0.05 were considered to be statistically significant.Results33% pSS patients were characterized by FS=1; 30%-FS= 3; FS=0 - 9%; 3% and 2% of patients revealed FS=5 and FS=6, respectively. In MSGBs JAK2-, STAT1-, and STAT4-immunopositive cells were observed. The various nuclear and cytoplasmic immunoexpression of JAK2, STAT1 and STAT4 in acinar and ductal cells and also in lesions displaying immune-cell infiltration were observed. However the immunoexpression of STAT4 in the nucleus was relatively rarely found. The percentage of JAK2-, STAT1- and STAT4-positive cells in FS = 0 was significantly lower in comparison with FS equal or greater than 3. However for STAT4, already in FS=2 there was a stronger signal compared to FS=0. The percentage of JAK2- and STAT1-positive cells in MSG in FS = 0 was statistically insignificant in comparison with FS = 1 and 2. There was no statistical significance in the percentage of STAT4- positive cells in patients with FS = 0 in comparison with FS = 1 (Figure 1). mRNA level of STAT4 in whole blood in patients with pSS revealed the opposite trend. The increase of FS was correlated with the decreased mRNA level of STAT4.Figure 1.The percentage of JAK2-, STAT1- and STAT4-immunopositive cells in the human labial salivary glands according to the focus score (FS 0, FS 1, FS2, FS 3, FS 4, FS 5, FS 6) in the patients with pSS ** p < 0.05 vs. F0 group; * p < 0.001 vs. F0 groupConclusionNotably, in the case of STAT4 immunoexpression increased with increasing FS. Interestingly, mRNA level of STAT4 determined in the whole blood decreased with increasing FS (data not shown).The question remains why the immunoexpression of STAT4 in nucleus was relatively rarely found, and what is the impact of the dynamics of STAT4-dependent gene expression on the pathogenesis of pSS. In studied patients STAT4 activity dominates in MSG infiltrates which confirms the role of this factor in the pathogenesis of pSS.References[1]Bromberg J, Darnell JE Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene. 2000;15;19(21):2468-73. doi: 10.1038/sj.onc.1203476[2]Gandolfo S, Ciccia F. JAK/STAT pathway targeting in primary Sjögren syndrome. Rheum. Immun. Res. 2022;3 (3):95-102. doi: 10.2478/rir-2022-0017Acknowledgements:NIL.Disclosure of InterestsNone Declared.