AB1066 TO STUDY THE CORRELATION OF IL-33/ST2 EXPRESSION WITH CLINICAL AND LABORATORY CHARACTERISTICS OF NON-RENAL MANIFESTATIONS OF SYSTEMIC LUPUS ERYTHEMATOSUS-A PROSPECTIVE, OBSERVATIONAL, CROSS-SECTIONAL STUDY
Authors: S. Manna, V. S. Pai, M. O. Pai, V. K. Bhogaraju, A. Baweja, A. Gupta
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> SLE is the prototype systemic autoimmune inflammatory disorder with significant morbidity and mortality. Despite our increased understanding, new molecular pathways are still under investigation for accurate disease activity measures and disease-specific treatment. IL-33, a novel member of the IL-1 family, and its receptor ST2, (both membrane-bound form and a soluble form), have gained increasing recognition in the pathogenesis of various immune-mediated diseases like SLE. <h3>Objectives:</h3> The study was conducted to assess the expression of pleiotropic cytokine IL-33/ST2 axis in non-renal lupus patients and to determine its correlation with various clinical characteristics and laboratory parameters. <h3>Methods:</h3> We carried out the present study at All India Institute of Medical Sciences, Rishikesh, tertiary-level referral center in North India, from November 2020 to April 2022. Based on SLICC criteria, we selected 32 SLE patients and 15 healthy volunteers for comparison. We divided the patients into two groups according to the SLEDAI value: the active disease group [SLEDAI &gt;5 (21/32)] and the low disease activity or remission group [SLEDAI ≤5 (11/32). We extracted RNA from standard Ficoll Hypaque density gradient centrifugation derived peripheral blood mononuclear cells (PBMCs) using an RNA isolation kit from Qiagen and then prepared cDNA using a reverse transcription cDNA prep kit from Qiagen. Real-Time PCR was conducted using SyBr PCR mix with GAPDH, IL-33, and ST2 primer. We computed the final gene expression from the result of the real-time PCR for IL-33/ST2 using the Livak method of relative gene expression. We measured protein expression of IL-33 and sST2 in serum by sandwich ELISA using monoclonal antibodies by R and D® Systems. Finally, we tabulated clinical characteristics (categorical) and lab parameters (numerical) data and analyzed using appropriate statistical tests in SPSS 23.0 software. <h3>Results:</h3> The study population had a female predominance pattern (Female: Male = 6:1) with a mean age of 32±12.49 years. Apart from constitutional symptoms, commonly affected organ systems were mucocutaneous, joints, respiratory, and hematopoietic systems. Regardless of the level of disease activity, SLE patients had increased serum sST2 (P &lt;.001) and IL33 mRNA expression in PBMC than healthy controls (p =.01). However, we found no significant difference in serum IL-33 levels (P =.312) and ST2 gene expression (P =.525). Compared to their counterparts, patients with autoimmune hemolytic anemia had greater serum levels of IL-33 (P &lt;.001). The presence of active arthritis positively correlated with IL-33 gene expression (P =.035). We failed to establish a significant correlation between most of the laboratory parameters and IL-33/ST2 gene expression or their corresponding serum expression except anti-ds DNA positivity that showed a trend towards higher mean ST2 gene expression (P =.05). <h3>Conclusion:</h3> We found significantly higher expression of the IL-33 gene and serum ST2 levels in non-renal SLE patients compared to age and sex-matched healthy controls. Although the majority of clinical, laboratory, or disease activity markers did not correlate with IL-33/ST2 expression, it does provide preliminary information on the pattern of IL-33/ST2 expression in the Asian population that will open the door for a more structured study design to gain more understanding of our main research question. <h3>REFERENCES:</h3> [1] Manetti M, Ibba-Manneschi L, Liakouli V, Guiducci S, Milia AF, Benelli G, et al. The IL1-like cytokine IL33 and its receptor ST2 are abnormally expressed in the affected skin and visceral organs of patients with systemic sclerosis. Ann Rheum Dis. 2010 Mar 1;69(3):598–605. Table 1 shows the serum IL-33 and serum soluble ST2 among the study population. No significant difference was noted in the expression of serum IL-33 among Active disease, Low disease activity/remission, and the control group. Serum ST2 level was significantly higher among all SLE patients irrespective of disease activity than in healthy controls. However, no significant difference was noted in serum ST2 levels among active SLE and SLE with low disease activity or in the remission group <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>