Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 04 1 16 Zeinab Baghernejadan Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Nahid Kianmehr Department of Rheumatology, Iran University of Medical Sciences, Tehran, Iran Anousheh Haghighi Department of Rheumatology, Iran University of Medical Sciences, Tehran, Iran Mohammad-Ali Assarehzadegan Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Ali-Akbar Delbandi Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Fatemeh Afrashteh Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Zahra Saleh Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Milad Karimi Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Reza Falak Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Majid Khoshmirsafa Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran AND Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran 2026 04 25 2026 06 11 Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by persistent synovitis and synovial hyperplasia. Although interleukin 1 (IL-1) signaling is an important inflammatory pathway in RA, the regulation of IL-1 receptor accessory protein (IL-1RAP) has not been comprehensively characterized. This cross-sectional study evaluated IL-1RAP alterations in RA at the transcriptional and protein levels, including its membrane-bound and soluble forms. Thirty female RA patients were stratified according to disease activity into low, moderate, and high disease activity subgroups, and 15 healthy controls were included. Surface expression of membrane-bound IL-1RAP (mIL-1RAP) was assessed on peripheral blood leukocyte subsets, including CD4+ and CD8+ T cells, B cells, monocytes, and granulocytes. Plasma soluble IL-1RAP (sIL-1RAP) levels were measured, and relative mRNA expression of IL1RAP, IL1A, IL1B, IL1R1, IL1R2, and IL1RN was quantified in peripheral blood mononuclear cells (PBMCs). mIL-1RAP expression was increased in several immune cell subsets, particularly in patients with high disease activity, and was positively associated with disease activity. In contrast, circulating sIL-1RAP levels were reduced and inversely associated with disease activity. IL1RAP, IL1B, and IL1RN transcripts were elevated, with the highest expression in patients with high disease activity. IL1R1 and IL1R2 expression remained unchanged, whereas IL1A upregulation was limited to high disease activity. These findings suggest disease activity–dependent alterations in IL-1RAP–related pathways in RA. IL-1RAP may represent a candidate biomarker of disease activity, but larger longitudinal studies are needed to validate its diagnostic, monitoring, and therapeutic relevance. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4811 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4811/2430