Aryl hydrocarbon receptor gene expression in ankylosing spondylitis and its correlation with interleukin-17, RAR-related orphan receptor gamma t expression, and disease activity indices

Maryam Ahmadi1*, Narjes Soleimanifar2*, Abdolrahman Rostamian3, Maryam Sadr2, Hanieh Mojtahedi2, Abeda Mazari1, Mohammad Hossein Nicknam1,2, Sara Assadiasl2

1Department of Immunology, School of Medicine, Tehran University of Medical Science, Tehran, Iran
2Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran
3Department of Rheumatology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran

Keywords: Ankylosing spondylitis, aryl hydrocarbon receptor, interlukin-17, T helper 17.

Abstract

Objectives: Considering the role of T helper (Th)17 cells in the pathogenesis of ankylosing spondylitis (AS), the aim of this study was to determine the correlation between aryl hydrocarbon receptor (AHR) gene expression and the expression of Th17-related genes including interleukin (IL)-17 and RAR-related orphan receptor gamma t (RORγt) transcription factor.

Patients and methods: Thirty patients with AS (26 males, 4 females; mean age: 36.1±8.1 years) and 30 age- and sex-matched healthy individuals (26 males, 4 females; mean age: 36.2±14.6 years) were recruited for the case-control study between June 2021 and January 2022. Ribonucleic acid (RNA) was extracted from peripheral blood cells and expression levels of AHR, IL-17, RORγt, and AHR repressor (AHRR) genes were evaluated using real-time polymerase chain reaction technique. The serum level of IL-17 was evaluated with enzyme-linked immunosorbent assay.

Results: The results showed a nonsignificant elevation of AHR, IL-17, and RORγt gene expression in the patient group compared to the control. There was a direct correlation between AHR gene expression and IL-17 and RORγt genes and a negative correlation between AHR and AHRR expression. Moreover, AHR gene expression showed a weak correlation with disease activity indices, including Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Global Score, and Ankylosing Spondylitis Quality of Life. Moreover, the serum level of IL-17 was higher in AS patients compared to the healthy group (p=0.02).

Conclusion: Upregulated expression of the AHR gene in ankylosing spondylitis and its correlation with IL-17 and ROR-γ t gene expression suggests that it could be a potential diagnostic and therapeutic target for AS.

* The first two authors contributed equally to this manuscript.

Citation: Ahmadi M, Soleimanifar N, Rostamian A, Sadr M, Mojtahedi H, Mazari A, et al. Aryl hydrocarbon receptor gene expression in ankylosing spondylitis and its correlation with interleukin-17, RAR-related orphan receptor gamma t expression, and disease activity indices. Arch Rheumatol 2024;39(1):123-132.doi: 10.46497/ ArchRheumatol.2023.10203.

Ethics Committee Approval

The study protocol was approved by the Tehran University of Medical Sciences Ethics Committee (date: 20.03.2022, no: IR.TUMS. CHMC.REC.1400.316). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Data collection and processing: M.A.; Idea, concept, design, and literature review: N.S.; Design and data collection: A.R.; Materials and processing: M.S.; Analysis and interpretation: H.M.; Data collection: A.M.; References, funding and critical review: M.H.N.; Writing the article, control/supervision: S.A.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This study was supported financially by the Tehran University of Medical Sciences (Grant number: 1400-3-154-56106.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.