ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1862

Genetic Influences on Occurrence of Axial Spondyloarthritis (axSpA) in First-degree Relatives During a Prospective Study Lasting 35 Years

Muhammad Khan1, Sjef van der Linden2, Peter Villiger3, Zhixiu Li4, Mohammad Khan5, Heinz Baumberger6, Hermine Zandwijk7 and Matthew Brown8, 1Case Western Reserve University, Cleveland OH, Westlake, OH, 2Department of Rheumatology, Immunology and Allergology, University of Bern, Inselspital, Bern, Switzerland, Mortroux, Belgium, 3Department of Rheumatology, Immunology and Allergology, University of Bern, Inselspital, Switzerland, Bern, Switzerland, 4Queensland University of Technology (QUT), Translational Genomics Group, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Qld, Australia, Brisbane, Queensland, Australia, 5Kent State University, Kent, OH, 6Retired, Flims, Tajikistan, 7Retired, Mortroux, Belgium, 8Guy's and St Thomas, NHS Foundation Trust and King's College London NIHR Biomedical Research Centre, King's College London, London, United Kingdom, London, United Kingdom

Meeting: ACR Convergence 2020

Keywords: , , , ,

Session Information

Date: Monday, November 9, 2020

Session Title: Spondyloarthritis Including Psoriatic Arthritis – Diagnosis, Manifestations, & Outcomes Poster III: Axial SpA

Session Type: Poster Session D

Session Time: 9:00AM-11:00AM

Background/Purpose: To investigate the recurrence rate (RR) of ankylosing spondylitis (AS) over a lifespan, probands with clinically diagnosed AS and their first-degree relatives (FDRs) were studied in a Swiss cohort during 35 years of follow-up.

Methods: In 1985 members of the Swiss AS Patient Society who had been diagnosed as having AS by their own physicians, as well as their FDRs, were invited to participate in the current study. After obtaining ethical approval and informed consent, 363 probands and 715 first-degree relatives were recruited to the study.   Participants completed questionnaires on disease manifestations, underwent rheumatological examination of axial and peripheral joints, and were genotyped for HLA-B27. 360 probands and all 713 relatives aged ≥ 18 year underwent pelvic radiography unless pregnant, which were then scored according to the modified New York AS (mNYAS) criteria.  Participants with a clinical diagnosis of AS with or without radiographic evidence of disease were deemed to have ‘axial spondyloarthritis’ (axSpA), those meeting the mNYAS criteria were said to have AS, and those with a clinical diagnosis of AS but not meeting the mNYAS criteria nr-axSpA.  Following further ethics review and approval, a follow-up study was performed in 2019.  A total of 462 surviving consenting original participants completed a 157 item disease related questionnaire, with diagnosis of AS determined by self-report.   RR of axSpA amongst siblings and children of probands were analysed.

Results: The overall RR for FDRs was 41/411 (10%), the parent-child RR being 24/193 (12.4%) and sibling RR 17/218 (7.8%).  Considering FDRs of mNYAS probands, the RR was even higher (41/351, 11.7%), with the parent-child RR being 24/154 (15.6%) and sibling RR 17/197 (8.6%).  Amongst FDRs of probands with nr-axSpA, lower RRs were observed: overall FDR RR was 6/98 (6.1%), parent-child RR 2/39 (5.1%), sibling RR 4/59 (6.8%).  AS occurred in only one HLA-B27(-) relative, with nr-axSpA, and no case of HLA-B27(-) mNYAS was observed amongst FDRs.  Considering HLA-B27(+) FDRs of mNYAS probands, the RR was very high (overall 41/288, 14.2%; mNYAS probands 24/142, 16.9%).  Mother-child RR was substantially higher than father-child RR, particularly amongst children of parents with mNYAS (11/27 vs 13/127 respectively, odds ratio = 6.0, P=3.8×10-4, Fisher’s exact test).  No difference in risk of transmission from affected parents to daughters compared with sons was observed (parent-daughter 15/105 (14.3%), parent-son 9/88 (10.2%), P=0.40), including if the parent was a mother or father.

Conclusion: This study demonstrates that particularly amongst axSpA patients with mNYAS, the RR of axSpA in both siblings and children is very high, particularly amongst HLA-B27 positive relatives (16.9%).   The relatively higher prevalence of mother to child transmission compared to father to child transmission suggests that female AS patients appear to be genetically “enriched” regarding transmission of the disease predisposing genes to their offspring.  This is consistent with polygenic models of AS, in which women with AS require a higher genetic load to develop disease, and are thus more likely to have affected children. 

Disclosure: M. Khan, None; S. van der Linden, None; P. Villiger, None; Z. Li, None; M. Khan, None; H. Baumberger, None; H. Zandwijk, None; M. Brown, None.

To cite this abstract in AMA style:

Khan M, van der Linden S, Villiger P, Li Z, Khan M, Baumberger H, Zandwijk H, Brown M. Genetic Influences on Occurrence of Axial Spondyloarthritis (axSpA) in First-degree Relatives During a Prospective Study Lasting 35 Years [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/genetic-influences-on-occurrence-of-axial-spondyloarthritis-axspa-in-first-degree-relatives-during-a-prospective-study-lasting-35-years/. Accessed April 1, 2023.

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