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. 2022 May;8(1):e002302.
doi: 10.1136/rmdopen-2022-002302.

Heterogeneity of axial spondyloarthritis: genetics, sex and structural damage matter

Zhixiu Li  1   2 , Sjef M van der Linden  3   4 , Muhammad Asim Khan  5 , Heinz Baumberger  6 , Hermine van Zandwijk  7 , Mohammad Kazim Khan  8 , Peter M Villiger  9   10 , Matthew A Brown  11   12
Affiliations

Heterogeneity of axial spondyloarthritis: genetics, sex and structural damage matter

Zhixiu Li et al. RMD Open. 2022 May.

Abstract

Objective: Axial spondyloarthritis (axSpA) comprises both radiographic and non-radiographic disease. However, the paucity of specific objective measures for the disease and current classification criteria showing suboptimal specificity contribute to disease heterogeneity observed in clinical practice and research. We used a historical cohort of patients with axSpA to assess sources of heterogeneity.

Methods: The study involved 363 axSpA probands recruited from membership of the Swiss Ankylosing Spondylitis Patient Society. Participants underwent examination by a rheumatologist, completed questionnaires and provided blood samples for HLA typing. Patients underwent radiography of sacroiliac joints and were categorised according to the New York (NY) criteria (ankylosing spondylitis (AS) or non-radiographic axSpA (nr-axSpA)) and HLA-B27 status. Genetic characterisation by single nucleotide polymorphism microarray was performed and AS polygenic risk scores (PRS) were calculated.

Results: Considerable heterogeneity was observed. The male to female ratio for AS (NY+) was 3:1, but 1:1 for nr-axSpA. For HLA-27(+) AS, the ratio was 2.5:1, but nearly 1:1 for HLA-B27(-) disease. Women with nr-axSpA had strikingly lower mean PRS and lower HLA-B27 prevalence than men with nr-axSpA or NY(+) male and female patients with AS. PRS was able to distinguish male but not female patients with nr-axSpA from related healthy first-degree relatives. Radiographic sacroiliitis was strongly associated with HLA-B27, especially in men.

Conclusion: Women clinically diagnosed with axSpA but without radiographic sacroiliitis as a group have a disease that is distinct from AS by the modified New York criteria overall and from nr-axSpA in men. Given the high degree of heterogeneity, stratified or adjusted analysis of effectiveness studies is indicated, taking genetics, sex and radiographic damage (sacroiliitis) into account.

Keywords: Ankylosing Spondylitis; Epidemiology; Polymorphism, Genetic.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Flow chart of 363 probands with axial spondyloarthritis by radiographic status, gender and HLA-B27 prevalence. The radiographic status is unknown for three probands.
Figure 2
Figure 2
The figure shows that a higher proportion of patients with AS, defined by the radiographic New York criteria for sacroiliitis, are men. For nr-axSpA the ratio is about equal. Among women with nr-axSpA the prevalence of HLA-B27(−) disease is considerably higher compared with men and women with AS (by the New York criteria) and men with nr-axSpA. AS, ankylosing spondylitis; nr-axSpA, non-radiographic axial spondyloarthritis; SpA, spondyloarthritis.
Figure 3
Figure 3
(A) Discriminatory performance of PRS among probands with AS and nr-axSpA compared with HC. (B) Discriminatory performance of PRS among female and male probands with AS and nr-axSpA compared with HC. AS, ankylosing spondylitis; AUC, area under the curve; HC, healthy unrelated control; nr-axSpA, non-radiographic axial spondyloarthritis; PRS, polygenic risk score.
Figure 4
Figure 4
(A) Discriminatory performance of PRS among probands with AS and nr-axSpA compared with related healthy controls (FDR). (B) Discriminatory performance of PRS among female and male probands with AS and nr-axSpA compared with related healthy controls (FDR). AS, ankylosing spondylitis; AUC, area under the curve; FDR, first-degree relative; HC, healthy unrelated control; nr-axSpA, non-radiographic axial spondyloarthritis; PRS, polygenic risk score.
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References

    1. de Blecourt J, Polman A, de BlecourtBLECOURT-MeindersmaMEINDERSMA T . Hereditary factors in rheumatoid arthritis and ankylosing spondylitis. Ann Rheum Dis 1961;20:215–23. 10.1136/ard.20.3.215 - DOI - PMC - PubMed
    1. Bakland G, Nossent HC, Gran JT. Incidence and prevalence of ankylosing spondylitis in northern Norway. Arthritis Rheum 2005;53:850–5. 10.1002/art.21577 - DOI - PubMed
    1. De Angelis R, Salaffi F, Grassi W. Prevalence of spondyloarthropathies in an Italian population sample: a regional community-based study. Scand J Rheumatol 2007;36:14–21. 10.1080/03009740600904243 - DOI - PubMed
    1. Exarchou S, Lindström U, Askling J, et al. . The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations: a nationwide register study. Arthritis Res Ther 2015;17:118. 10.1186/s13075-015-0627-0 - DOI - PMC - PubMed
    1. Haglund E, Bremander AB, Petersson IF, et al. . Prevalence of spondyloarthritis and its subtypes in southern Sweden. Ann Rheum Dis 2011;70:943–8. 10.1136/ard.2010.141598 - DOI - PubMed

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