Searching for New Genetic Biomarkers of Axial Spondyloarthritis

Overview

Journal J Clin Med

Specialty General Medicine

Date 2022 May 28

PMID 35629038

Authors

Bartosz Bugaj

Joanna Wielinska

Katarzyna Bogunia-Kubik

Jerzy Swierkot

Affiliations

Soon will be listed here.

Abstract

Background: Axial spondyloarthritis (axSpA) is a chronic inflammatory condition of the spine. In addition to musculoskeletal symptoms, there are also extra-articular manifestations. The aim of this study was to search for new biomarkers associated with the clinical presentation and treatment response in axSpA patients. Methods: In this study, 106 axSpA patients and 110 healthy controls were enrolled. Six single-nucleotide polymorphisms (SNPs) were selected for genotyping: ERAP1 rs2287987, ERAP2 rs2549782, TNF rs1800629, TNFRSF1A rs767455, TNFRSF1B rs1061622, and FCGR2A rs1801274. Participants were examined at baseline and after 12 and 24 weeks of anti-TNF therapy. Results: SNPs associated with high axSpA initial activity were TNFRSF1A rs767455 and TNFRSF1B rs1061622 (p < 0.008). The ERAP1 rs2287987 AA genotype was more frequently observed in patients with enthesitis (AA vs. G+, p = 0.049), while the TNFRSF1B rs1061622 GG genotype was more common in participants with uveitis (GG vs. TT, p = 0.042). Potential in predicting anti-TNF treatment response was demonstrated by ERAP1 rs2287987, ERAP2 rs2549782, TNFRSF1B rs1061622, and FCGR2A rs1801274. Conclusions: SNPs can be used to identify patients at risk of severe disease to initiate treatment earlier. Genetic testing will allow clinicians to choose the right drug for the patient.

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References

Hu N, Chen X, Wang S, Yuan G, Wang Q, Shu H . The association of polymorphisms in TNF and ankylosing spondylitis in common population: a meta-analysis. Eur Spine J. 2021; 30(6):1402-1410. DOI: 10.1007/s00586-021-06845-w. View

Robinson P, Leo P, Pointon J, Harris J, Cremin K, Bradbury L . The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis. Genes Immun. 2015; 17(1):46-51. DOI: 10.1038/gene.2015.49. View

Cheli S, Pietrantonio F, Clementi E, Falvella F . LightSNiP assay is a good strategy for pharmacogenetics test. Front Pharmacol. 2015; 6:114. PMC: 4451335. DOI: 10.3389/fphar.2015.00114. View

Wielinska J, Swierkot J, Kolossa K, Bugaj B, Chaszczewska-Markowska M, Jeka S . Polymorphisms within Genes Coding for IL-17A and F and Their Receptor as Clinical Hallmarks in Ankylosing Spondylitis. Mediators Inflamm. 2021; 2021:3125922. PMC: 8566063. DOI: 10.1155/2021/3125922. View

Ruyssen-Witrand A, Luxembourger C, Cantagrel A, Nigon D, Claudepierre P, Degboe Y . Association between IL23R and ERAP1 polymorphisms and sacroiliac or spinal MRI inflammation in spondyloarthritis: DESIR cohort data. Arthritis Res Ther. 2019; 21(1):22. PMC: 6332609. DOI: 10.1186/s13075-018-1807-5. View

Garrett S, Jenkinson T, Kennedy L, Whitelock H, Gaisford P, Calin A . A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol. 1994; 21(12):2286-91. View

Pazar B, Safrany E, Gergely P, Szanto S, Szekanecz Z, Poor G . Association of ARTS1 gene polymorphisms with ankylosing spondylitis in the Hungarian population: the rs27044 variant is associated with HLA-B*2705 subtype in Hungarian patients with ankylosing spondylitis. J Rheumatol. 2009; 37(2):379-84. DOI: 10.3899/jrheum.090806. View

Bettencourt B, Rocha F, Alves H, Amorim R, Caetano-Lopes J, Vieira-Sousa E . Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals. Rheumatology (Oxford). 2013; 52(12):2168-76. DOI: 10.1093/rheumatology/ket269. View

Brown M, Li Z, Le Cao K . Biomarker development for axial spondyloarthritis. Nat Rev Rheumatol. 2020; 16(8):448-463. DOI: 10.1038/s41584-020-0450-0. View

10.

Baraliakos X, Kiltz U, Peters S, Appel H, Dybowski F, Igelmann M . Efficiency of treatment with non-steroidal anti-inflammatory drugs according to current recommendations in patients with radiographic and non-radiographic axial spondyloarthritis. Rheumatology (Oxford). 2016; 56(1):95-102. DOI: 10.1093/rheumatology/kew367. View

11.

Kuiper J, van Setten J, Devall M, Cretu-Stancu M, Hiddingh S, Ophoff R . Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis. Hum Mol Genet. 2018; 27(24):4333-4343. PMC: 6276832. DOI: 10.1093/hmg/ddy319. View

12.

Moreno M, Arevalo M, Zamora M, Pontes C, Oliva J, Gratacos J . Comparison of disease activity in patients with ankylosing spondylitis under TNFi or NSAID treatment, is there any difference? An observational study. Reumatol Clin (Engl Ed). 2019; 17(4):192-196. DOI: 10.1016/j.reuma.2019.07.005. View

13.

Reveille J, Sims A, Danoy P, Evans D, Leo P, Pointon J . Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet. 2010; 42(2):123-7. PMC: 3224997. DOI: 10.1038/ng.513. View

14.

Wright G, Kaine J, Deodhar A . Understanding differences between men and women with axial spondyloarthritis. Semin Arthritis Rheum. 2020; 50(4):687-694. DOI: 10.1016/j.semarthrit.2020.05.005. View

15.

Sieper J, Poddubnyy D . What is the optimal target for a T2T approach in axial spondyloarthritis?. Ann Rheum Dis. 2021; 80(11):1367-1369. PMC: 8522449. DOI: 10.1136/annrheumdis-2021-220603. View

16.

Ji Y, Yang X, Yang L, Wu D, Hua F, Lu T . Studies on correlation between single-nucleotide polymorphisms of tumor necrosis factor gene and different stages of ankylosing spondylitis. Cell Biochem Biophys. 2013; 67(3):915-22. DOI: 10.1007/s12013-013-9582-z. View

17.

Londono J, Santos A, Rueda J, Calvo-Paramo E, Burgos-Vargas R, Vargas-Alarcon G . Association of ERAP2 polymorphisms in Colombian HLA-B27+ or HLA-B15+ patients with SpA and its relationship with clinical presentation: axial or peripheral predominance. RMD Open. 2020; 6(2). PMC: 7525252. DOI: 10.1136/rmdopen-2020-001250. View

18.

Marquez Pete N, Maldonado Montoro M, Perez Ramirez C, Martinez Martinez F, Martinez de la Plata J, Daddaoua A . Influence of the rs1801274 and rs396991 Polymorphisms on Response to Abatacept in Patients with Rheumatoid Arthritis. J Pers Med. 2021; 11(6). PMC: 8233911. DOI: 10.3390/jpm11060573. View

19.

Iwaszko M, Wielinska J, Swierkot J, Kolossa K, Sokolik R, Bugaj B . Gene Polymorphisms as Potential Biomarkers of Disease Susceptibility and Response to TNF Inhibitors in Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Patients. Front Immunol. 2021; 12:631603. PMC: 8226138. DOI: 10.3389/fimmu.2021.631603. View

20.

Tsui F, Haroon N, Reveille J, Rahman P, Chiu B, Tsui H . Association of an ERAP1 ERAP2 haplotype with familial ankylosing spondylitis. Ann Rheum Dis. 2009; 69(4):733-6. DOI: 10.1136/ard.2008.103804. View