To Be or Not to B27 Positive: Implications for the Phenotypes of Axial Spondyloarthritis Outcomes. Data from a Large Multiracial Cohort from the Brazilian Registry of Spondyloarthritis

Background: There is a remarkable variability in the frequency of HLA-B27 positivity in patients with spondyloarthritis (SpA), which may be associated with different clinical presentations worldwide. However, there is a lack of data considering ethnicity and sex on the evaluation of the main clinical and prognostic outcomes in mixed-race populations. The aim of this study was to evaluate the frequency of HLA-B27 and its correlation with disease parameters in a large population of patients from the Brazilian Registry of Spondyloarthritis (RBE).

Methods: The RBE is a multicenter, observational, prospective cohort that enrolled patients with SpA from 46 centers representing all five geographic regions of Brazil. The inclusion criteria were as follow: (1) diagnosis of axSpA by an expert rheumatologist; (2) age ≥18 years; (3) classification according to ASAS axial. The following data were collected via a standardized protocol: demographic data, disease parameters and treatment historical.

Results: A total of 1096 patients were included, with 73.4% HLA-B27 positivity and a mean age of 44.4 (±13.2) years. Positive HLA-B27 was significantly associated with male sex, earlier age at disease onset and diagnosis, uveitis, and family history of SpA. Conversely, negative HLA-B27 was associated with psoriasis, higher peripheral involvement and disease activity, worse quality of life and mobility.

Conclusions: Our data showed that HLA-B27 positivity was associated with a classic axSpA pattern quite similar to that of Caucasian axSpA patients around the world. Furthermore, its absence was associated with peripheral manifestations and worse outcomes, suggesting a relevant phenotypic difference in a highly miscegenated population.

References

BREWERTON D, Hart F, Nicholls A, Caffrey M, James D, Sturrock R . Ankylosing spondylitis and HL-A 27. Lancet. 1973; 1(7809):904-7. DOI: 10.1016/s0140-6736(73)91360-3. View

Schlosstein L, Terasaki P, Bluestone R, Pearson C . High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med. 1973; 288(14):704-6. DOI: 10.1056/NEJM197304052881403. View

Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J . The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009; 68(6):777-83. DOI: 10.1136/ard.2009.108233. View

Stolwijk C, Boonen A, van Tubergen A, Reveille J . Epidemiology of spondyloarthritis. Rheum Dis Clin North Am. 2012; 38(3):441-76. PMC: 4470267. DOI: 10.1016/j.rdc.2012.09.003. View

Fahed H, Mauro D, Ciccia F, Ziade N . What Does Human Leukocyte Antigen B27 Have to Do with Spondyloarthritis?. Rheum Dis Clin North Am. 2020; 46(2):225-239. DOI: 10.1016/j.rdc.2020.01.002. View

Bittar M, Yong W, Magrey M, Khan M . Worldwide Differences in Clinical Phenotype of Axial Spondyloarthritis. Curr Rheumatol Rep. 2021; 23(10):76. DOI: 10.1007/s11926-021-01043-5. View

Ziade N . Human leucocyte antigen-B27 testing in clinical practice: a global perspective. Curr Opin Rheumatol. 2023; 35(4):235-242. DOI: 10.1097/BOR.0000000000000946. View

Coates L, Baraliakos X, Blanco F, Blanco-Morales E, Braun J, Chandran V . The Phenotype of Axial Spondyloarthritis: Is It Dependent on HLA-B27 Status?. Arthritis Care Res (Hoboken). 2020; 73(6):856-860. DOI: 10.1002/acr.24174. View

Arevalo Salaet M, Lopez-Medina C, Moreno M, Navarro-Compan V, Fontova J, Llop M . Association between HLA-B27 and peripheral spondyloarthritis phenotype: results from the ASAS perSpA study. RMD Open. 2023; 8(2). PMC: 9743377. DOI: 10.1136/rmdopen-2022-002696. View

10.

Frohlich F, Micheroli R, Hebeisen M, Kissling S, Burki K, Exer P . HLA-B27 as a predictor of effectiveness of treatment with TNF inhibitors in axial spondyloarthritis: data from the Swiss Clinical Quality Management Registry. Clin Rheumatol. 2022; 42(5):1267-1274. PMC: 10102047. DOI: 10.1007/s10067-022-06490-8. View

11.

de Jong H, de Winter J, van der Horst-Bruinsma I, van Schaardenburg D, van Gaalen F, van Tubergen A . Progression From Subclinical Inflammation to Overt Spondyloarthritis in First-Degree Relatives of Patients in Association With HLA-B27: The Pre-Spondyloarthritis Cohort. Arthritis Care Res (Hoboken). 2021; 74(12):2076-2084. PMC: 10087210. DOI: 10.1002/acr.24743. View

12.

van der Linden S, Khan M, Li Z, Baumberger H, van Zandwijk H, Khan M . Recurrence of axial spondyloarthritis among first-degree relatives in a prospective 35-year-follow-up family study. RMD Open. 2022; 8(2). PMC: 9315900. DOI: 10.1136/rmdopen-2022-002208. View

13.

Li Z, Khan M, van der Linden S, Winkens B, Villiger P, Baumberger H . HLA-B27, axial spondyloarthritis and survival. Ann Rheum Dis. 2023; 82(12):1558-1567. DOI: 10.1136/ard-2023-224434. View

14.

Chimenti M, Alten R, DAgostino M, Gremese E, Kiltz U, Lubrano E . Sex-associated and gender-associated differences in the diagnosis and management of axial spondyloarthritis: addressing the unmet needs of female patients. RMD Open. 2021; 7(3). PMC: 8655606. DOI: 10.1136/rmdopen-2021-001681. View

15.

Li Z, van der Linden S, Khan M, Baumberger H, van Zandwijk H, Khan M . Heterogeneity of axial spondyloarthritis: genetics, sex and structural damage matter. RMD Open. 2022; 8(1). PMC: 9083385. DOI: 10.1136/rmdopen-2022-002302. View

16.

Ensslin C, Micheroli R, Kissling S, Gotschi A, Burki K, Bram R . Impact of sex on spinal radiographic progression in axial spondyloarthritis: a longitudinal Swiss cohort analysis over a period of 10 years. RMD Open. 2023; 9(3). PMC: 10387740. DOI: 10.1136/rmdopen-2023-003340. View

17.

Saad C, Goncalves C, Sampaio-Barros P . Seronegative arthritis in Latin America: a current review. Curr Rheumatol Rep. 2014; 16(9):438. DOI: 10.1007/s11926-014-0438-3. View

18.

Khan M, Braun W, Kushner I, Grecek D, Muir W, Steinberg A . HLA B27 in ankylosing spondylitis: differences in frequency and relative risk in American Blacks and Caucasians. J Rheumatol Suppl. 1977; 3:39-43. View

19.

Reveille J, Weisman M . The epidemiology of back pain, axial spondyloarthritis and HLA-B27 in the United States. Am J Med Sci. 2013; 345(6):431-6. PMC: 4122314. DOI: 10.1097/maj.0b013e318294457f. View

20.

Resende G, Saad C, de Oliveira D, de Sousa Bueno Filho J, Sampaio-Barros P, Pinheiro M . HLA-B27 positivity in a large miscegenated population of 5,389,143 healthy blood marrow donors in Brazil. Adv Rheumatol. 2023; 63(1):16. DOI: 10.1186/s42358-023-00302-6. View