Identifying Novel Risk HLA Allotypes in Different Spondyloarthritis Subtypes

MRI sacroiliac articulation, ankylosing spondyloarthritis
Researchers studied the HLA profile of patients with enthesitis and/or arthritis not fulfilling the ASAS criteria, with an emphasis on psoriatic arthritis and undifferentiated spondyloarthritis.

Novel risk human leukocyte antigen (HLA) allotypes for different subgroups of spondyloarthritis (SpA) were identified in an Italian population, according to findings from a study published in Journal of Clinical Medicine.

Researchers sought to examine the association between the HLA class I and class II haplotypes and susceptibility to enthesitis and/or arthritis (E/A), with a focus on patients with E/A with a response to treatment with disease-modifying antirheumatic drugs (DMARDs) but not meeting the Assessment of SpondyloArthritis International Society (ASAS) classification criteria (E/A ASAS-), compared with E/A ASAS+ forms of disease, including psoriatic arthritis (PsA) and undifferentiated SpA (uSpA).

Patients with symptomatic peripheral E/A, which was confirmed by ultrasound, were enrolled in the current retrospective study from the Rheumatology Research Program Unit at the University of Bari, Italy.

Between 2008 and 2013, a total of 113 consecutive patients with symptomatic peripheral E/A and 318 HLA-I and HLA-II serotyped healthy donors as control participants were included. Of the 113 patients with E/A, 73 were ASAS+ (54 with PsA and 19 with uSpA) and 40 were ASAS-, responsive to conventional DMARDs. In the whole E/A group, the female-to-male ratio was 4:1. Mean patient age was 53.8±11.4 years; mean age at symptom onset was 44.5 ±12.7 years. In the control group, the female-to-male ratio was 1:1, with a mean age of 34.82±12.21 years.

Responses to the item “family history of psoriasis” were statistically higher in the PsA than in the uSpA (P <.001) and ASAS- (P <.001) subgroups. Further, significant differences in age at onset of symptoms were shown between PsA and ASAS- (P =.001), which was higher in the ASAS- group. In addition, the HLA-B27 distribution percentage in the whole E/A group (P =.001), as well as the PsA subgroup (P =.001) and the uSpA subgroup (P <.001), was statistically significantly higher than in the control group.

In the whole E/A group, significant independent associations with HLA-A28(68), B27, Cw3, Cw12, and DQ1 were reported. On an individual basis, PsA was linked to HLA-B27 and DQ1; uSpA was linked to HLA-B16(38.39) and B27; and E/A ASAS- was linked to HLA-A28(68), Cw8, and Cw12.

Researchers concluded that HLA typing could help diagnose and treat E/A subgroups, and identify family members who might be at risk, particularly individuals with enthesitis and/or arthritis who do not meet the criteria for being diagnosed with uSpA. However, confirmation of these findings in large, multicenter cohort studies is warranted.


Favoino E, Urso L, Serafino A, et al. HLA allele prevalence in disease-modifying antirheumatic drugs-responsive enthesitis and/or arthritis not fulfilling ASAS criteria: comparison with psoriatic and undifferentiated spondyloarthritis. J Clin Med. 2021;10(14):3006. doi:10.3390/jcm10143006