Progression to Clinical Axial Spondyloarthritis Seen in First-Degree Relatives With HLA-B27 Positivity

Researchers evaluated the presence of imaging features and clinical signs of disease in healthy first-degree relatives of patients with spondyloarthritis.

First-degree relatives (FDRs) of patients with axial spondyloarthritis (axSpA), with human leukocyte antigen (HLA)-B27 positivity, demonstrated progression to clinical disease, according to study results published in Arthritis Care & Research.

Researchers collected data of clinical and imaging features from a multicenter, prospective 5-year cohort Pre-SpA trial. Participants were assessed using the visual analog scale (VAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), VAS total back pain, and VAS nocturnal back pain. At baseline, radiographic imaging of the sacroiliac joints, lumbar spine, and cervical spine, serum inflammatory markers, and HLA-B27 genotyping were recorded.

A total of 151 FDRs were included in the current analysis. At baseline, 98 (65%) FDRs reported back pain, with 19% related to inflammation and 32% related to arthralgia. Serum inflammatory markers were elevated in the cohort, including C-reactive protein (CRP; median interquartile range [IQR], 8.8 mg/L [6.8-12.8 mg/L]; n=24 [16%]) and erythrocyte sedimentation rate (ESR; IQR, 27 mm/hr [24-34 mm/hr]; n=11 [7.3%]).

After 1 year of follow-up, no changes were observed on a group level; however, 6% of FDRs were diagnosed with axSpA, of whom 86% were HLA-B27-positive. There were no statistically differences in demographic, clinical, and imaging findings between HLA-B27-positive and -negative FDRs. Overall, HLA-B27 appeared to be independent of subclinical inflammation and instead associated with progression from subclinical inflammation to overt SpA.

Study limitations included the large population of patients with preexisting back pain (65%). Back pain was identified during the course of the study and many participants had not visited a physician or used pain medication for back pain. Overall, back pain was not a major complaint for participants and may not have been the sole reason for participation in the study. Researchers also noted that they could confirm the validity of the information provided by the FDRs.

“…In seemingly healthy FDRs of patients [with] axSpA, (sub) clinical signs of SpA features are frequently seen with an equal distribution between HLA-B27-positive and -negative FDRs. However, progression towards clinical axSpA is seen mainly in FDRs with HLA-B27-positivity and inflammatory back pain,” the researchers noted.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a list of full disclosures.


De Johng MHY, de Winter JJH, van der Horst-Bruinsma IE, et al. Progression from subclinical inflammation to overt SpA in first degree relatives of SpA patients is associated with HLA-B27: the Pre-SpA cohort. Arthritis Care Res (Hoboken). Published online July 5, 2021. doi:10.1002/acr.24743