Clinical and Imaging Signs of Spondyloarthritis in First-Degree Relatives of HLA-B27-Positive Ankylosing Spondylitis Patients: The Pre-Spondyloarthritis (Pre-SpA) Cohort Study

Arthritis Rheumatol. 2016 Oct;68(10):2444-55. doi: 10.1002/art.39766.


Objective: To investigate whether seemingly healthy first-degree relatives of patients with ankylosing spondylitis (AS) have clinical, laboratory, or imaging features of spondyloarthritis (SpA).

Methods: First-degree relatives (ages 18-40 years) of HLA-B27-positive AS patients were included in the pre-spondyloarthritis (Pre-SpA) cohort, a prospective inception cohort study. Clinical, biologic, and imaging features were recorded. First-degree relatives were classified according to several sets of SpA classification criteria.

Results: We report baseline features of 51 first-degree relatives included in this study. Twenty-nine (57%) had back pain, 2 (4%) had psoriasis, 1 (2%) had inflammatory bowel disease, and 1 (2%) had uveitis. Three (6%) had low-grade sacroiliitis, 1 (2%) had cervical syndesmophytes on radiography, and 10 (20%) had bone marrow edema on magnetic resonance imaging of the sacroiliiac joints. Seventeen of 51 first-degree relatives (33%) fulfilled SpA classification criteria: 7 (14%) fulfilled both Assessment of SpondyloArthritis international Society (ASAS) axial SpA and European Spondylarthropathy Study Group (ESSG) classification criteria, 6 (12%) fulfilled only ASAS axial SpA classification criteria, and 4 (8%) fulfilled only ESSG classification criteria; 3 (6%) also fulfilled the Amor criteria. None fulfilled other SpA classification criteria. First-degree relatives fulfilling the ASAS axial SpA and/or ESSG classification criteria had more frequent inflammatory back pain, had a higher level of disease activity, and had more psoriasis. No differences were found in parameters of inflammation, peripheral and extraarticular disease other than psoriasis, and HLA-B27 positivity between those who did and those who did not fulfill the ASAS axial SpA and/or ESSG classification criteria. Four first-degree relatives (12%) who did not fulfill the ASAS axial SpA and/or ESSG classification criteria had imaging abnormalities suggestive of SpA.

Conclusion: A substantial proportion of seemingly healthy first-degree relatives of HLA-B27-positive AS patients have clinical and/or imaging abnormalities suggestive of SpA. Thirty-three percent could be classified as having SpA. Further follow-up will show which first-degree relatives will develop clinically manifest SpA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Back Pain / epidemiology*
  • Bone Marrow Diseases / diagnostic imaging
  • Bone Marrow Diseases / epidemiology
  • Cohort Studies
  • Edema / diagnostic imaging
  • Edema / epidemiology
  • Family*
  • Female
  • HLA-B27 Antigen / genetics
  • Humans
  • Inflammatory Bowel Diseases / epidemiology*
  • Magnetic Resonance Imaging
  • Male
  • Osteophyte / diagnostic imaging
  • Osteophyte / epidemiology
  • Prospective Studies
  • Psoriasis / epidemiology*
  • Radiography
  • Sacroiliitis / diagnostic imaging
  • Sacroiliitis / epidemiology*
  • Spondylarthropathies / diagnostic imaging*
  • Spondylarthropathies / physiopathology
  • Spondylitis, Ankylosing* / genetics
  • Uveitis / epidemiology*
  • Young Adult


  • HLA-B27 Antigen