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A prospective study of the development of inflammatory arthritis in the family members of Indigenous North American people with rheumatoid arthritis

Author

Tanner S1, Dufault B2, Smolik I1, Meng X1, Anaparti V1, Hitchon C1, Robinson DB1, William R3, Sokolove J3, Lahey L3, Ferucci ED4, El-Gabalawy H1. Arthritis Rheumatol. 2019 Mar 12. doi: 10.1002/art.40880. [Epub ahead of print]

Author Information

1 Arthritis Center, Department of Rheumatology, University of Manitoba, Winnipeg, MB, Canada.

2 George and Fay Yee Centre for Healthcare Innovation, Department of Community Health Sciences, University of Manitoba, Canada.

3 Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA.

4 Alaska Native Tribal Health Consortium, Anchorage, AK.

Abstract

OBJECTIVE: 

We prospectively followed a cohort of unaffected relatives of Indigenous North American (INA) people with RA to define the incidence of inflammatory arthritis (IA) and autoantibody prevalence in this population.

METHODS: 

Unaffected relatives of INA people with RA from central Canada and Alaska were followed systematically from 2005 until 2017. Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) were tested at every visit and a subset was tested for ACPA fine specificity using a custom multiplex assay. Multi-state models based on all available study visits were developed to determine the likelihood of transitioning between autoantibody states, or to IA.

RESULTS: 

18/374 (4.8%) relatives developed seropositive IA after 4.7 (±2.4) years of follow-up, giving a transition rate of 9.2 cases per 1000 person-years. Thirty percent of those who developed IA were seronegative at baseline but all were seropositive at IA onset. Although 30% of ACPA/RF double seropositive individuals developed IA after 3.9 (±2.6) years, the majority did not develop IA. Multi-state modeling indicated a 71% and 68% likelihood of ACPA and RF seropositive states, respectively, reverting to seronegativity after five years, and a 39% likelihood of ACPA/RF double seropositive state becoming seronegative. Fine specificity testing demonstrated expansion of the ACPA repertoire prior to development of IA.

CONCLUSION: 

Despite a high incidence of IA in this cohort of at-risk relatives of INA people with RA, a large proportion of autoantibody positive individuals do not develop IA and revert back to an autoantibody negative state.