Genetic, Environmental, and Serologic Risk Factors for Inflammatory Joint Signs Among First-Degree Relatives without Rheumatoid Arthritis in a Prospective Cohort

Jeffrey A. Sparks¹, Shun-Chiao Chang², Kevin D. Deane³, Ryan W. Gan⁴, Kristen Demoruelle³, Marie L. Feser³, LauraKay Moss³, Jane H. Buckner⁵, Richard M. Keating⁶, Karen H. Costenbader⁷, Peter K. Gregersen⁸, Michael H. Weisman⁹, Ted R. Mikuls¹⁰, James R. O'Dell¹⁰, V. Michael Holers³, Jill M. Norris⁴ and Elizabeth W. Karlson², ¹Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, ²Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, ³Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO, ⁴Epidemiology, Colorado School of Public Health, Aurora, CO, ⁵Benaroya Research Institute at Virginia Mason, Seattle, WA, ⁶Division of Rheumatology, Scripps Health, La Jolla, CA, ⁷Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, ⁸Feinstein Insititute for Medical Research, Manhasset, NY, ⁹Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, ¹⁰Veteran Affairs Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, NE

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: autoantibodies, Environmental factors, genetics, pathogenesis and serologic tests, rheumatoid arthritis

Session Information

Date: Monday, November 9, 2015

Title: Epidemiology and Public Health Poster II: Pathogenesis and Treatment of Systemic Inflammatory Diseases

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Family history of RA in a
first-degree relative increases RA risk 4-fold. Determining risk factors for
inflammatory joint signs (IJS) in this high risk population may elucidate the transition
from genetic susceptibility to inflammatory arthritis in
pre-clinical RA. We examined whether genetic, environmental, and serologic RA factors
were associated with IJS among relatives without RA.

Methods: We evaluated RA factors and IJS in a
prospective cohort of first-degree relatives in the Studies of the Etiology of
RA (SERA). At enrollment, subjects in SERA did not have RA according to the
1987 ACR criteria by clinical exam. Genetic RA risk factors, including 5 HLA-DRB1
(*04 or *01) shared epitope alleles and 45 risk alleles validated
among Caucasian populations, were combined into a weighted genetic risk score (GRS50).
Smoking, BMI, education, parity, CCP, and RF were assessed at baseline. Physical
examination at baseline (n=966) and 2-year follow-up (n=396) assessed IJS as tender
or swollen joints at sites typical for RA (Table). We evaluated the association
of RA factors with IJS at baseline and follow-up using logistic regression, adjusting
for confounders and tested for effect modification.

Results: We analyzed 966 non-Hispanic Caucasian
subjects at baseline. In addition, incident IJS at 2-year follow-up was
analyzed in 262 subjects after excluding 134 with IJS at baseline. At baseline,
mean age was 47.2 years (SD 15.5), 71% were female, 55% were shared epitope-positive,
18% smoked >10 pack-years, and 8% were CCP/RF positive. Smoking >10
pack-years was associated with IJS at baseline (OR 1.59, 95% CI 1.09-2.32) and
incident IJS at 2 years (OR 2.66, 95% CI 1.01-7.03). Current (OR 2.12, 95% CI
1.33-3.38) and past smokers (OR 1.61, 95% CI 1.12-2.33) had significantly higher
odds of baseline IJS. BMI, education, sex/parity, GRS50, and RF/CCP were not
associated with IJS at baseline or follow-up. Among those aged <50 years,
subjects who smoked >10 pack-years had 4-fold increased odds of IJS (OR
4.39, 95% CI 2.22-8.66, Figure) compared to never smokers (p,
interaction 0.02).

Conclusion: In a high-risk cohort of first-degree
relatives without RA, smoking was associated with both prevalent and incident inflammatory
joint signs at sites typical for RA. Those <50 years old who smoked >10
pack-years had the highest risk of IJS with a significant interaction between
smoking and age. Neither genetic nor serologic RA factors were significantly associated
with IJS in this sample. These results suggest that smoking plays a role in inflammatory
arthritis development. Longitudinal studies are needed to further investigate
transitions of pre-clinical RA phases.

Disclosure: J. A. Sparks, None; S. C. Chang, None; K. D. Deane, None; R. W. Gan, None; K. Demoruelle, None; M. L. Feser, None; L. Moss, None; J. H. Buckner, None; R. M. Keating, None; K. H. Costenbader, Arthritis Care and Research, 5,International Journal of Clinical Practice, 5; P. K. Gregersen, Illumina Inc., 1,Janssen Pharmaceutica Product, L.P., 5,Biogen, Idec, 5; M. H. Weisman, None; T. R. Mikuls, None; J. R. O'Dell, None; V. M. Holers, Shared patent with Stanford University for use of biomarkers to predict clinical phenotypes in rheumatoid arthritis., 7; J. M. Norris, None; E. W. Karlson, None.

To cite this abstract in AMA style:

Sparks JA, Chang SC, Deane KD, Gan RW, Demoruelle K, Feser ML, Moss L, Buckner JH, Keating RM, Costenbader KH, Gregersen PK, Weisman MH, Mikuls TR, O'Dell JR, Holers VM, Norris JM, Karlson EW. Genetic, Environmental, and Serologic Risk Factors for Inflammatory Joint Signs Among First-Degree Relatives without Rheumatoid Arthritis in a Prospective Cohort [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/genetic-environmental-and-serologic-risk-factors-for-inflammatory-joint-signs-among-first-degree-relatives-without-rheumatoid-arthritis-in-a-prospective-cohort/. Accessed .

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