Cohort profile: SCREEN-RA: design, methods and perspectives of a Swiss cohort study of first-degree relatives of patients with rheumatoid arthritis

Abstract

PurposeRheumatoid arthritis (RA) is an insidious autoimmune disease, with an immunological onset years before diagnosis. Early interventions in preclinical stages could prevent or minimise the progression towards irreversible joint damage. The SCREEN-RA cohort (Evaluation of a SCREENing strategy for Rheumatoid Arthritis) aims to characterise the preclinical stages of the disease, to identify environmental risk factors, and to discover or validate novel biomarkers predictive for RA development.ParticipantsSCREEN-RA includes an at-risk population for RA, namely first-degree relatives of patients with established RA.Findings to dateThe cohort started in 2009 is composed of mostly asymptomatic healthy individuals (total n=1458, 7262 person-years), with a mean age of 44 years at enrolment, 74% female and 91% Caucasian ethnicity. During the study period, 16 participants have developed RA. All participants provide baseline serum, DNA and RNA samples, and in a subset, stool samples and oral examination are performed for microbiota assessment. At enrolment, 10% of participants had asymptomatic autoimmunity associated with RA (n=147), 10% presented ‘clinically suspect arthralgias’ (n=143) and 3% reported arthralgias in conjunction with autoimmunity or high genetic risk (n=51). Studies with this cohort have uncovered risk factors for RA development, such as female hormonal factors, poor oral health or intestinal dysbiosis.Future plansFuture directions include immunological and ‘multiomics’ approaches to discover new biological markers of progression towards RA, as well as testing preventive interventions in ‘high-risk’ population.

A Roadmap for Investigating Preclinical Autoimmunity Using Patient-Oriented and Epidemiologic Study Designs: Example of Rheumatoid Arthritis

“…This Swiss study also enrolls first-degree relatives and high-risk individuals for RA risk ( 98 ). This population was featured as these individuals are considered more likely to develop RA due to likely predisposition to genetic factors associated with RA risk ( 98 ).…”

“…This Swiss study also enrolls first-degree relatives and high-risk individuals for RA risk ( 98 ). This population was featured as these individuals are considered more likely to develop RA due to likely predisposition to genetic factors associated with RA risk ( 98 ). The cohort, termed SCREEN-RA or Evaluation of a SCREENing strategy for RA, began in 2009 and followed initially “healthy, asymptomatic individuals” predisposed to developing RA due to familial history ( 98 ).…”

“…This population was featured as these individuals are considered more likely to develop RA due to likely predisposition to genetic factors associated with RA risk ( 98 ). The cohort, termed SCREEN-RA or Evaluation of a SCREENing strategy for RA, began in 2009 and followed initially “healthy, asymptomatic individuals” predisposed to developing RA due to familial history ( 98 ). At baseline, all individuals were undiagnosed with RA, but were at various stages of presentation with some attesting to arthralgias, while others had high autoantibodies without symptoms, and some who only identified as FDRs without additional risk indicators or suggestion of early disease onset ( 98 ).…”

“…The cohort, termed SCREEN-RA or Evaluation of a SCREENing strategy for RA, began in 2009 and followed initially “healthy, asymptomatic individuals” predisposed to developing RA due to familial history ( 98 ). At baseline, all individuals were undiagnosed with RA, but were at various stages of presentation with some attesting to arthralgias, while others had high autoantibodies without symptoms, and some who only identified as FDRs without additional risk indicators or suggestion of early disease onset ( 98 ). With the founding of the study, the team hoped to strategically build a tool, combining various preclinical RA features, that could forecast a likely RA diagnosis within 3-5 years of baseline ( 98 ).…”

“…To address environmental habits and factors, genetics, and autoimmunity, questionnaires, DNA and RNA, and serum samples were collected, respectively ( 98 ). In a subpopulation of more “high risk” FDRs, presenting with 2 copies of the notorious shared epitope, elevated autoimmunity markers at baseline, or undifferentiated arthritis, additional stool samples were collected, and oral exams were performed to assess dental microbiota ( 98 ). After each FDR or high-risk individual was enrolled, follow-up questionnaires, built in tandem with SERA questionnaires to increase reproducibility of results, were mailed annually to monitor incident case development and track environmental and lifestyle conditions ( 98 ).…”