Agata N Burska1, Jessica Neilan1, Ruth E Chisman2, Rujiraporn Pitaksalee3, Richard Hodgett4, Helena Marzo-Ortega1, Philip G Conaghan1, Robert West5, Paul Emery1, Frederique Ponchel6. 1. Leeds Institute of Rheumatic and Musculoskeletal Medicine and NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, and the Leeds Trust Teaching Hospital, Chapel Allerton Hospital, Leeds, UK. 2. Transplant Immunology Laboratory, St James' University Hospital, Leeds, UK. 3. Leeds Institute of Rheumatic and Musculoskeletal Medicine and NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, and the Leeds Trust Teaching Hospital; Leeds University Business School, University of Leeds, UK. 4. Leeds University Business School, University of Leeds, UK. 5. Leeds Institute of Health Sciences, University of Leeds, UK . 6. Leeds Institute of Rheumatic and Musculoskeletal Medicine and NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, and the Leeds Trust Teaching Hospital, Chapel Allerton Hospital, Leeds, UK. f.ponchel@leeds.ac.uk.
Abstract
OBJECTIVES: Despite the well-established value of currently used classification criteria for the early diagnosis of rheumatoid arthritis (RA) there is a constant demand for novel biomarkers notably in autoantibody-negative patients. Interleukin 7 (IL-7) has been reported as a candidate diagnostic biomarker based on ACR-1987 criteria. However, clinical practice has moved to using the EULAR 2010 classification criteria. Therefore, to advance the use of IL-7 alongside the RA biomarker pipeline, we repeated the original study in a new cohort. METHODS: 255 patients were recruited. IL-7 was quantified by ELISA. Univariate and regression analyses were used to model RA diagnosis. RESULTS: 123 patients were diagnosed with RA (EULAR 2010) while 132 were classified as non-RA. In univariate analysis, RA was associated with autoantibodies and SE-positivity, higher joint counts, DAS28 (all p<0.001) and CRP (p=0.024). IL-7 was lower in RA (p=0.05). Logistic regression analysis in 227 patients with complete data set confirmed IL-7 was the second best predictive marker (p=0.035) following SJC (p=0.007) with good model fit (AUROC=0.889). A second model investigated 147 ACPA-negative patients: lower IL7 was the second best predictive marker (p=0.075) behind SJC (p=0.013). CONCLUSIONS: This study validates our previous results from a UK cohort using EULAR 2010 criteria although the predictive power associated with IL-7 is lower than in the study using ACR 1987 criteria (both French/UK cohorts). IL-7 remains a potential biomarker for ACPA-negative RA although further validation with larger numbers of ACPA-negative patients is still needed notably to translate these results into clinical applicability.
OBJECTIVES: Despite the well-established value of currently used classification criteria for the early diagnosis of rheumatoid arthritis (RA) there is a constant demand for novel biomarkers notably in autoantibody-negative patients. Interleukin 7 (IL-7) has been reported as a candidate diagnostic biomarker based on ACR-1987 criteria. However, clinical practice has moved to using the EULAR 2010 classification criteria. Therefore, to advance the use of IL-7 alongside the RA biomarker pipeline, we repeated the original study in a new cohort. METHODS: 255 patients were recruited. IL-7 was quantified by ELISA. Univariate and regression analyses were used to model RA diagnosis. RESULTS: 123 patients were diagnosed with RA (EULAR 2010) while 132 were classified as non-RA. In univariate analysis, RA was associated with autoantibodies and SE-positivity, higher joint counts, DAS28 (all p<0.001) and CRP (p=0.024). IL-7 was lower in RA (p=0.05). Logistic regression analysis in 227 patients with complete data set confirmed IL-7 was the second best predictive marker (p=0.035) following SJC (p=0.007) with good model fit (AUROC=0.889). A second model investigated 147 ACPA-negative patients: lower IL7 was the second best predictive marker (p=0.075) behind SJC (p=0.013). CONCLUSIONS: This study validates our previous results from a UK cohort using EULAR 2010 criteria although the predictive power associated with IL-7 is lower than in the study using ACR 1987 criteria (both French/UK cohorts). IL-7 remains a potential biomarker for ACPA-negative RA although further validation with larger numbers of ACPA-negative patients is still needed notably to translate these results into clinical applicability.