Ultrasensitive quantification of serum IL-5 in systemic lupus erythematosus does not reveal utility as a biomarker for disease activity or damage

Abstract

Background Interleukin-5 (IL-5) is the principal regulator of eosinophil biology and a key mediator of type 2 immune responses. Despite its recognized role in autoimmunity, its contribution to the pathophysiology of systemic lupus erythematosus (SLE) remains poorly defined, and no previous study has quantified IL-5 using ultrasensitive methodology in this setting. The present study aimed to measure serum IL-5 levels by ultrasensitive assay in a large, well-characterized cohort of SLE patients and to assess its relationship with a broad range of disease manifestations. Methods A comprehensive characterization of 313 patients with SLE was performed, including autoantibody profiles and indices of disease activity (SLE-DAS, SLEDAI-2K, and LLDAS), damage (SLICC-DI), and remission (DORIS). Full hematological profiles were also assessed. IL-5 serum levels were measured using Simoa (Single Molecule Array) technique. A multivariable linear regression analysis was performed to examine the associations between the disease characteristics and circulating IL-5 as the dependent variable. Results In 22 patients with SLE (7%), IL-5 levels were undetectable despite the use of an ultrasensitive assay. Therefore, the relationship between IL-5 and disease-related features was first analyzed after imputing these values, followed by a sensitivity analysis restricted to patients with detectable IL-5 levels. Overall, associations between IL-5 and most disease characteristics, including disease activity, damage, remission/low disease activity states, complement levels, and interferon-related biomarkers, were weak or inconsistent across analyses. Anti-extractable nuclear antigen antibody positivity showed a significant positive association with IL-5 in both the primary and sensitivity analyses. Likewise, no hematological cell line showed a consistent association with IL-5 across both analytical approaches. Conclusion Serum IL-5, as measured by ultrasensitive methodology, does not appear to be a robust biomarker of global disease activity, organ damage, remission status, or hematologic involvement in SLE. Accordingly, our findings do not support the clinical investigation of therapeutic IL-5 blockade in this disease.