Adrian Y. S. Lee^1,2, Ming Wei Lin^1,2, Dan Suan¹, Dimitra Beroukas³, Tom P. Gordon³, Jing Jing Wang³

¹Department of Immunology, Westmead Hospital, Westmead, NSW
²Westmead Institute for Medical Research, University of Sydney, Westmead, NSW
³Department of Immunology, SA Pathology & Flinders University, Bedford Park, SA

 

 

Introduction: Anti-double stranded (ds) DNA autoantibodies are iconic biomarkers in systemic lupus erythematosus (SLE) used for diagnosis and monitoring disease. They are, however, limited in predicting clinical features of SLE. The aim of this study was to molecularly profile anti-dsDNA at the immunoglobulin heavy chain variable region (IGHV) to determine any associations with SLE manifestations.

 

Methods: Anti-dsDNA immunoprecipitates from 32 patients were profiled using mass spectrometry (MS). IGHV subfamilies were correlated with active disease manifestations as defined by the SLE disease activity index (SLEDAI)-2K.

 

Results: Anti-dsDNA were chiefly IgG1 and IgG3, and belong to the IGHV3 subfamily. We found significant associations with IGHV3-15 and neuropsychiatric lupus (relative risk [RR] 5.7); and IGHV3-21, IGHV3-23 and IGHV4-34 and leukopaenia (RR 13.70, 2.14 and 10.29 respectively). There were no significant associations found with any subfamilies and lupus nephritis.

 

Conclusions: MS offers greater resolution of autoantibody profiling beyond what the routine diagnostic laboratory can offer. This improves predictive medicine and has the potential to revolutionise modern-day immunopathology practice.

Contributions:

AL: conceptualisation, data acquisition, data analyses
MWL: conceptualisation, resources
DS: resources
DB: data contributions, resources
TPG: conceptualisation, resources
JJW: conceptualisation, data analyses