Systemic lupus erythematosus patients contain B-cell receptor repertoires sensitive to immunosuppressive drugs.

Abstract

Immune repertoire (IR) during treatment may be a surrogate biomarker for disease response. Changes of the IR in systemic lupus erythematosus patients in response to immunosuppressive drugs were identified in ten SLE patients. Patients provided peripheral blood mononuclear cells at two time points for sequencing. They were divided into sensitive and nonsensitive groups by their clinical responses to immunosuppressive drugs. After treatment, the BCR expression significantly decreased in patients from the sensitive group while there was no change in patients from the nonsensitive group. IgM comprised a dominant portion of the BCR repertoire and increased slightly in all patients in the sensitive group but decreased in the nonsensitive group. IgA also exhibited opposing changes between the two groups. Shorter CDR3 of TRB and TRG chains occurred in the sensitive group. CDR3 length of IGK decreased significantly in the sensitive group. CDR3 of TCR δ/γ changed distinctly between time points in the sensitive group. Six immune-related genes showed differential expression levels in sensitive and nonsensitive groups. Our study shows that it is BCR repertoire sensitivity to immunosuppressive drugs in SLE patients and sheds light on personalized therapy for SLE.