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 immunerelated 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.

Effect of BAFF blockade on the B cell receptor repertoire and transcriptome in a mouse model of systemic lupus erythematosus

“…Wardemann and Mefre previously showed that a longer immunoglobulin heavy chain CDR3 correlates with antibody autoreactivity in SLE ( 49 , 50 ). We found that no significant difference in CDR3 mean length of IGHV in BAFF-R-Fc-treated mice compared to those observed in controls, consistent with a previous study ( 47 ). However, the distribution of CDR3 lengths was altered, with the most commonly used length decreasing from 15 amino acids to 14 amino acids.…”

“…As we found the BCR diversity and richness were positively correlated with B cells proportion. Similar outcomes have been reported in patients receiving stable immunosuppressive therapy such as mycophenolate mofetil and leflunomide ( 47 ).…”

“…As we found the BCR diversity and richness were positively correlated with B cells proportion. Similar outcomes have been reported in patients receiving stable immunosuppressive therapy such as mycophenolate mofetil and leflunomide (47). Huang et al reported a notable loss of IGHV4-34 among plasmablasts and a mutated IgM BCR repertoire in belimumab-treated individuals when compared to controls (48).…”

Epigenetic regulation of B cells and its role in autoimmune pathogenesis

“…Compared with those from healthy donors, B cells from SLE patients show increased BCR clonotypes and biased usage of BCR V(D)J genes [ 139 ]. In particular, B cells from SLE patients who are sensitive to immunosuppressive drugs show significantly decreased BCR expression and clonal diversification, while these changes are undetectable in nonsensitive lupus patients, indicating that alterations of the BCR repertoire are associated with sensitivity to immunosuppressive therapy [ 140 ]. It has also been reported that the nonresponse rates to rituximab among RA patients are closely associated with marked disruption of the BCR repertoire, suggesting that BCR clonality may serve as a predictor of the responses of RA patients to B-cell-depletion therapy [ 141 ].…”

Computational detection of antigen specific B cell receptors following immunization

“…1). Identifying B cell receptors (BCRs) that respond to specific antigens is an important goal for describing the dynamics of B cell immunity following vaccination, with potential applications in vaccine development [1][2][3][4][5][6], personalized medicine [7][8][9], and antibody-derived therapeutics [10][11][12][13][14].…”