Short-term assessment of BCR repertoires of SLE patients after high dose glucocorticoid therapy with high-throughput sequencing.

Bin Shi,Xinsheng Yao,Rui Ma,Suhong Sun,Long Ma,Chunmei Liu,Qingqing Ma,Jiang Yu

doi:10.1186/s40064-016-1709-4

Bin Shi, Xinsheng Yao + Show 6 more

Open Access

https://doi.org/10.1186/s40064-016-1709-4

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Abstract

We analyze and assess BCR repertoires of SLE patients before and after high dose glucocorticoid therapy to address two fundamental questions: (1) After the treatment, how the BCR repertoire of SLE patient change on the clone level? (2) How to screen putative autoantibody clone set from BCR repertoire of SLE patients? The PBMCs of two SLE patients (P1 and P2) at different time points were collected, and DNA of these samples were extracted. High-throughput sequencing technology was applied in detection of BCR repertoire. Finally, we used bioinformatic methodology to analyse sequence data. We found that these two patients lost some IGHV3 family genes usage after treatment compared with before treatment. For pairing of IGHV–IGHJ gene, no significant change was shown for each patient. In addition, analyses of the composition of H-CDR3 showed overall AA compositions of H-CDR3 at three time points in each SLE patients were very similar, and the results of H-CDR3 AA usage that had the same length (14 AA) and the same position were similar. Antinuclear antibody tests of SLE patients showed that level of some antinuclear antibodies reduced after treatment; however, there was no sign that the percentage of autoantibody clones in BCR repertoires would reduce. High dose glucocorticoid treatment in short term will have little impact on composition of BCR repertoire of SLE patient. Treatment can reduce the amount of autoantibody in the protein level, but may not reduce the percentage of autoantibody clones in BCR repertoire in the clonal level.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-1709-4) contains supplementary material, which is available to authorized users.

Highlights

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology and abnormal activation of B cells
The treatment can reduce the formation of autoantibody in the protein level, but may not reduce the proportion of autoantibody clone in B cell receptor (BCR) repertoire in the clone level
We must be cautious with this, because our result indicates that the BCR repertoire of these two SLE patients did not turn better

Summary

Introduction

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology and abnormal activation of B cells. Various autoantibodies can be detected in the serum of the SLE patients. Among these autoantibodies, anti-dsDNA, anti-SM and anticardiolipin antibodies have important diagnosis value (Hochberg 1997). It is currently considered that, autoreactive B cell and the autoantibodies secreted by plasmocyte are the main factors that directly resulted in pathogen of SLE B cell receptor (BCR), which is on the surface of B cell membrane, is an important functional receptor of B cell, involving in immune response of humoral inducing. BCR is a tetrapeptide chain structure with two heavy chains (IGH) and two light chains (IGL). The heavy chain complementary determining region 3 (H-CDR3) is thought to be the key regions of antigen recognition and combination (Tonegawa 1983; Chothia et al 1989; Padlan 1994; Wilson and Stanfield 1994). As for healthy people, peripheral blood often contains about 3 × 109 BCRs, and the diversity of BCR repertoire or antibody repertoire is produced by multiple mechanism, mainly including rearrangement of various discontinuous V, Shi et al SpringerPlus (2016) 5:75

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