Assessment of variation in B-cell receptor heavy chain repertoire in patients with end-stage renal disease by high-throughput sequencing

Lei Wang,Yong Dai,Song Liu,Liusheng Lai,Qiang Yan,Huaizhou Chen,Jiaxing Zhang,Weiguo Sui

doi:10.1080/0886022x.2018.1487862

Lei Wang, Yong Dai + Show 6 more

Open Access

https://doi.org/10.1080/0886022x.2018.1487862

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Abstract

Background/Aims: End-stage renal disease (ESRD), characterized by progressive loss of rental function during the disease course, has been reported to be correlated with immune dysregulation. To date, a majority of previous studies on immune response to ESRD have been focused on the T-cell response. This prospective study was to assess the B-cell receptor (BCR) heavy chain repertoire in ESRD patients.Materials and methods: A total of 10 ESRD patients and six healthy controls were prospectively enrolled in this study. BCR immunoglobulin heavy chain (IGH) repertoire in the peripheral blood from ESRD patients and healthy individuals were analyzed by means of next generation sequencing (NGS) in combination with multiplex PCR, Illumina sequencing, and the international ImMunoGeneTics database (IMGT).Results: Abnormal BCR complementary-determining region 3 (CDR3) sequences were identified in relation to ESRD. We also found that the degree of the B-cell clonal expansion in the ESRD group was significantly greater than that in the control group (p < .05), whereas the distributions of BCR CDR3, V, D, J, and V–J gene segments were comparable between the ESRD and control groups. T-test for analysis of the distribution ratio of the V, D, J, and V–J genes revealed five up-regulated genes and nine down-regulated genes associated with ESRD, and there were significant differences between the ESRD and control groups (p < .05).Conclusions: We have provided a successful approach to analyzing peripheral B-cell repertoire in ESRD patients, and the results suggest a direct correlation between the BCR repertoire and ESRD. The ESRD-specific BCR CDR3 sequences may hold promise for potentially therapeutic benefit.

Highlights

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its prevalence remains on the rise globally as a result of increasing patients with diabetes and hypertension, which have been identified as major risk factors for CKD
high throughput sequencing (HTS) was conducted to capture a high resolution of the nucleotide and amino acid sequences of the B-cell receptor (BCR) H chain complementary-determining region 3 (CDR3) region of the B cells from the peripheral blood in ten end-stage renal disease (ESRD) patients and six normal control individuals
The total reads sequences, BCR sequences, in-frame sequences, total immunoglobulin heavy chain (IGH) CDR3 sequences, unique CDR3 nt sequences, unique CDR3 aa sequences, highly enpended clone (HEC) number, and HEC ratio were shown in Table 1, in which HEC was defined as the amount of a CDR3 sequence greater than 0.1% of the total amount of CDR3

Summary

Introduction

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its prevalence remains on the rise globally as a result of increasing patients with diabetes and hypertension, which have been identified as major risk factors for CKD. A large proportion of CKD patients may progress to develop eventually end-stage renal disease (ESRD), known as end-stage kidney disease. The incidence rates of ESRD in patients with diabetes and hypertension are increasing.

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