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

Ren Fail. 2019 Nov;41(1):1-13. doi: 10.1080/0886022X.2018.1487862.

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.

Keywords: B-cell receptor; B-cell response; End-stage renal disease; immune repertoire; next generation sequencing.

MeSH terms

  • Adult
  • Antigens, Differentiation, B-Lymphocyte / genetics*
  • B-Lymphocytes / metabolism*
  • Case-Control Studies
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Kidney Failure, Chronic / immunology*
  • Middle Aged
  • Prospective Studies
  • Young Adult

Substances

  • Antigens, Differentiation, B-Lymphocyte

Grants and funding

This project was supported by the Technology Plan of Shenzhen, Guangdong [Grant No. JCYJ20160422150329190], the China Postdoctoral Science Foundation [Grant No. 2017M610575], and the Guilin Scientific Research and Technology Development Program [Grant No. 20170117–1].