Analysis of accumulated T cell clonotypes in patients with systemic lupus erythematosus

Abstract

Objective To compare the accumulated T cell clonotypes in peripheral blood (PB) samples obtained at various times, and the accumulated T cell clonotypes in a PB sample and in an affected kidney, from patients with systemic lupus erythematosus (SLE). Methods Peripheral blood mononuclear cells (PBMC) were obtained at 2–4 different times from each of 5 SLE patients, with or without flare‐up of the disease; in addition, a biopsied kidney tissue sample was obtained from 1 of the patients. RNA was extracted from each sample and complementary DNA was prepared. Genes that encode the variable region of T cell receptor (TCR) B chains (BV) of 3 BV families, 5S1, 8, and 14, were amplified by reverse transcription–polymerase chain reaction (PCR), and the PCR products were cloned for sequencing. Results A total of 877 cloned TCR genes was detected in the PBMC samples and the kidney sample. Oligoclonal T cell expansion was detected in 34 of the 36 PCR‐amplified BV samples from PBMC (amplification of 3 BV families in 2–4 samples from 5 patients). The composition of clonally expanded T cell clonotypes was relatively stable in the patients with inactive SLE. In contrast, the composition of clonotypes in the PB changed drastically after the patient experienced the active phase of the disease. T cell clonotypes that had accumulated in the kidney appeared to be restricted and distinct from those that had accumulated in the PB of the same patient. Conclusion Different T cell clonotypes expand at different times and at different sites in patients with active SLE. The sensitizing antigens may change over the course of the disease and may be different at each site.

Structural Analysis of TCRα and β Chains from Human T‐Cell Clones Specific for Small Nuclear Ribonucleoprotein Polypeptides Sm‐D, Sm‐B and U1–70 kDa: TCR Complementarity Determining Region 3 Usage Appears Highly Conserved

“…In a recent paper by Kato et al [33] oligoclonal expansion of T-cell clonotypes was identified in the PBL of SLE patients. They identified several identical amino acid residues within the CDR3 which are common.…”

Longitudinal analysis of peripheral blood T cell receptor diversity in patients with systemic lupus erythematosus by next-generation sequencing

“…T cells play an essential role in SLE pathogenesis [1–5]. Clonal expansion of T cells have been observed in SLE patients’ peripheral blood (PB) [6–12] and various organs such as skin [13], kidney [8, 14–16] and gastrointestinal tract [17] where they may be reactive to local antigens and drive tissue inflammation and injury. In vitro studies show that T cells from SLE patients can recognize and proliferate in response to specific autoantigens such as nucleosomal histones [2, 18] and U1 small nuclear ribonucleoprotein A [19, 20].…”

Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in SLE patients: Glycated-histones as likely trigger for SLE?

“…SLE is a disorder of unknown etiology characterized by marked diversity of organ involvement and fluctuations in disease activity. The disease display a wide range of clinical manifestations such as production of antinuclear autoantibodies, formation of immune complexes, decreased serum complement levels and lymphocytopinea [29]. The initial immunizing agents that cause SLE are unknown but characteristics of immune response in SLE suggest that it is an antigen driven condition.…”