V-J combinations of T-cell receptor predict responses to erythropoietin in end-stage renal disease patients

Wong, Henry Sung-Ching; Chang, Che‐Mai; Kao, Chih-Chin; Hsu, Yi‐Hsiang; Xiao, Lei; Chang, Wen-Chang; Wu, Mai‐Szu; Chang, Wei‐Chiao

doi:10.1186/s12929-017-0349-5

Cited by 14 publications

(9 citation statements)

References 27 publications

(23 reference statements)

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“…Peripheral blood samples were harvested from RA patients and processed into peripheral blood mononuclear cells (PBMCs) using Histopaque separation as previously described [22]. Briefly, whole blood samples were mixed 1 : 1 with phosphate-buffered saline (PBS) and layered on top of Histopaque (Sigma-Aldrich, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies

et al. 2019

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Rheumatoid arthritis (RA) is a systematic autoimmune disease, predominantly causing chronic polyarticular inflammation and joint injury of patients. For the treatment of RA, biologic disease-modifying antirheumatic drugs (bDMARDs) have been used to reduce inflammation and to interfere with disease progression through targeting and mediating the immune system. Although the therapeutic effects of bDMARDs in RA patients have been widely reported, whether these drugs also play important roles in T-cell repertoire status is still unclear. We therefore designed the study to identify the role of T-cell repertoire profiles in RA patients with different types of bDMARD treatments. A high-throughput sequencing approach was applied to profile the T-cell receptor beta chain (TCRB) repertoire of circulating T lymphocytes in eight patients given adalimumab (anti-TNF-α) with/without the following use of either rituximab (anti-CD20) or tocilizumab (anti-IL6R). We subsequently analyzed discrepancies in the clonal diversity and CDR3 length distribution as well as usages of the V and J genes of TCRB repertoire and interrogated the association between repertoire diversity and disease activities followed by the treatment of bDMARDs in these RA patients. All groups of patients showed well-controlled DAS28 scores (<2.6) after different treatment regimens of drugs and displayed no significant statistical differences in repertoire diversity, distribution of CDR3 lengths, and usage of V and J genes of TCRB. Nonetheless, a trend between overall TCRB repertoire diversity and disease activity scores in all bDMARD-treated RA patients was observed. Additionally, age was found to be associated with repertoire diversity in RA patients treated with bDMARDs. Through the profiling of the TCR repertoire in RA patients receiving different biologic medications, our study indicated an inverse tendency between TCR repertoire diversity and disease activity after biologic treatment in RA patients.

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Section: Methodsmentioning

confidence: 99%

Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies

et al. 2019

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“…Furthermore, T-cell repertoire (TCR) complexity was revealed to predict the EPO responsiveness. Thus, TCR repertoire diversity may indicate the immune responses to infection [25]. Malnutrition, inflammation, and atherosclerosis syndrome, characterized by patients with renal failure, are predictive of poor outcomes [26].…”

Section: Discussionmentioning

confidence: 99%

Association of endothelin genetic variants and hospitalized infection complications in end-stage renal disease (ESRD) patients

Cheng

Wang

et al. 2019

BMC Nephrol

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Background Infection is the second most common cause of mortality for patients with end-stage renal disease (ESRD), accompanying with immune dysfunction. Endothelin ( EDN ) is known to be related to inflammation; however, it is unknown whether genetic variants of the EDN gene family are associated with increased risk of hospitalized infection events. Methods Nineteen tagging single-nucleotide polymorphisms (tSNPs) of the EDN gene family were selected for genotyping a cohort of 190 ESRD patients. Patient demographics were recorded, the subtypes of infection events were identified, and association analysis between the EDN genetic variants and hospitalized infection events was performed. Results In this study, 106 patients were hospitalized for infection events. The leading events were pneumonia, bacteremia, and cellulitis. The minor allele of rs260741, rs197173, and rs926632 SNPs of EDN3 were found to be associated with reduced risk of hospitalized bacteremia events. Conclusions The minor allele of rs260741, rs197173, and rs926632 in EDN3 were associated with reduced risk of hospitalized bacteremia events in ESRD patients. Electronic supplementary material The online version of this article (10.1186/s12882-019-1349-3) contains supplementary material, which is available to authorized users.

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“…Gene segments were assigned according to published germline sequences for the TCR β gene segments as listed in the ImMunoGeneTics database ( 17 ). The CDR3 of the TCRβ chain was defined to include those residues located between the conserved cysteine (C104) of FR3 and the conserved phenylalanine (F118) of FR4 ( 18 ).…”

Section: Methodsmentioning

confidence: 99%

Replacement of TCR Dβ With Immunoglobulin DH DSP2.3 Imposes a Tyrosine-Enriched TCR Repertoire and Adversely Affects T Cell Development

et al. 2020

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Enrichment for tyrosine in immunoglobulin CDR-H3 is due in large part to natural selection of germline immunoglobulin D H sequence. We have previously shown that when D H sequence is modified to reduce the contribution of tyrosine codons, epitope recognition is altered and B cell development, antibody production, autoantibody production, and morbidity and mortality following pathogen challenge are adversely affected. TCRβ diversity (Dβ) gene segment sequences are even more highly conserved than D H , with trout Dβ1 identical to human and mouse Dβ1. We hypothesized that natural selection of Dβ sequence also shapes CDR-B3 diversity and influences T cell development and T cell function. To test this, we used a mouse strain that lacked Dβ2 and contained a novel Dβ1 allele ( DβYTL ) that replaces Dβ1 with an immunoglobulin D H , DSP2.3. Unlike Dβ1, wherein glycine predominates in all three reading frames (RFs), in DSP2.3 there is enrichment for tyrosine in RF1, threonine in RF2, and leucine in RF3. Mature T cells using DβYTL expressed TCRs enriched at particular CDR-B3 positions for tyrosine but depleted of leucine. Changing Dβ sequence altered thymocyte and peripheral T cell numbers and the T cell response to an ovalbumin immunodominant epitope. The differences in tyrosine content might explain, at least in part, why TCRs are more polyspecific and of lower affinity for their cognate antigens than their immunoglobulin counterparts.

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V-J combinations of T-cell receptor predict responses to erythropoietin in end-stage renal disease patients

Cited by 14 publications

References 27 publications

Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies

Characterization of T-Cell Receptor Repertoire in Patients with Rheumatoid Arthritis Receiving Biologic Therapies

Association of endothelin genetic variants and hospitalized infection complications in end-stage renal disease (ESRD) patients

Replacement of TCR Dβ With Immunoglobulin DH DSP2.3 Imposes a Tyrosine-Enriched TCR Repertoire and Adversely Affects T Cell Development

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