Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome

Lu, Chenyang; Pi, Xuenan; Xu, Wang‐Dong; Qing, Pingying; Tang, Honghu; Li, Yanhong; Zhao, Yi; Liu, Xiao; Tang, Huairong; Liu, Yi

doi:10.1016/j.ebiom.2022.104252

Cited by 12 publications

(17 citation statements)

References 45 publications

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“…At a pathophysiological level, these risk HLA alleles probably relate to the T cells’ abilities to recognise and engage in Ro/La autoantigens 19. This is supported in part by the recent observations of a higher diversity of T cell clonotypes associated with Ro/La positivity in SS patients 20…”

Section: Discussionmentioning

confidence: 84%

“… 19 This is supported in part by the recent observations of a higher diversity of T cell clonotypes associated with Ro/La positivity in SS patients. 20 …”

Section: Discussionmentioning

confidence: 99%

“…19 This is supported in part by the recent observations of a higher diversity of T cell clonotypes associated with Ro/La positivity in SS patients. 20 The natural molecular evolution and the pathogenesis of autoantibodies is still poorly understood. It is conceivable that dying or apoptotic cells cause the exposure of these RNP autoantigens.…”

Section: Case Reportmentioning

confidence: 99%

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Serological intermolecular epitope spreading in a patient with primary Sjögren’s syndrome

Lee

Lin

2023

BMJ Case Rep

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Sjögren’s syndrome (SS) is one of the prototypic systemic autoimmune diseases characterised by autoreactive T and B cells, sicca symptoms and various extraglandular manifestations. SS is characterised by autoantibodies (anti-Ro52/tripartite motif containing-21 [TRIM21], anti-Ro60 and anti-La) that are important diagnostic biomarkers. Patients have typically stable serostatus; that is, patients who are positive for one or more of these autoantibodies tend to remain thus and vice versa. We describe a rare instance where a woman in her 50s was diagnosed with primary SS and developed new autoantibodies subsequently through serological epitope spreading. She demonstrated primarily glandular features only and clinical stability despite serological evolution. In this case report, we discuss the significance of this molecular feature and the clinical implications for our understanding of autoimmunity.

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Section: Discussionmentioning

confidence: 84%

“… 19 This is supported in part by the recent observations of a higher diversity of T cell clonotypes associated with Ro/La positivity in SS patients. 20 …”

Section: Discussionmentioning

confidence: 99%

Section: Case Reportmentioning

confidence: 99%

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Serological intermolecular epitope spreading in a patient with primary Sjögren’s syndrome

Lee

Lin

2023

BMJ Case Rep

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“…However, findings vary between studies and measures of diversity are highly donor dependent so it is difficult to convert this observation into a tractable biomarker. In IMRDs the same pattern is a feature of pre‐ or early IMRDs with a reduction in diversity associated with oligoclonal expansions a feature of Sjogren's, 45 PMR/GCA, 46 and early RA 47 . This likely represents affinity maturation and epitope spreading of the autoantibody responses leading to responses with greater specificity for targeted self‐antigens and at the same time antibodies recognizing a broader range of self‐antigens 48,49 …”

Section: Immune Phenotyping Of Rheumatic Iraesmentioning

confidence: 91%

Rheumatic complications of checkpoint inhibitors: Lessons from autoimmunity

Reynolds

2023

Immunological Reviews

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SummaryImmune checkpoint inhibitors are now an established treatment in the management of a range of cancers. Their success means that their use is likely to increase in future in terms of the numbers of patients treated, the indications and the range of immune checkpoints targeted. They function by counteracting immune evasion by the tumor but, as a consequence, can breach self‐tolerance at other sites leading to a range of immune‐related adverse events. Included among these complications are a range of rheumatologic complications, including inflammatory arthritis and keratoconjunctivitis sicca. These superficially resemble immune‐mediated rheumatic diseases (IMRDs) such as rheumatoid arthritis and Sjogren's disease but preliminary studies suggest they are clinically and immunologically distinct entities. However, there appear to be common processes that predispose to the development of both that may inform preventative interventions and predictive tools. Both groups of conditions highlight the centrality of immune checkpoints in controlling tolerance and how it can be restored. Here we will discuss some of these commonalities and differences between rheumatic irAEs and IMRDs.

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“…As examples, the clinical severity of tuberculosis is correlated with restricted TCR diversity, as is the escape of hepatitis C virus from cytotoxic T cell surveillance [ 5 , 6 ]. A skewed TCR repertoire can also render individuals vulnerable to auto-immune disease and/or to inflammatory responses caused by bacterial or viral superantigens [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Microbiome Shapes the T Cell Receptor Repertoire among CD4+CD8+ Thymocytes

et al. 2022

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The microbiome shapes the mature T cell receptor (TCR) repertoire and thereby influences pathogen control. To investigate microbiome influences on T cells at an earlier, immature stage, we compared single-cell TCR transcript sequences between CD4+CD8+ (double-positive) thymocytes from gnotobiotic [E. coli mono-associated (Ec)] and germ-free (GF) mice. Identical TCRβ transcripts (termed repeat, REP) were more often shared between cells of individual Ec mice compared to GF mice (Fishers Exact test, p < 0.0001). Among Ec REPs, a cluster of Vβ genes (Vβ12-1, 12-2, 13-1, and 13-2, termed 12-13) was well represented, whereas 12-13 sequences were not detected among GF REPs (Fishers Exact test, p = 0.046). Vα genes located in the distal region of the TCRα locus were more frequently expressed in Ec mice compared to GF mice, both among REPs and total sequences (Fishers Exact test, p = 0.009). Results illustrate how gut bacteria shape the TCR repertoire, not simply among mature T cells, but among immature CD4+CD8+ thymocytes.

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Clinical significance of T cell receptor repertoire in primary Sjogren's syndrome

Cited by 12 publications

References 45 publications

Serological intermolecular epitope spreading in a patient with primary Sjögren’s syndrome

Serological intermolecular epitope spreading in a patient with primary Sjögren’s syndrome

Rheumatic complications of checkpoint inhibitors: Lessons from autoimmunity

Microbiome Shapes the T Cell Receptor Repertoire among CD4+CD8+ Thymocytes

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