The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis
Abstract Objectives T regulatory cells (Tregs) are a heterogeneous group of immunoregulatory cells that dampen self‐harming immune responses and prevent the development of autoimmune diseases. In anti‐neutrophil cytoplasmic autoantibody (ANCA) vasculitis, Tregs possess diminished suppressive capacit...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.1428 |
| _version_ | 1811211038053367808 |
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| author | Christian Agosto‐Burgos Eveline Y Wu Marie A Iannone Yichun Hu Susan L Hogan Candace D Henderson Kristin B Kennedy Lauren Blazek Carolina A Herrera Dominique Munson Ronald J Falk Dominic J Ciavatta Meghan E Free |
| author_facet | Christian Agosto‐Burgos Eveline Y Wu Marie A Iannone Yichun Hu Susan L Hogan Candace D Henderson Kristin B Kennedy Lauren Blazek Carolina A Herrera Dominique Munson Ronald J Falk Dominic J Ciavatta Meghan E Free |
| author_sort | Christian Agosto‐Burgos |
| collection | DOAJ |
| description | Abstract Objectives T regulatory cells (Tregs) are a heterogeneous group of immunoregulatory cells that dampen self‐harming immune responses and prevent the development of autoimmune diseases. In anti‐neutrophil cytoplasmic autoantibody (ANCA) vasculitis, Tregs possess diminished suppressive capacity, which has been attributed to the expression of a FOXP3 splice‐variant lacking exon 2 in T cells (FOXP3Δ2 CD4+ T cells). However, the suppressive capacity of Tregs varies between subsets. We evaluated the frequency of Treg subsets in ANCA vasculitis as a potential explanation for diminished suppressive capacity. Methods We developed a custom mass cytometry panel and performed deep immune profiling of Tregs in healthy controls, patients with active disease and in remission. Using these data, we performed multidimensional reduction and discriminant analysis to identify associations between Treg subsets and disease activity. Results Total Tregs were expanded in ANCA vasculitis, which was associated with remission and the administration of rituximab and/or prednisone. The frequency of FOXP3Δ2 CD4+ T cells did not distinguish disease activity and this population had high expression levels of CD127 and lacked both CD25 and Helios, suggesting that they are not conventional Tregs. The frequency of CXCR3+, CD103+ and CCR7+ Tregs distinguished disease activity, and the combination of the frequency of these three Treg subsets segregated active patients from patients in remission and healthy controls. From these three subsets, the frequency of CXCR3+ Tregs distinguished patients with active disease with renal involvement. Conclusion Treg heterogeneity can discriminate disease activity and should be explored as a biomarker of disease activity in ANCA vasculitis. |
| first_indexed | 2024-04-12T05:06:06Z |
| format | Article |
| id | doaj.art-680b925a8fee483e85a7f6dab3ad0451 |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-04-12T05:06:06Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-680b925a8fee483e85a7f6dab3ad04512022-12-22T03:46:53ZengWileyClinical & Translational Immunology2050-00682022-01-011111n/an/a10.1002/cti2.1428The frequency of Treg subsets distinguishes disease activity in ANCA vasculitisChristian Agosto‐Burgos0Eveline Y Wu1Marie A Iannone2Yichun Hu3Susan L Hogan4Candace D Henderson5Kristin B Kennedy6Lauren Blazek7Carolina A Herrera8Dominique Munson9Ronald J Falk10Dominic J Ciavatta11Meghan E Free12Division of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics University of North Carolina Chapel Hill NC USALineberger Comprehensive Cancer Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USADivision of Nephrology and Hypertension, Department of Medicine, UNC Kidney Center University of North Carolina at Chapel Hill Chapel Hill NC USAAbstract Objectives T regulatory cells (Tregs) are a heterogeneous group of immunoregulatory cells that dampen self‐harming immune responses and prevent the development of autoimmune diseases. In anti‐neutrophil cytoplasmic autoantibody (ANCA) vasculitis, Tregs possess diminished suppressive capacity, which has been attributed to the expression of a FOXP3 splice‐variant lacking exon 2 in T cells (FOXP3Δ2 CD4+ T cells). However, the suppressive capacity of Tregs varies between subsets. We evaluated the frequency of Treg subsets in ANCA vasculitis as a potential explanation for diminished suppressive capacity. Methods We developed a custom mass cytometry panel and performed deep immune profiling of Tregs in healthy controls, patients with active disease and in remission. Using these data, we performed multidimensional reduction and discriminant analysis to identify associations between Treg subsets and disease activity. Results Total Tregs were expanded in ANCA vasculitis, which was associated with remission and the administration of rituximab and/or prednisone. The frequency of FOXP3Δ2 CD4+ T cells did not distinguish disease activity and this population had high expression levels of CD127 and lacked both CD25 and Helios, suggesting that they are not conventional Tregs. The frequency of CXCR3+, CD103+ and CCR7+ Tregs distinguished disease activity, and the combination of the frequency of these three Treg subsets segregated active patients from patients in remission and healthy controls. From these three subsets, the frequency of CXCR3+ Tregs distinguished patients with active disease with renal involvement. Conclusion Treg heterogeneity can discriminate disease activity and should be explored as a biomarker of disease activity in ANCA vasculitis.https://doi.org/10.1002/cti2.1428ANCA vasculitisautoimmune diseaseTregs |
| spellingShingle | Christian Agosto‐Burgos Eveline Y Wu Marie A Iannone Yichun Hu Susan L Hogan Candace D Henderson Kristin B Kennedy Lauren Blazek Carolina A Herrera Dominique Munson Ronald J Falk Dominic J Ciavatta Meghan E Free The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis Clinical & Translational Immunology ANCA vasculitis autoimmune disease Tregs |
| title | The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis |
| title_full | The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis |
| title_fullStr | The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis |
| title_full_unstemmed | The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis |
| title_short | The frequency of Treg subsets distinguishes disease activity in ANCA vasculitis |
| title_sort | frequency of treg subsets distinguishes disease activity in anca vasculitis |
| topic | ANCA vasculitis autoimmune disease Tregs |
| url | https://doi.org/10.1002/cti2.1428 |
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