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Identification of p...
Identification of proteinase 3 autoreactive CD4+T cells and their T-cell receptor repertoires in antineutrophil cytoplasmic antibody-associated vasculitis
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- Sharma, Ravi Kumar (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Yoosuf, Niyaz (författare)
- Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Afonso, Marcelo (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Scheffschick, Andrea (författare)
- Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Avik, Aune (författare)
- Karolinska Institutet,Acad Ctr Specialists, Sweden
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- Bartoletti, Alice (författare)
- Univ Pavia, Italy
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- Horuluoglu, Begum (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Boada, Juan Sebastian Diaz (författare)
- Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Boddul, Sanjay Kumar (författare)
- Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Jonasdottir, Asta Dogg (författare)
- Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Lovstrom, Bjorn (författare)
- Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden
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- Brauner, Hanna (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden
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- Raposo, Bruno (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Chemin, Karine (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Bruchfeld, Annette (författare)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Njurmedicinska kliniken US,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden
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- Gunnarsson, Iva (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Univ Hosp, Sweden
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- Malmstrom, Vivianne (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst, Sweden; Karolinska Inst, Sweden
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(creator_code:org_t)
- ELSEVIER SCIENCE INC, 2023
- 2023
- Engelska.
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Ingår i: Kidney International. - : ELSEVIER SCIENCE INC. - 0085-2538 .- 1523-1755. ; 103:5, s. 973-985
- Relaterad länk:
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https://doi.org/10.1...
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease involving autoreactivity to proteinase 3 (PR3) as demonstrated by presence of ANCAs. While autoantibodies are screened for diagnosis, autoreactive T cells and their features are less well-studied. Here, we investigated PR3-specific CD4+T cell responses and features of autoreactive T cells in patients with PR3-AAV, using a cohort of 72 patients with either active or inactive disease. Autoreactive PR3-specific CD4+T cells producing interferon g in response to protein stimulation were found to express the G-protein coupled receptor 56 (GPR56), a cell surface marker that distinguishes T cells with cytotoxic capacity. GPR56+CD4+T cells were significantly more prominent in the blood of patients with inactive as compared to active disease, suggesting that these cells were affected by immunosuppression and/or that they migrated from the circulation to sites of organ involvement. Indeed, GPR56+CD4+T cells were identified in T-cell infiltrates of affected kidneys and an association with immunosuppressive therapy was found. Moreover, distinct TCR gene segment usage and shared (public) T cell clones were found for the PR3-reactive TCRs. Shared T cell clones were found in different patients with AAV carrying the disease-associated HLA- DP allele, demonstrating convergence of the autoreactive T cell repertoire. Thus, we identified a CD4+T cell signature in blood and in affected kidneys that display PR3 autoreactivity and associates with T cell cytotoxicity. Our data provide a basis for novel rationales for both immune monitoring and future therapeutic intervention in PR3-AAV.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- KEYWORDS; ANCA-associated vasculitis; autoimmunity; PR3; T-cell recep; tors; T cells
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- art (ämneskategori)
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- Av författaren/redakt...
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Sharma, Ravi Kum ...
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Yoosuf, Niyaz
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Afonso, Marcelo
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Scheffschick, An ...
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Avik, Aune
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Bartoletti, Alic ...
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visa fler...
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Horuluoglu, Begu ...
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Boada, Juan Seba ...
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Boddul, Sanjay K ...
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Jonasdottir, Ast ...
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Lovstrom, Bjorn
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Brauner, Hanna
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Raposo, Bruno
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Chemin, Karine
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Bruchfeld, Annet ...
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Gunnarsson, Iva
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Malmstrom, Vivia ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
- Artiklar i publikationen
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Kidney Internati ...
- Av lärosätet
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Linköpings universitet
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Karolinska Institutet