Polyarticular juvenile idiopathic arthritis has a distinct co-inhibitor receptor profile

Erdal Sag; Zeynep Balik; Selcan Demir; Ummusen Akca Kaya; Seher Sener; Muserref Kasap Cuceoglu; Erdal Atalay; Sena Bocutcu; Tayfun Vural; Nur Kubra Tasdemir; Busra Aydin; Yelda Bilginer; Bent Deleuran; Seza Ozen

doi:10.1093/rheumatology/keae306

Polyarticular juvenile idiopathic arthritis has a distinct co-inhibitor receptor profile

Erdal Sag^*
, Zeynep Balik
, Selcan Demir
, Ummusen Akca Kaya
, Seher Sener
, Muserref Kasap Cuceoglu
, Erdal Atalay
, Sena Bocutcu
, Tayfun Vural
, Nur Kubra Tasdemir
, Busra Aydin
, Yelda Bilginer
, Bent Deleuran
, Seza Ozen

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Abstract

Objectives: JIA is the most common rheumatic disease of childhood; the pathogenesis is associated with T-cell activation. T-cell activation can be counterbalanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3 and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes. Methods: In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis-related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and SF) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups. Results: The polyarticular JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4 (P<0.001), sPD-1 (P<0.05) and s4-1BB (P<0.05) when compared with the other JIA subgroups and healthy controls. We analysed the cellular surface expression of different co-IRs on the peripheral blood mononuclear cells of different JIA subtypes. Similar to plasma levels, both the percentage (P<0.05) and the mean fluorescence intensity (P<0.01) of CTLA4 expression were higher in the polyarticular JIA subgroup. Conclusion: This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA.

Originalsprog	Engelsk
Tidsskrift	Rheumatology
Vol/bind	64
Nummer	3
Sider (fra-til)	1424-1430
Antal sider	7
ISSN	1462-0324
DOI	https://doi.org/10.1093/rheumatology/keae306
Status	Udgivet - 1 mar. 2025

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@article{d6712295732d4410ae6816fc7a009ea9,

title = "Polyarticular juvenile idiopathic arthritis has a distinct co-inhibitor receptor profile",

abstract = "Objectives: JIA is the most common rheumatic disease of childhood; the pathogenesis is associated with T-cell activation. T-cell activation can be counterbalanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3 and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes. Methods: In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis-related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and SF) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups. Results: The polyarticular JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4 (P<0.001), sPD-1 (P<0.05) and s4-1BB (P<0.05) when compared with the other JIA subgroups and healthy controls. We analysed the cellular surface expression of different co-IRs on the peripheral blood mononuclear cells of different JIA subtypes. Similar to plasma levels, both the percentage (P<0.05) and the mean fluorescence intensity (P<0.01) of CTLA4 expression were higher in the polyarticular JIA subgroup. Conclusion: This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA.",

keywords = "exhaustion, inhibitory receptor, juvenile idiopathic arthritis, T cell",

author = "Erdal Sag and Zeynep Balik and Selcan Demir and Kaya, \{Ummusen Akca\} and Seher Sener and Cuceoglu, \{Muserref Kasap\} and Erdal Atalay and Sena Bocutcu and Tayfun Vural and Tasdemir, \{Nur Kubra\} and Busra Aydin and Yelda Bilginer and Bent Deleuran and Seza Ozen",

year = "2025",

month = mar,

day = "1",

doi = "10.1093/rheumatology/keae306",

language = "English",

volume = "64",

pages = "1424--1430",

journal = "Rheumatology",

issn = "1462-0324",

publisher = "Oxford University Press",

number = "3",

}

TY - JOUR

T1 - Polyarticular juvenile idiopathic arthritis has a distinct co-inhibitor receptor profile

AU - Sag, Erdal

AU - Balik, Zeynep

AU - Demir, Selcan

AU - Kaya, Ummusen Akca

AU - Sener, Seher

AU - Cuceoglu, Muserref Kasap

AU - Atalay, Erdal

AU - Bocutcu, Sena

AU - Vural, Tayfun

AU - Tasdemir, Nur Kubra

AU - Aydin, Busra

AU - Bilginer, Yelda

AU - Deleuran, Bent

AU - Ozen, Seza

PY - 2025/3/1

Y1 - 2025/3/1

N2 - Objectives: JIA is the most common rheumatic disease of childhood; the pathogenesis is associated with T-cell activation. T-cell activation can be counterbalanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3 and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes. Methods: In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis-related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and SF) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups. Results: The polyarticular JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4 (P<0.001), sPD-1 (P<0.05) and s4-1BB (P<0.05) when compared with the other JIA subgroups and healthy controls. We analysed the cellular surface expression of different co-IRs on the peripheral blood mononuclear cells of different JIA subtypes. Similar to plasma levels, both the percentage (P<0.05) and the mean fluorescence intensity (P<0.01) of CTLA4 expression were higher in the polyarticular JIA subgroup. Conclusion: This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA.

AB - Objectives: JIA is the most common rheumatic disease of childhood; the pathogenesis is associated with T-cell activation. T-cell activation can be counterbalanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3 and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes. Methods: In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis-related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and SF) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups. Results: The polyarticular JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4 (P<0.001), sPD-1 (P<0.05) and s4-1BB (P<0.05) when compared with the other JIA subgroups and healthy controls. We analysed the cellular surface expression of different co-IRs on the peripheral blood mononuclear cells of different JIA subtypes. Similar to plasma levels, both the percentage (P<0.05) and the mean fluorescence intensity (P<0.01) of CTLA4 expression were higher in the polyarticular JIA subgroup. Conclusion: This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA.

KW - exhaustion

KW - inhibitory receptor

KW - juvenile idiopathic arthritis

KW - T cell

UR - https://www.scopus.com/pages/publications/86000154127

U2 - 10.1093/rheumatology/keae306

DO - 10.1093/rheumatology/keae306

M3 - Journal article

C2 - 38781517

AN - SCOPUS:86000154127

SN - 1462-0324

VL - 64

SP - 1424

EP - 1430

JO - Rheumatology

JF - Rheumatology

IS - 3

ER -

Polyarticular juvenile idiopathic arthritis has a distinct co-inhibitor receptor profile

Abstract

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