Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and...

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Main Authors: Aziz Farah Izati, Nur Diyana Mohd Shukri, Wan Syamimee Wan Ghazali, Che Maraina Che Hussin, Kah Keng Wong
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-08-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.690908/full
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author Aziz Farah Izati
Aziz Farah Izati
Nur Diyana Mohd Shukri
Nur Diyana Mohd Shukri
Wan Syamimee Wan Ghazali
Wan Syamimee Wan Ghazali
Che Maraina Che Hussin
Che Maraina Che Hussin
Kah Keng Wong
Kah Keng Wong
author_facet Aziz Farah Izati
Aziz Farah Izati
Nur Diyana Mohd Shukri
Nur Diyana Mohd Shukri
Wan Syamimee Wan Ghazali
Wan Syamimee Wan Ghazali
Che Maraina Che Hussin
Che Maraina Che Hussin
Kah Keng Wong
Kah Keng Wong
author_sort Aziz Farah Izati
collection DOAJ
description The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.
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spelling doaj.art-a01d5a0a3a6b4a3dbbf938c8fe5b76602022-12-21T22:28:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-08-011210.3389/fimmu.2021.690908690908Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus PatientsAziz Farah Izati0Aziz Farah Izati1Nur Diyana Mohd Shukri2Nur Diyana Mohd Shukri3Wan Syamimee Wan Ghazali4Wan Syamimee Wan Ghazali5Che Maraina Che Hussin6Che Maraina Che Hussin7Kah Keng Wong8Kah Keng Wong9Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Internal Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaDepartment of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, MalaysiaHospital Universiti Sains Malaysia, Kubang Kerian, MalaysiaThe IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.https://www.frontiersin.org/articles/10.3389/fimmu.2021.690908/fullsystemic lupus erythematosusIL-23/IL-17 axisIL-17IL-23IL-17RAIL-23R
spellingShingle Aziz Farah Izati
Aziz Farah Izati
Nur Diyana Mohd Shukri
Nur Diyana Mohd Shukri
Wan Syamimee Wan Ghazali
Wan Syamimee Wan Ghazali
Che Maraina Che Hussin
Che Maraina Che Hussin
Kah Keng Wong
Kah Keng Wong
Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients
Frontiers in Immunology
systemic lupus erythematosus
IL-23/IL-17 axis
IL-17
IL-23
IL-17RA
IL-23R
title Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients
title_full Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients
title_fullStr Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients
title_full_unstemmed Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients
title_short Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients
title_sort increased il 23r th cells population exhibits higher sledai 2k scores in systemic lupus erythematosus patients
topic systemic lupus erythematosus
IL-23/IL-17 axis
IL-17
IL-23
IL-17RA
IL-23R
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.690908/full
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