AUTHOR=Izati Aziz Farah , Mohd Shukri Nur Diyana , Wan Ghazali Wan Syamimee , Che Hussin Che Maraina , Wong Kah Keng 

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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.690908

DOI=10.3389/fimmu.2021.690908

ISSN=1664-3224

ABSTRACT=<p>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<sup>+</sup> and IL-23R<sup>+</sup> 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<sup>+</sup> and IL-23R<sup>+</sup> 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<sup>+</sup>CD4<sup>+</sup> Th cells of SLE patients demonstrated significantly elevated IL-17RA<sup>+</sup> (<italic>p</italic> = 1.12 x 10<sup>-4</sup>) or IL-23R<sup>+</sup> (<italic>p</italic> = 1.98 x 10<sup>-29</sup>) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (<italic>p</italic> = 8.32 x 10<sup>-5</sup>), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R<sup>+</sup> Th cells population was significantly associated with higher SLEDAI-2K scores (<italic>p</italic> = 0.017). In multivariate analysis, the proportion of IL-23R<sup>+</sup> Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (<italic>p</italic> = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA<sup>+</sup> Th cells, and IL-23R<sup>+</sup> 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.</p>