AB0008 ROLE OF IL-23/TH17 AXIS CYTOKINES IN RHEUMATOID ARTHRITIS

Abstract

BackgroundRheumatoid arthritis (RA) is an autoimmune inflammatory arthritis driven by an inflammatory cascade of different cytokine families. IL-23/Th17 axis cytokine (IL-23, IL-17) has been studied as a key pathway for disease development and its association with disease severity, joint erosion and functional outcome [1], but the data supplementing to support the hypothesis is lacking and conflicting. Also, there is a paucity of data on the role of IL-23/Th17/IL-17 axis cytokines in an Indian subset of patients.ObjectivesThe objective was to find the correlation between serum cytokines (IL-17, IL-23) and clinical parameters of Rheumatoid arthritis patients, e.g., disease activity (DAS28) and functional status.MethodsThis cross-sectional observational study was conducted in General Medicine OPD from 2021 to 2022. ACR/EULAR 2010 classification criteria was used to diagnose RA. Eighty-four consecutive RA patients were recruited after taking consent. Serum IL-17 and IL-23 levels were measured by the ELISA method. Clinical and laboratory parameters, DAS28-ESR, and HAQII were recorded. Data were analyzed to find the correlation between cytokine and disease parameters, and compare cytokine levels in different subgroups.ResultsThe study showed a higher proportion of females than males (n=76,90.5% vs n=8,9.5%). 14.28%(n=12) cases were elderly RA. 90.5% were taking cDMARDs, whereas 48.8% (n=41) were steroid users. Majority of cases, 57.14% (n=48) had high disease activity, whereas 25% (n=21) had moderate disease activity. Cases achieved remission was 5.95%. The median value of serum IL-17 and IL-23 were 103.72 pg/ml (IQR=39.91-524.13) and 981.87 pg/ml (IQR=793.25-1205.0), respectively.Swollen joint count, but not tender joint count, correlated positively with both IL-17 and IL-23 levels (rs=0.229, p=0.036;rs=0.098, p=0.016, respectively). Among the inflammatory marker, only CRP correlated positively with IL-23 (rs=0.269, p=0.014). Both IL-17 and IL-23 levels showed an insignificant, weak positive correlation with the disease activity DAS28 (rs=0.183, p=0.097 &rs=0.125, p=0.259), respectively. There was no difference in IL-17 and IL-23 levels among the disease severity group (p=0.130 & p=0.215). It was also noted that IL-17 was positively correlated with IL-23 (rs=0.221, p=0.044). Among the cytokines, only IL-23 had shown a statistically positive correlation with functional status (HAQII) (rs=0.284, p=0.009).IL-23 level differed significantly between males and females (p=0.013). Also, advanced RA had higher IL-17 level than early RA (p=0.028). Neither IL-17 nor IL-23 level showed any difference between the subgroup e.g., age (younger RA vs elderly RA), obesity (obese vs nonobese), DMARDs or steroid (user vs naïve), serology status (RF+ vs RF- & CCP+ vs CCP-).ConclusionSerum IL-17 levels were high in advanced RA as compared to early RA. Both IL-17 and IL-23 correlated positively with the swollen joint count. Only IL-23 was directly correlating with CRP and functional status. Both IL-17 and IL-23 had a weak, insignificant positive correlation with disease activity, and there was no difference in cytokines level among severity classes. Even cDMARD/steroid use did not affect the cytokines level.IL-17 receptor activation triggers transformations of acute synovitis to chronic persistent arthritis [2]. IL-23/IL-17 may be a factor for advanced/erosive disease develoment, which need further research. Hence, blocking IL-23 and IL-17 at an early stage may diminish IL-17 activity, retard the progression to chronic inflammatory arthritis and advanced disease.