Baseline IL-2 and the AIH score can predict the response to standard therapy in paediatric autoimmune hepatitis

Abstract

Although autoimmune hepatitis (AIH) can be treated with corticosteroid-based first-line therapy, incomplete remission is associated with progressive liver fibrosis. So far accepted predictors of the subsequent treatment response of AIH patients are lacking. Therefore, we analysed baseline parameters, including iron homeostasis and cytokine levels, in 60 children with paediatric AIH (pAIH). In contrast to adults, elevated serum markers indicating iron overload were not commonly found in children. Therefore, ferritin was not predictive of the treatment response in pAIH. Although baseline immunoglobulins were lower in pAIH children with subsequent complete biochemical remission (BR) upon standard first-line therapy, only lower AIH scores (≤16 points) could predict BR upon standard therapy in our training and validation cohorts. Additionally, higher baseline IL-2 and MCP-1/CCL2 levels were associated with BR in a sub-cohort. A combined score of IL-2 level and a simplified AIH score predicted treatment response more precisely than both parameter alone in this sub-cohort. In conclusion, the baseline AIH score could be validated as a predictor of treatment response in pAIH. Additionally, low baseline IL-2 may help identify children who need salvage therapy. This could be important because the use of low-dose IL-2 therapies is being tested in various autoimmune diseases.

Soluble Fgl2 restricts autoimmune hepatitis progression via suppressing Tc17 and conventional CD8+ T cell function

“…Attempts to predict AIH etiology and prognosis with serum cytokines have elicited many focal points. However, the results based on serum levels of IL‐2, IL‐4, IL‐6, IL‐10, IP‐10, TGF‐β, IFN‐γ and TNF‐α remain controversial . In our cohort study, no significant alterations of cytokines such as IL‐2 (AIH 7.54 ± 0.35 versus health 7.61 ± 0.34), IL‐6 (AIH 8.86 ± 1.48 versus health 7.47 ± 2.87), IL‐4 (AIH 5.74 ± 1.28 versus health 5.25 ± 0.71), IL‐10 (4.87 ± 0.3 versus health 5.90 ± 1.74) and TNF‐α (AIH 3.98 ± 1.28 versus health 2.94 ± 1.24) were observed in AIH patients.…”

Exploring the Pathogenic Role and Therapeutic Implications of Interleukin 2 in Autoimmune Hepatitis

“…The baseline circulating level of IL-2 in children with autoimmune hepatitis is predictive of the biochemical response to glucocorticoid therapy when combined with a simplified scoring system, and low baseline IL-2 levels may augur a poor treatment outcome [201] (Table 4). Furthermore, disproportionate reduction in the intrahepatic Tregs during standard glucocorticoid-based therapy has been accompanied by a tenfold decrease in the circulating IL-2 level that may predispose to an incomplete treatment response [202] or relapse after drug withdrawal [203].…”

“…These observations in concert with clinical experiences assessing IL-2 therapy in other autoimmune diseases [71][72][73][74][77][78][79] have justified investigation of IL-2 supplementation as a therapeutic intervention in autoimmune hepatitis [80]. [194][195][196]201] Fewer Treg numbers and function [198,279,280] Poor glucocorticoid response [201]…”

Novel Diagnostic and Therapeutic Strategies in Juvenile Autoimmune Hepatitis

“…Liver-derived lymphocytes from patients with PSC show reduced expression of the IL-2 receptor (171). In AIH patients, baseline and under therapy IL-2 serum levels seems lower than controls (172) and children with higher baseline levels of IL-2 more easily achieve biochemical remission (173).…”