Identification of cellular and serum biomarkers indicating response to methotrexate (MTX) treatment in patients with juvenile uveitis
Final Report Abstract
The term “uveitis” describes an inflammation of the vascular layers of the interior of the eye. Uveitis in pediatric / adolescent patients is frequently observed in association with juvenile idiopathic arthritis (JIA). Idiopathic anterior uveitis (IAU) is a disease entity with clinically nearly identical manifestation and ocular findings, but occurs without a systemic association, which is why both JIAU and IAU are managed according to identical therapeutic principles. Frequently, a systemic anti-inflammatory therapy with so-called immune-modulating diseasemodifying antirheumatic drugs (DMARDs) is necessary in pediatric uveitis to control inflammation and prevent loss of vision. The first-line medication of choice for JIA without ocular involvement, JIAU and IAU is methotrexate (MTX). In case of incomplete therapeutic response or severe side effects of this drug, Adalimumab (a so-called TNF inhibitor) would be employed as second-line medication (instead of or in addition to MTX). A full anti-inflammatory effect of both drugs can only be expected after regular administration for several weeks to months, which is why the therapeutic effectiveness in an individual patient cannot be evaluated until after about 4 months on average (however, individual patients might respond after 6 months only). Only then is it possible to distinguish between so-called responders (probably about 70% of patients in case of MTX and 80-90% in case of Ada), in whom inflammation responds well to the therapy, and non-responders, who need to be switched to or additionally receive another DMARD. The underlying pathogenetic mechanisms of both arthritis in JIA and pediatric uveitis are largely unknown. According to the present state of knowledge, autoimmunological reactions of the adaptive and the innate immune system in genetically predisposed patients can contribute to this disease. Observations from adult patients with uveitis indicate that distinct immune cell subsets (especially so-called monocytes and T cells) play a role in the course of disease. Our project aims to increase the knowledge on pediatric uveitis by assessing the role of several immune cell subsets in the course of disease, especially in patients with active disease prior to initiation of systemic therapy and after several months of treatment with MTX and/or Adalimumab. This might, in future, help to better assess therapeutic response as well as aid in the clinician’s decision to choose the most promising systemic medication.
Publications
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Abstractband DOG 2023. Die Ophthalmologie, 120(S2), 71-253.
Schell M. ... & Baquet-Walscheid, K.
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Congress of the International Ocular Inflammation Society 2023: Identifying Cellular Biomarkers in Peripheral Blood in Anterior Uveitis in Childhood.
Schell M. ... & Baquet-Walscheid, K.
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Annual Congress of the German Ophthalmological Society (DOG) 2024: Plasmakonzentration von sCD73 und S100A8/A9 bei anteriorer Uveitis im Kindesalter
Schell M. ... & Baquet-Walscheid, K.
