Jüvenil Dermatomiyozit Hastalarının Kas Biyopsilerinde Yardımcı T Hücre Profilleri

Abstract

ABSTRACT SAG, E., T helper cell profile in the muscle biopsies of juvenile dermatomyositis patients. Hacettepe University Medical Faculty, Thesis in Pediatrics. Ankara, 2015. Juvenile dermatomyositis (JDM) is an important disease without an enlightened pathogenesis, which causes severe morbidity and high mortality if untreated. Autoimmunity, inflammation and vasculopathy are considered the basic pathogenetic mechanisms. Muscle involvement is the most important manifestation of the disease. In this study, we aimed to define the T helper cell profile in the muscle biopsies of JDM patients diagnosed at Hacettepe University İhsan Doğramacı Children’s Hospital, Pediatric Pathology Unit, which is one of the largest and most experienced muscle biopsy centers in Turkey. In addition, other components of the inflammatory infiltration were assessed. 26 patients (13 female, 13 male) with sufficient muscle tissue were included in the study. Immunohistochemical expression of CD3, CD20, CD138, CD68, IL-17, Foxp3, IFN-ɣ, IFN-alpha and IL-4 and their clinicopathological correlations were studied and muscle biopsies were scored using the JDM muscle biopsy scoring tool. The mean JDM biopsy score was 17,6, meaning moderate to severe muscular involvement. Inflammatory cells were in small clusters in perimysium and perivascular area or scattered throughout the endomysium in most biopsies, however in two biopsies lymphoid follicle like like big clusters were observed and in one there was a very dense and diffuse inflammatory infiltration nearly destroying all the muscle architecture. As for T helper cell subtypes, 80% of the biopsies were Th1 positive, 92% Th17 positive and 30% Treg positive. No IL-4 positive inflammatory cell was detected in any of the muscle biopsies. Only two biopsies showed IFN-alpha positivity. 73% of the biopsies had T cells, 88% had B cells, 57% had plasma cells and 100% had macrophages. From the clinical aspect, serum creatine kinase level was not correlated with any parameter, however Medical Research Council (MRC) score for muscle strength was correlated with muscle fiber domain scores, visual analogue score of the pathologist and the macrophage infiltration scores. Visual analogue score of the pathologist was strongly correlated with both clinical and histopathological features. Based on these results, it can be concluded that B cells, macrophages, plasma cells and T cells constitute the inflammatory milieu of the JDM muscle biopsies; JDM is a disease related with Th1 ! ! vii! and Th17 T helper cell subtypes; Th2 cells are not involved in the pathogenesis; Tregs are present but not fully functional. Key words: Juvenile dermatomyositis, T helper cell, cytokine, muscle biopsy Supported by Hacettepe University Scientific Research Projects Coordination Unit, BAB6083 project, Project No: 014 D04 101 013