Thymus alterations and systemic sclerosis

Ferri, Clodoveo; Colaci, Michele; Battolla, L.; Giuggioli, Dilia; Sebastiani, Marco

doi:10.1093/rheumatology/kei101

Cited by 29 publications

(18 citation statements)

References 18 publications

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“…In addition, focal massive clustering of follicles (>3 follicles per LPF) was considered as an additional criterion of high‐grade TFH. This grading system correlates with findings reported in the literature: few follicles are seen in up to one‐third of the lobules (as in grade 1 TFH) in healthy infants or adults, while TFH of grades 2–3 (in two‐thirds or more lobules) are typical for EOMG but rarely occur in other autoimmune diseases . By contrast, follicular clustering (grade 4 TFH) appears to be almost pathognomonic for EOMG …”

Section: The Thymus In Eomgsupporting

confidence: 87%

Challenging the current model of early‐onset myasthenia gravis pathogenesis in the light of the MGTX trial and histological heterogeneity of thymectomy specimens

Weis

Schalke

Ströbel

et al. 2018

Annals of the New York Academy of Sciences

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The MGTX trial provided evidence that, in general, thymectomy is beneficial in adult patients up to 60 years of age with anti-acetylcholine receptor-positive, nonthymomatous myasthenia gravis (MG). This finding supports the long-held view that the pathogenesis of this type of MG (early-onset MG (EOMG)) starts inside the thymus, results in the long-term intrathymic recruitment of autoantibody-producing B cells and plasma cells, and eventually spreads to the peripheral immune system. However, observed clinical responses to treatment in the MGTX trial were diverse. This might be due to heterogeneous epidemiological and genetic features of EOMG patients and variable durations of corticosteroid treatment before surgery, including a paucity of patients that were corticosteroid naive. Furthermore, the observed histological heterogeneity suggests that a single pathogenetic model may not fully reflect the spectrum of events that modify the course of EOMG. Here, we describe the morphology of the normal and MG-associated thymus, how to evaluate morphological changes, and the current pathogenetic model of EOMG and discuss how it could be refined by integrating MGTX-derived histological findings in thymectomy specimens and associated clinical observations.

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Section: The Thymus In Eomgsupporting

confidence: 87%

Challenging the current model of early‐onset myasthenia gravis pathogenesis in the light of the MGTX trial and histological heterogeneity of thymectomy specimens

Weis

Schalke

Ströbel

et al. 2018

Annals of the New York Academy of Sciences

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“…In our present study, we observed a dramatic involution of the thymus in 15 week old Hexb −/− FcRγ +/+ mouse. The thymus plays a crucial role in immune system homeostasis, and thymic abnormalities have been previously reported in many autoimmune diseases, such as myasthenia gravis [31], systemic sclerosis [32], in a mouse model of systemic lupus erythematosus [24], and multiple sclerosis [33]. Since autoimmunity is found also in SD, the contribution of thymus abnormalities to the pathogenesis of this disease seems plausible.…”

Section: Discussionmentioning

confidence: 89%

Thymic Alterations in GM2 Gangliosidoses Model Mice

Kanzaki

Yamaguchi

et al. 2010

PLoS ONE

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BackgroundSandhoff disease is a lysosomal storage disorder characterized by the absence of β-hexosaminidase and storage of GM2 ganglioside and related glycolipids. We have previously found that the progressive neurologic disease induced in Hexb −/− mice, an animal model for Sandhoff disease, is associated with the production of pathogenic anti-glycolipid autoantibodies.Methodology/Principal FindingsIn our current study, we report on the alterations in the thymus during the development of mild to severe progressive neurologic disease. The thymus from Hexb −/− mice of greater than 15 weeks of age showed a marked decrease in the percentage of immature CD4+/CD8+ T cells and a significantly increased number of CD4+/CD8− T cells. During involution, the levels of both apoptotic thymic cells and IgG deposits to T cells were found to have increased, whilst swollen macrophages were prominently observed, particularly in the cortex. We employed cDNA microarray analysis to monitor gene expression during the involution process and found that genes associated with the immune responses were upregulated, particularly those expressed in macrophages. CXCL13 was one of these upregulated genes and is expressed specifically in the thymus. B1 cells were also found to have increased in the thy mus. It is significant that these alterations in the thymus were reduced in FcRγ additionally disrupted Hexb −/− mice.Conclusions/SignificanceThese results suggest that the FcRγ chain may render the usually poorly immunogenic thymus into an organ prone to autoimmune responses, including the chemotaxis of B1 cells toward CXCL13.

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“…An adverse intrauterine environment seems to cause thymus dysfunction and subsequent long-term immunologic deregulation, 26 and it was significantly more likely to find incomplete thymus involution in SSc and patients with rheumatoid arthritis than in a nonautoimmune control group. 27 Several studies have demonstrated that cesarean delivery, which often is associated with stressful intrauterine conditions, is linked to shortterm consequences for the newborn infant and increased risk of asthma, allergies, and type 1 diabetes mellitus in adulthood.…”

Section: Commentmentioning

confidence: 99%

Fetal programming and systemic sclerosis

Donzelli

Carnesecchi

Amador

et al. 2015

American Journal of Obstetrics and Gynecology

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OBJECTIVE: This study investigated whether birthweight is linked to an increased risk of the development of systemic sclerosis. STUDY DESIGN:This was a multicenter case-control study with perinatal data that were obtained from 332 cases with systemic sclerosis and 243 control subjects. Birthweight was treated as a dichotomous variable (<2500 g vs !2500 g); low birthweight was defined as a weight <2500 g; small for gestational age was defined as birthweight <10th percentile for gestational age adjusted for sex. The relationship between systemic sclerosis and both low birthweight and small for gestational age was expressed with the crude (univariate analysis) and adjusted (multivariate analysis) odds ratio (OR). RESULTS:Significantly increased ORs were observed in the univariate analysis for low birthweight (OR, 2.59; 95% confidence interval [CI], 1.39e5.05) and small for gestational age (OR, 2.60; 95% CI, 1.34e5.32) subjects. Similarly increased risks were confirmed for both conditions in the multivariate analysis (OR, 3.93; 95% CI, 1.92e8.07; and OR, 2.58; 95% CI, 1.28e5.19), respectively. CONCLUSION: Low birthweight and small for gestational age at birth are risk factors for the adult onset of systemic sclerosis.

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Thymus alterations and systemic sclerosis

Cited by 29 publications

References 18 publications

Challenging the current model of early‐onset myasthenia gravis pathogenesis in the light of the MGTX trial and histological heterogeneity of thymectomy specimens

Challenging the current model of early‐onset myasthenia gravis pathogenesis in the light of the MGTX trial and histological heterogeneity of thymectomy specimens

Thymic Alterations in GM2 Gangliosidoses Model Mice

Fetal programming and systemic sclerosis

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