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Immunohistochemical analysis of human orbital tissue in Graves’ orbitopathy

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Abstract

Purpose

Immunohistochemistry of orbital tissues offers a correlation between the microscopic changes and macroscopic clinical manifestation of Graves’ orbitopathy (GO). Summarizing the participation of different molecules will help us to understand the pathogenesis of GO.

Methods

The pertinent and current literature on immunohistochemistry of human orbital tissue in GO was reviewed using the NCBI PubMed database.

Results

33 articles comprising over 700 orbital tissue samples were included in this review. The earliest findings included the demonstration of HLA-DR and T cell (to a lesser extent B cell) markers in GO orbital tissues. Subsequent investigators further contributed by characterizing cellular infiltration, confirming the presence of HLA-DR and TSHR, as well as revealing the participation of cytokines, growth factors, adhesion molecules and miscellaneous substances. HLA-DR and TSHR are over-expressed in orbital tissues of GO patients. The inflammatory infiltration mainly comprises CD4 + T cells and macrophages. Cytokine profile suggests the importance of Th1 (especially in early active phase) and Th17 immunity in the pathogenesis of GO. Upregulation of proinflammatory/profibrotic cytokines, adhesion molecules and growth factors finally culminate in activation of orbital fibroblasts and perpetuation of orbital inflammation. The molecular status of selected parameters correlates with the clinical presentation of GO.

Conclusion

Further investigation is warranted to define precisely the role of different molecules and ongoing search for new players yet to be discovered is also important. Unfolding the molecular mechanisms behind GO will hopefully provide insights into the development of novel therapeutic strategies and optimize our clinical management of the disease.

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Acknowledgements

We thank Michael Kanitz, laboratory technician of Molecular Thyroid Research Laboratory of JGU, for offering laboratory technical support. This review contains part of the doctoral thesis of Yuanping Hai.

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  1. Yuan Ping Hai and Alan Chun Hong Lee shared co-first authorship and contributed equally to the preparation of the manuscript.

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  1. Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University Medical Center, Langenbeckstreet 1, 55131, Mainz, Germany

    Y. P. Hai, A. C. H. Lee, L. Frommer, T. Diana & G. J. Kahaly

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Work and concept were initiated by GJK; literature search and data interpretation were performed by YPH, ACHL and GJK. The manuscript was written by YPH, ACHL and GJK. LF, TD and GJK critically reviewed the manuscript.

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Correspondence to G. J. Kahaly.

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Hai, Y.P., Lee, A.C.H., Frommer, L. et al. Immunohistochemical analysis of human orbital tissue in Graves’ orbitopathy. J Endocrinol Invest 43, 123–137 (2020). https://doi.org/10.1007/s40618-019-01116-4

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