HLA Class I Polymorphisms Influencing Both Peptide Binding and KIR Interactions Are Associated with Remission among Children with Atopic Dermatitis: A Longitudinal Study.

Autor:	Margolis DJ; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, PA; margo@pennmedicine.upenn.edu monosd@email.chop.edu.; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Mitra N; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, PA., Kim BS; Center for the Study of Itch and Sensory Disorders, Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO., Duke JL; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Berna RA; Department of Dermatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA., Hoffstad OJ; Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, Philadelphia, PA., Wasserman JR; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Ferriola DA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Mosbruger TL; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA., Wubbenhorst BS; Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA.; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and., Nathanson KL; Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania Philadelphia, PA.; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and., Monos DS; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA; margo@pennmedicine.upenn.edu monosd@email.chop.edu.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 May 01; Vol. 206 (9), pp. 2038-2044. Date of Electronic Publication: 2021 Apr 16.
DOI:	10.4049/jimmunol.2001252
Abstrakt:	Atopic dermatitis (AD) is a disease of immune dysregulation and skin barrier dysfunction with a relapsing, remitting course and has been associated with several different genetic risk variants. HLA represent a highly variable set of genes that code for cell surface protein molecules involved in the Ag-specific immune response, including the regulation or functioning of T cells, NK cells, and APCs. The purpose of this study was to evaluate associations between HLA class I polymorphisms and the progression of AD over time. We evaluated the associations of AD symptoms and HLA class I polymorphisms based on high-resolution two-field typing in a longitudinal cohort of children with AD (up to 10 y of follow-up). Seven hundred and ninety-two children were evaluated every 6 mo, resulting in 12,752 AD evaluations. Using generalized estimating equations and corrected p values, B*44:02 was found to be associated with AD remission (1.83 [1.35, 2.47]; p = 0.0015). The HLA-B residues at position 116 (d-aspartate) and 80 (T-threonine) were associated with remission (1.42 [1.13, 1.76], p = 0.003; corrected p = 0.028) and (1.45 [1.17, 1.80], p = 0.0008; corrected p = 0.0024), respectively. B80T is a killer-cell Ig-like receptor (KIR) site. Our findings reveal that two axes of immune response (T cell and NK cell) may influence disease progression. Identifying binding pocket changes in addition to other factors (e.g., allergens) that increase the risk or severity of AD can improve our understanding of the immunologic mechanisms associated with AD and may lead to personalized therapies for improving patient care. (Copyright © 2021 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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