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Front. Immunol. | doi: 10.3389/fimmu.2019.02475

Gene-and disease-based expansion of the knowledge on inborn errors of immunity

 Lyubov E. Salnikova1, 2, 3*, Ekaterina V. Chernyshova2, Lyudmila A. Anastasevich2 and  Sergey S. Larin2
  • 1Vavilov Institute of General Genetics, Russian Academy of Sciences, Russia
  • 2Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Russia
  • 3Federal Research and Clinical Center, Federal Medical-Biological Agency, Russia

The recent report of the International Union of Immunological Societies (IUIS) has provided the categorized list of 354 inborn errors of immunity. We performed a systematic analysis of genes and diseases from the IUIS report with the use of the OMIM, ORPHANET and HPO resources. To measure phenotypic similarity we applied the Jaccard/Tanimoto (J/T) coefficient for HPO terms and top-level categories. Low J/T coefficients for HPO terms for OMIM or ORPHANET disease pairs associated with the same genes indicated high pleiotropy of these genes. Gene ORGANizer enrichment analysis demonstrated that gene sets related to HPO top-level categories were most often enriched in immune, lymphatic and corresponding body systems (for example, genes from the category ‘Cardiovascular’ were enriched in cardiovascular system). We presented available data on frequent and very frequent clinical signs and symptoms in inborn errors of immunity. With the use of DisGeNET, we generated the list of 25 IUIS/OMIM diseases with two or more relatively high score gene-disease associations, found for unrelated genes and/or for clusters of genes coding for interacting proteins. Our study showed the enrichment of gene sets related to several IUIS categories with neoplastic and autoimmune diseases from the GWAS Catalog and reported individual genes with phenotypic overlap between inborn errors of immunity and GWAS diseases/traits. We concluded that genetic background may play a role in phenotypic diversity of inborn errors of immunity.

Keywords: International Union of Immunological Societies, inborn errors of immunity, OMIM, Orphanet, human phenotype ontology, Clinical signs and symptoms, pleiotropy, Gene-disease association

Received: 31 Jul 2019; Accepted: 03 Oct 2019.

Copyright: © 2019 Salnikova, Chernyshova, Anastasevich and Larin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Mx. Lyubov E. Salnikova, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia,