Gene Map of the HLA Region, Graves’ Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation

Takehiko Sasazuki, Hidetoshi Inoko, Satoko Morishima, Yasuo Morishima

Research output: Chapter in Book/Report/Conference proceedingChapter

9 Citations (Scopus)

Abstract

The human leukocyte antigen (HLA) genomic region spanning about 4 Mb is the most gene dense and the polymorphic stretches in the human genome. A total of the 269 loci were identified, including 145 protein coding genes mostly important for immunity and 50 noncoding RNAs (ncRNAs). Biological function of these ncRNAs remains unknown, becoming hot spot in the studies of HLA-associated diseases. The genomic diversity analysis in the HLA region facilitated by next-generation sequencing will pave the way to molecular understanding of linkage disequilibrium structure, population diversity, histocompatibility in transplantation, and associations with autoimmune diseases. The 4-digit DNA genotyping of HLA for six HLA loci, HLA-A through DP, in the patients with Graves’ disease (GD) and Hashimoto thyroiditis (HT) identified six susceptible and three resistant HLA alleles. Their epistatic interactions in controlling the development of these diseases are shown. Four susceptible and one resistant HLA alleles are shared by GD and HT. Two HLA alleles associated with GD or HT control the titers of autoantibodies to thyroid antigens. All these observations led us to propose a new model for the development of GD and HT. Hematopoietic stem cell transplantation from unrelated donor (UR-HSCT) provides a natural experiment to elucidate the role of allogenic HLA molecules in immune response. Large cohort studies using HLA allele and clinical outcome data have elucidated that (1) HLA locus, allele, and haplotype mismatches between donor and patient, (2) specific amino acid substitution at specific positions of HLA molecules, and (3) ethnic background are all responsible for the immunological events related to UR-HSCT including acute graft-versus-host disease (GVHD), chronic GVHD, graft-versus-leukemia (GvL) effect, and graft failure.

Original languageEnglish
Title of host publicationAdvances in Immunology
PublisherAcademic Press Inc.
Pages175-249
Number of pages75
DOIs
Publication statusPublished - Jan 1 2016

Publication series

NameAdvances in Immunology
Volume129
ISSN (Print)0065-2776
ISSN (Electronic)1557-8445

Fingerprint

Hashimoto Disease
Hematopoietic Stem Cell Transplantation
Graves Disease
HLA Antigens
Genes
Alleles
Untranslated RNA
Graft vs Host Disease
Transplants
Unrelated Donors
Histocompatibility
Linkage Disequilibrium
Human Genome
Amino Acid Substitution
Autoantibodies
Haplotypes
Autoimmune Diseases
Immunity
Thyroid Gland
Leukemia

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Sasazuki, T., Inoko, H., Morishima, S., & Morishima, Y. (2016). Gene Map of the HLA Region, Graves’ Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation. In Advances in Immunology (pp. 175-249). (Advances in Immunology; Vol. 129). Academic Press Inc.. https://doi.org/10.1016/bs.ai.2015.08.003

Gene Map of the HLA Region, Graves’ Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation. / Sasazuki, Takehiko; Inoko, Hidetoshi; Morishima, Satoko; Morishima, Yasuo.

Advances in Immunology. Academic Press Inc., 2016. p. 175-249 (Advances in Immunology; Vol. 129).

Research output: Chapter in Book/Report/Conference proceedingChapter

Sasazuki, T, Inoko, H, Morishima, S & Morishima, Y 2016, Gene Map of the HLA Region, Graves’ Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation. in Advances in Immunology. Advances in Immunology, vol. 129, Academic Press Inc., pp. 175-249. https://doi.org/10.1016/bs.ai.2015.08.003
Sasazuki T, Inoko H, Morishima S, Morishima Y. Gene Map of the HLA Region, Graves’ Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation. In Advances in Immunology. Academic Press Inc. 2016. p. 175-249. (Advances in Immunology). https://doi.org/10.1016/bs.ai.2015.08.003
Sasazuki, Takehiko ; Inoko, Hidetoshi ; Morishima, Satoko ; Morishima, Yasuo. / Gene Map of the HLA Region, Graves’ Disease and Hashimoto Thyroiditis, and Hematopoietic Stem Cell Transplantation. Advances in Immunology. Academic Press Inc., 2016. pp. 175-249 (Advances in Immunology).
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