Human leukocyte antigens (HLA) genes are the main risk factor associated to autoimmune diseases. In predisposed individuals, surface HLA proteins of both class I and class II types present critical autoantigens to cognate CD4+ and CD8+ T lymphocytes, respectively, causing a marked inflammation of targeted self-tissues, or even their destruction. Several HLA alleles were found to predispose to autoimmune disorders and, in consequence of linkage disequilibrium characteristic of this locus, specific haplotypes were found to be associated to autoimmunity. To date, the crucial pathogenic role of HLA class I and II genes in autoimmunity has been ascribed to the peculiarity of peptide-binding groove structures, strictly depending on HLA gene polymorphisms, that determine the presentation of a large panel of self-antigens and to the presence of cognate T cells escaping thymic negative selection. Notwithstanding, it remains an unexplained question that some risk HLA alleles are shared among different autoimmune disorders often occurring as co-morbidities. Furthermore, recent studies reported a pivotal role of HLA gene expression on autoimmunity predisposition, in addition to large sequence variations. Regulatory sequence variants may affect the risk allele transcription, or modify the three-dimensional structure of locus, thus determining the prevalence of specific HLA haplotypes in autoimmunity.
The goal of this article collection is to provide new understandings on the HLA genes and haplotypes variations associated to multiple autoimmune pathologies and on the differential expression of specific risk alleles, in order to unravel the functional causes of co-morbidities. More in details, we aim to obtain new insights about the molecular mechanisms causing the differential expression of risk alleles when in heterozygosis, in different autoimmune diseases, through the analysis of expression quantitative trait loci (eQTL) at HLA locus and the identification of regulatory variants.
The submission of original research, review or mini-review, opinion, and methods articles, affording several research approaches, as genetic, molecular, immunological and functional aspects, will contribute to unravel the association between HLA and clinical relevance of autoimmunity. In particular this topic will address, but is not limited to, the following aspects of HLA and autoimmunity:
• New associations of specific HLA alleles shared by autoimmune co-morbidities
• Innovative HLA imputation methods
• Functional relationship between predisposing and protective HLA loci
• eQTL at HLA locus
• Understanding HLA gene regulation mechanisms causing differential expression of risk alleles common to different autoimmune pathologies
• Unravelling to what extent HLA genotype and/or expression contribute to explain clinical severity of autoimmune disorders
• Role of post-translational autoantigen modifications in eliciting adverse autoimmune responses
Topic Editor Dr. Carmen Gianfrani received financial support and is an advisory board member of Nemysis L.T.D Dublin, Ireland. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
Human leukocyte antigens (HLA) genes are the main risk factor associated to autoimmune diseases. In predisposed individuals, surface HLA proteins of both class I and class II types present critical autoantigens to cognate CD4+ and CD8+ T lymphocytes, respectively, causing a marked inflammation of targeted self-tissues, or even their destruction. Several HLA alleles were found to predispose to autoimmune disorders and, in consequence of linkage disequilibrium characteristic of this locus, specific haplotypes were found to be associated to autoimmunity. To date, the crucial pathogenic role of HLA class I and II genes in autoimmunity has been ascribed to the peculiarity of peptide-binding groove structures, strictly depending on HLA gene polymorphisms, that determine the presentation of a large panel of self-antigens and to the presence of cognate T cells escaping thymic negative selection. Notwithstanding, it remains an unexplained question that some risk HLA alleles are shared among different autoimmune disorders often occurring as co-morbidities. Furthermore, recent studies reported a pivotal role of HLA gene expression on autoimmunity predisposition, in addition to large sequence variations. Regulatory sequence variants may affect the risk allele transcription, or modify the three-dimensional structure of locus, thus determining the prevalence of specific HLA haplotypes in autoimmunity.
The goal of this article collection is to provide new understandings on the HLA genes and haplotypes variations associated to multiple autoimmune pathologies and on the differential expression of specific risk alleles, in order to unravel the functional causes of co-morbidities. More in details, we aim to obtain new insights about the molecular mechanisms causing the differential expression of risk alleles when in heterozygosis, in different autoimmune diseases, through the analysis of expression quantitative trait loci (eQTL) at HLA locus and the identification of regulatory variants.
The submission of original research, review or mini-review, opinion, and methods articles, affording several research approaches, as genetic, molecular, immunological and functional aspects, will contribute to unravel the association between HLA and clinical relevance of autoimmunity. In particular this topic will address, but is not limited to, the following aspects of HLA and autoimmunity:
• New associations of specific HLA alleles shared by autoimmune co-morbidities
• Innovative HLA imputation methods
• Functional relationship between predisposing and protective HLA loci
• eQTL at HLA locus
• Understanding HLA gene regulation mechanisms causing differential expression of risk alleles common to different autoimmune pathologies
• Unravelling to what extent HLA genotype and/or expression contribute to explain clinical severity of autoimmune disorders
• Role of post-translational autoantigen modifications in eliciting adverse autoimmune responses
Topic Editor Dr. Carmen Gianfrani received financial support and is an advisory board member of Nemysis L.T.D Dublin, Ireland. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
