title: Soluble monomers, dimers and HLA-G-expressing extracellular vesicles: the three dimensions of structural complexity to use HLA-G as a clinical biomarker.
abstract: The HLA-G molecule belongs to the family of nonclassical human leukocyte antigen (HLA) class I. At variance to classical HLA class I, HLA-G displays (i) a low number of nucleotide variations within the coding region, (ii) a high structural diversity, (iii) a restricted peptide repertoire, (iv) a limited tissue distribution and (v) strong immune-suppressive properties. The physiological HLA-G surface expression is restricted to the maternal-fetal interface and to immune-privileged adult tissues. Soluble forms of HLA-G (sHLA-G) are detectable in various body fluids. Cellular activation and pathological processes are associated with an aberrant or a neo-expression of HLA-G/sHLA-G. Functionally, HLA-G and its secreted forms are considered to be key players in the induction of short- and long-term tolerance. Thus, its unique expression profile and tolerance-inducing functions render HLA-G/sHLA-G an attractive biomarker to monitor the systemic health/disease status and disease activity/progression for clinical approaches in disease management and treatments. Here, we place emphasis on (i) the current status of the tolerance-inducing functions by HLA-G/sHLA-G, (ii) the current complexity to implement this molecule as a meaningful clinical biomarker regarding the three dimensions of structural diversity (monomers, dimers and HLA-G-expressing extracellular vesicles) with its functional implications, and (iii) novel and future approaches to detect and quantify sHLA-G structures and functions.
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.|Laboratory of Immunogenetics and Histocompatibility (LIGH), Federal University of Paraná, Genetics Department, Curitiba, Brazil.|Ministry of Education of Brazil, Capes Foundation, Brasília, Brazil.
authors.forename: F da Silva
authors.initials: Fda S
authors.lastname: Nardi
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.|Department of Gynecology and Obstetrics, University of Duisburg-Essen, Essen, Germany.
authors.forename: L
authors.initials: L
authors.lastname: König
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wagner
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Giebel
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.|Ministry of Education of Brazil, Capes Foundation, Brasília, Brazil.
authors.forename: L F
authors.initials: LF
authors.lastname: Santos Manvailer
authors.affiliation: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Rebmann
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000737:chemistry / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000276:immunology; D005786:Gene Expression Regulation; D059951:HLA-G Antigens / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007154:Immune System Diseases / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance; D010920:Placenta / Q000276:immunology; D011110:Polymorphism, Genetic; D011247:Pregnancy; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D055503:Protein Multimerization; D012995:Solubility
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens; D020033:Protein Isoforms
keywords: HLA-G; HLA-G monomers; HLA-G-expressing EVs; KIR2DL4; LILRB1; LILRB2; extracellular vesicles; sHLA-G