Просмотр кода страницы Allotype (immunology)

[[Image:AntibodyChains.svg|thumb|The allotype affects the constant region (labeled CL and CH1-3 in the diagram.)]]
The word '''allotype''' comes from two Greek roots, ''allo'' meaning 'other or differing from the norm' and ''typos'' meaning 'mark'.<ref>{{Cite web|title=Pathology, Microbiology and Immunology | publisher = University of South Carolina School of Medicine |url=https://sc.edu/study/colleges_schools/medicine/education/basic_science_departments/pathology_microbiology_and_immunology/index.php|access-date=2020-09-06 }}</ref> In [[immunology]], allotype is an [[Antibody|immunoglobulin]] variation (in addition to [[Isotype (immunology)|isotypic]] variation) that can be found among [[Antibody|antibody classes]] and is manifested by heterogeneity of [[Antibody|immunoglobulins]] present in a single [[vertebrate]] species. The structure of [[Antibody|immunoglobulin polypeptide chain]] is dictated and controlled by number of genes encoded in the [[Germline|germ line]].<ref>{{cite book | vauthors = Mage R, Lieberman R, Potter M, Terry WD | chapter = Immunoglobulin Allotypes | title = The Antigens | date = January 1973 | pages = 299–376 | publisher = Academic Press | doi = 10.1016/b978-0-12-635501-7.50010-1 | isbn = 978-0-12-635501-7 }}</ref> However, these [[gene]]s, as it was discovered by serologic and chemical methods, could be highly [[Polymorphism (biology)|polymorphic]]. This [[Polymorphism (biology)|polymorphism]] is subsequently projected to the overall [[amino acid]] structure of [[Antibody|antibody chains]]. [[Polymorphism (biology)|Polymorphic]] [[epitope]]s can be present on [[Constant region|immunoglobulin constant regions]] on both heavy and light chains, differing between individuals or ethnic groups and in some cases may pose as [[Immunogenicity|immunogenic determinants]].<ref>{{cite journal | vauthors = de Lange GG | title = Polymorphisms of human immunoglobulins: Gm, Am, Em and Km allotypes | journal = Experimental and Clinical Immunogenetics | volume = 6 | issue = 1 | pages = 7–17 | date = 1989 | pmid = 2698222 }}</ref> Exposure of individuals to a non-self allotype might elicit an anti- allotype response and became cause of problems for example in a patient after transfusion of blood<ref name=":0">{{cite journal | vauthors = Jefferis R, Lefranc MP | title = Human immunoglobulin allotypes: possible implications for immunogenicity | journal = mAbs | volume = 1 | issue = 4 | pages = 332–8 | date = August 2009 | pmid = 20073133 | pmc = 2726606 | doi = 10.4161/mabs.1.4.9122 }}</ref> or in a pregnant woman.<ref>{{cite journal | vauthors = Fudenberg HH, Fudenberg BR | title = Antibody to Hereditary Human Gamma-Globulin (GM) Factor Resulting from Maternal-Fetal Incompatibility | journal = Science | volume = 145 | issue = 3628 | pages = 170–1 | date = July 1964 | pmid = 14171557 | doi = 10.1126/science.145.3628.170 | bibcode = 1964Sci...145..170F | s2cid = 42336232 }}</ref> However, it is important to mention that not all variations in [[Antibody|immunoglobulin]] amino acid sequence pose as a determinant responsible for immune response. Some of these allotypic determinants may be present at places that are not well exposed and therefore can be hardly serologically discriminated. In other cases, variation in one isotype can be compensated by the presence of this determinant on another antibody [[Isotype (immunology)|isotype]] in one individual.<ref>{{cite journal | vauthors = Vidarsson G, Dekkers G, Rispens T | title = IgG subclasses and allotypes: from structure to effector functions | language = English | journal = Frontiers in Immunology | volume = 5 | pages = 520 | date = 2014 | pmid = 25368619 | pmc = 4202688 | doi = 10.3389/fimmu.2014.00520 | doi-access = free }}</ref> This means that divergent allotype of heavy chain of IgG [[antibody]] may be balanced by presence of this allotype on heavy chain of for example IgA [[antibody]] and therefore is called isoallotypic variant. Especially large number of [[Polymorphism (biology)|polymorphisms]] were discovered in IgG [[antibody]] subclasses. Which were practically used in forensic medicine and in paternity testing, before replaced by modern day [[DNA profiling|DNA fingerprinting]].<ref name=":0" />

== Definition and organisation of allotypes in humans ==
Human allotypes nomenclature was first described in alphabetical system and further systematized in numerical system, but both could be found in the literature.<ref>{{cite journal |date=1974 | author = International Union of Immunological Sciences | title = Recommendations for the Nomenclature of Human Immunoglobins |journal=European Journal of Biochemistry |volume=45 |issue=1 |pages=5–6 |doi=10.1111/j.1432-1033.1974.tb03522.x |doi-access=free }}</ref><ref>{{Cite journal |date=1976 |title=Review of the Notation for the Allotypic and Related Markers of Human Immunoglobulins |journal= International Journal of Immunogenetics |volume=3 |issue=5 |pages=357–362 |doi=10.1111/j.1744-313X.1976.tb00595.x |s2cid=32562449 }}</ref> For example, allotype expressed on constant region of heavy chain on IgG are designated by Gm which stands for ‘genetic marker ‘ together with IgG subclass (IgG1 àG1m, IgG2 àG2m) and the allotype number or letter [ G1m1/ G1m (a) ]. [[Polymorphism (biology)|Polymorphisms]] within IgA are denoted in the same way as A2m (eg. A2m1/2) and kappa light chains constant region [[Polymorphism (biology)|polymorphisms]] as Km (eg. Km1). Despite the fact, that there are multiple known lambda chain [[Isotype (immunology)|isotypes]], there have not been reported any lambda chain serological [[Polymorphism (biology)|polymorphisms]].<ref>{{cite journal | vauthors = Ghanem N, Dariavach P, Bensmana M, Chibani J, Lefranc G, Lefranc MP | title = Polymorphism of immunoglobulin lambda constant region genes in populations from France, Lebanon and Tunisia | journal = Experimental and Clinical Immunogenetics | volume = 5 | issue = 4 | pages = 186–95 | date = 1988 | pmid = 2908491 }}</ref>

All these before mentioned allotypes are expressed on constant regions of the [[Antibody|immunoglobulin]]. [[Gene]]s responsible for encoding structure of constant regions of heavy chains are closely linked and therefore inherited together as one [[haplotype]] with low number of [[Chromosomal crossover|crossovers]]. Although some [[Chromosomal crossover|crossovers]] did occur during [[human evolution]] resulting in the creation of current populations characteristic [[haplotype]]s and importance of allotype system in population studies.<ref>{{Cite web|title=IMGT Repertoire (IG and TR)|url=http://www.imgt.org/IMGTrepertoire/Proteins/allotypes/human/IGH/IGHC/G1m_allotypes.html|access-date=2020-09-06|work=International ImMunoGeneTics Information System (IMGT)|archive-date=2021-11-01|archive-url=https://web.archive.org/web/20211101184725/http://www.imgt.org/IMGTrepertoire/Proteins/allotypes/human/IGH/IGHC/G1m_allotypes.html|url-status=dead}}</ref><ref>{{cite book | vauthors = Lefranc MP, Lefranc G | title = Immunogenetics | chapter = Human Gm, Km, and Am allotypes and their molecular characterization: a remarkable demonstration of polymorphism | series = Methods in Molecular Biology | volume = 882 | pages = 635–80 | date = 2012 | pmid = 22665258 | doi = 10.1007/978-1-61779-842-9_34 | isbn = 978-1-61779-841-2 }}</ref>

== Implications for monoclonal antibody therapy ==
[[Antibody]] allotypes came back to spotlight due to development and use of therapies based on [[Monoclonal antibody|monoclonal antibodies]]. These [[Recombinant DNA|recombinant]] human [[glycoprotein]]s and [[protein]]s are now well established in clinical practise, but sometimes leads to adverse effects such as generation of antitherapeutic [[Antibody|antibodies]] that negates therapy or even cause severe reactions to the therapy. This reaction may be attributed to differences between therapeutics itself or may arise between same therapeutics produced by different companies or even between different lots produced by the same company. To prevent production of such antitherapeutic [[Antibody|antibodies]], ideally, all clinical used [[protein]]s and [[glycoprotein]]s should poses same allotype as natural patient’s product, this way the presence of ‘altered self‘ which poses a potential target for [[immune system]], is limited. Whilst many parameters connected to developing and manufacturing process that might predispose [[Monoclonal antibody|monoclonal antibodies]] to cause [[immune response]] are well known and appropriate steps are taken to monitor and control these unwanted effects, complications linked with administration of [[Monoclonal antibody|monoclonal antibodies]] to genetically diverse human population are less well described. Humans exhibit abundance of [[genotype]]s and [[phenotype]]s, however all currently licensed IgG therapeutic [[Antibody|immunoglobulins]] are developed as single allotypic/ [[Polymorphism (biology)|polymorphic]] form. Patients that are homozygous for alternative [[phenotype]] are therefore at higher risk of developing potential [[immune response]] to the therapy.<ref name=":0" />

== See also ==
* [[Allotype (disambiguation)]]
* [[Idiotype]]
* [[Isotype (immunology)|Isotype]]

== References ==
{{reflist}}

== External links ==
* {{MeshName|Immunoglobulin+allotypes}}


{{Immune system}}

[[Category:Genetics]]
[[Category:Transplantation medicine]]