An approach to the biological significance of Major Complex polymorphism Hlistocompatibility. The model of association

Gloria Garavito, Antonio Iglesias, Eduardo Egea, Dolores Jaraquemada, Paz Martínez, Eduardo Enrique Egea

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Abstract

Objectives. To carry out an updating of the state of the art about the biological meaning of genetic system polymorphism Major Histocompatibility Complex (MHC). To review the literature related to the association of histocompatibility antigens in humans (HLA) and the susceptibility or resistance to the development of Juvenile Rheumatoid Arthritis (JRA). To present a hypothetical model to understand the genetic susceptibility to develop JRA. Data source. The bibliographic references supporting this paper were obtained through searching in the following data base: Pubmed, Ovid, Ebsco. Initially, 139 articles were found, from which 75 were selected. Information about the development of a research of our group, 'Molecular polymorphism of HLA and JRA antigens' was also included. (Colciencias code No 1215-04-280-96). Results. Juvenile rheumatoid Arthritis (JRA) is the most common disease in pediatric rheumatologic practice as well as the one with less immunogenetic studies. Contrary to the adult rheumatoid arthritis (RA), JRA has certain clinical variants which make it more interesting from the genetic point of view (phenotypes). In its pathogenesis several factors have been identified, which as a whole would explain the onset and the perpetuation of the inflammatory response affecting joints and nearby tissue as well as its imminent destruction given no control of it as is the case in other autoimmune diseases. The disease pathogenesis can be determined by alterations at the trimolecular level formed by a putative antigen: lymphocyte T receptor and the Major Histocampatibility Complex (MHC). During the last four years our group has been studying the link between JRA and the HLA DRB1* and DQB1* alleles in mestizo children of our country. Results are congruent with the findings described in the literature by different investigation groups. In the series of patients studied, we have found that the alleles HLA DRB1* 1104, HLA*0701 and HLA*1602 are linked to the susceptibility of developing JRA. Our data also show that the alleles HLA DRB1* 1501 y HLA DQB1* 0602 are clearly linked to protection. It is important to highlight that all the alleles linked to susceptibility share the Asp amino acid in position 70, and those shown as protection markers have Val in the same position. Conclusion. The information obtained from the literature and the findings in our series of Colombian patients are relevant and important because from the molecular point of view, at an antigenic presentation level, the amino acid in position 70 in the motif 67 to 73, at HLA molecule level, could activate TH1 or TH2 cells, which would be compromised in the immunopathology of this entity. Other genetic or/and environmental factors linked to these molecular characteristics expressed at the level of the HLA molecule and compromised in the antigenic response could interact and its result would be influencing the development and the expression of JRA.
Original languageEnglish
Pages (from-to)53-72
JournalSalud Uninorte
Volume16
Publication statusPublished - 1 Jan 2002

Keywords

  • Juvenile rheumatoid arthritis (JRA)
  • Major Histocompatibility Complex (MHC)

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