Sağlıklı, hiperplazik ve adenomatöz paratiroit dokularında minör ve majör histokompatibilite antijenlerinin ekspresyon miktarlarının karşılaştırılması / Comparison of the expression patterns of minor and major histocompatibility antigens in healthy, hyperplasic and adenomatous parathyroid tissues

Abstract

As we learn more about how immune response occurs, it is becoming clear that the characteristics of the tissue can be important as immune cells determines the initiation and progression of an immune response. A formal definition of immunogenicity can be stated as "the ability of a molecule to provoke an immune response or the strength of an immune response". Tissue-specific immunogenicity can be characterized by the determination of Major Histocompatibility Complex and Minor Histocompatibility Antigens as well. The immunogenetic studies of histocompatibility antigens categorized into two groups; major and minor histocompatibility antigens. Human major histocompatibility antigens are known as "human leukocyte antigen" system. The human leukocyte antigen complex is located within the short arm of human chromosome 6 and contains more than 200 genes, has important activities in biology and medicine with the gene regions of diverse function. The major role in medicine is the donor selection in organ and stem cell transplantation. The coordination between innate and adaptive immunity eliminates the survival of organ transplantations as well as parathyroid transplantations. In allorecognition, antigen presenting cells activated by peptide/human leukocyte antigen (HLA) complex and thus changing its course through lymph nodes where T cells reside. Once the recipient antigen presenting cells recognize donor tissue, this leads to activation and migration of T cells where they promote rejection. In solid organ transplantation, cultured tissue cells were presumed as passenger-leukocyte free which ensures prolonged graft survival. With the aim of understanding and characterization of parathyroid gland immunogenicity; the both protein and gene expression patterns of major histocompatibility antigens class I; HLA-A, HLA-B, HLA-C and class II; HLA-DR, HLA-DP, HLA-DQα1, HLA-DQα2 regions were compared in cultured parathyroid cells that derived from healthy, hyperplasic and adenomatous parathyroid tissues. In addition, autosomal restricted minor histocompatibility antigen SP110 protein expression investigated healthy, hyperplasic and adenomatous parathyroid tissues. As a result, HLA-A protein expression remained the same during culture but mRNA expression decreased. HLA-B protein and mRNA expression decreased only in hyperplasia tissues. HLA-C showed weak/no protein expression for both tissues. In addition, cultured parathyroid tissues are still potential targets for class II-restricted allorecognition even during the culture. Therefore, -DQα2 and -DR protein expression was found higher. Besides, parathyroid tissues showed SP110 peptide expression level as follows not detected or moderate in healthy, hyperplasic and adenomatous parathyroid tissues respectively. In conclusion, HLA class I expression patterns was different at every stage. The change in mRNA levels and protein levels was not correlated in different parathyroid tissues and even during culture. Another outcome that the concordance between HLA-DQ and -DR indicates a possible linkage in rejection/poor graft survival of parathyroid tissue transplantation via allorecognition. This mainly due to the regulation control at different levels between gene and its protein as well. The biochemical diversity of proteins means that the individual correlation levels with the associated mRNA varies in parathyroid tissues. Parathyroid tissue should be evaluated in detail with this expression patterns of HLA class I and II for allorecognition prior to transplantation. Current studies showed autosomal restricted minor histocompatibility antigen SP110 peptide was found to recognize HLA-A*03 allele and significantly induces macrophage activation. In future studies, SP110 positivity of parathyroid tissues evaluates for macrophage activation via in vitro cell culture system.