congresos y reuniones científicas
Phenotypic And Genetic Differences Between Adult And Paediatric Type I Autoimmune. Hepatitis: Role Of Kir2ds4-Hla Interaction
A.PODHORZER; M CUARTEROLO; H FAINBOIM; S PAZ; G THEILER; M CAPUCCHIO; S LÓPEZ; A MACHICOTE ; L FAINBOIM.
Conferencia; EASL Monothematic Conference: "Autoimmune Hepatitis; 2015
Do you want to apply for Young Investigator bursary?: YesIntroduction: We previously reported a strong association between HLA-DRB1*1301 and type 1 paediatric autoimmunehepatitis (PAH); and HLA-DR*0405 with Adult autoimmune hepatitis (AAH). We postulated that PAH and AAH mayrepresent two different clinical entities. More recently autoimmune diseases susceptibility have been also associated toHuman killer cell immunoglobulin-like receptors (KIRs)Aims: We want to establish the combined role of HLA and KIR genes in autoimmune hepatitis. In addition, we want toanalyse the differentiation stage of T cell subsets to determine if the mechanisms involved in the development of PAHand AAH are differentially dictated by innate or adaptive immunityMaterial and Methods: A total of 144 PAH patients and 86 AAH patients were compared with 273 controls. KIR and HLAA,B, and C typing was performed by polymerase chain reaction-sequence-specific oligonucleotide probing. By flowcytometry T cell differentiation stages were compared in PAH and AAH patients with paediatric and adult controlsResults: In PAH, the genomic analysis revealed a decreased frequency of KIR2DL2 and an increased frequency of thefull length KIR2DS4 (KIR2DS4-FL). In PAH-KIR2DS4FL+ subjects we detected an increased frequency of their putativeHLA-C*02, 04 and 06 ligands. In addition, PAH-KIR2DL2+ patients showed a decreased frequency of the HLA-C1 ligand.Furthermore, C2/C2 frequency within KIR2DS4FL+ homozygous/ KIR2DL2+ individuals was also increased, thus a highfrequency of these individuals had no inhibition through KIR2DL2.The combined analysis of KIR2DS4-FL and HLA-DRB1*1301 demonstrated a strong synergistic effect (OR: 36.5). InAAH, we detected a weaker increased frequency of KIR2DS4-FL, HLA association with HLA-DRB1*0405, and lack of anysynergistic effect. In contrast with PAH, AAH patients showed an expansion of the more differentiated effector T cellsConslusions: KIR2DS4-FL acting synergistically with HLA-DRB1*1301 and a diminished inhibitory effect throughKIR2DL2 appears to be involved in PAH development. In contrast AAH showed a less predominant role of KIR2DS4-FL,a lack of any synergistic effect with HLA-class II antigens, but an increased population of highly differentiated effector Tcells, which in contrast with PAH seems to endow the adaptive immunity with a predominant role in AAH pathogenesis