Activating KIR and HLA Bw4 Ligands Are Associated to Decreased Susceptibility to Pemphigus Foliaceus, an Autoimmune Blistering Skin DiseaseReportar como inadecuado




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The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus PF and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hypothesis that KIR genes and their known ligands influence susceptibility to PF. We found significant negative association between activating genes and PF. The activating KIR genes may have an overlapping effect in the PF susceptibility and the presence of more than three activating genes was protective OR = 0.49, p = 0.003. A strong protective association was found for higher ratios activating-inhibitory KIR OR = 0.44, p = 0.001. KIR3DS1 and HLA-Bw4 were negatively associated to PF either isolated or combined, but higher significance was found for the presence of both together OR = 0.34, p<10−3 suggesting that the activating function is the major factor to interfere in the PF pathogenesis. HLA-Bw4 80I and 80T was decreased in patients. There is evidence that HLA-Bw480T may also be important as KIR3DS1 ligand, being the association of this pair OR = 0.07, p = 0.001 stronger than KIR3DS1-Bw480I OR = 0.31, p = 0.002. Higher levels of activating KIR signals appeared protective to PF. The activating KIR genes have been commonly reported to increase the risk for autoimmunity, but particularities of endemic PF, like the well documented influence the environmental exposure in the pathogenesis of this disease, may be the reason why activated NK cells probably protect against pemphigus foliaceus.



Autor: Danillo G. Augusto, Sara C. Lobo-Alves, Marcia F. Melo, Noemi F. Pereira, Maria Luiza Petzl-Erler

Fuente: http://plos.srce.hr/



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