Sulzbach Denardin Maiara, Bumiller-Bini Hoch Valéria, Salviano-Silva Amanda, Lobo-Alves Sara Cristina, Adelman Cipolla Gabriel, Malheiros Danielle, Augusto Danillo G, Wittig Michael, Franke Andre, Pföhler Claudia, Worm Margitta, van Beek Nina, Goebeler Matthias, Sárdy Miklós, Ibrahim Saleh, Busch Hauke, Schmidt Enno, Hundt Jennifer Elisabeth, Petzl-Erler Maria Luiza, Beate Winter Boldt Angelica
Laboratory of Human Molecular Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.
Postgraduate Program in Genetics, Department of Genetics, Federal University of Paraná (UFPR), Curitiba 81531-980, Brazil.
Life (Basel). 2023 Dec 29;14(1):60. doi: 10.3390/life14010060.
Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of were more susceptible (OR = 1.79, = 0.0038), whereas those with (OR = 0.57, = 0.0011) and homozygotes for (OR = 0.39, = 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4 T lymphocytes, using RNAseq. In these cells, we found a higher expression of , and and lower expression of and in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF.
落叶型天疱疮（PF）是一种自身免疫性皮肤水疱病，其特征是产生抗桥粒芯糖蛋白-1 IgG，在巴西存在一种地方性形式（EPF）。遗传和表观遗传因素与EPF有关，但其病因仍未完全了解。为了评估组蛋白（去）乙酰化相关基因与EPF易感性的遗传关联，我们对227例EPF患者和194例对照者评估了144个基因的785个多态性。携带[具体基因变异情况1]的个体更易患病（OR = 1.79，P = 0.0038），而携带[具体基因变异情况2]的个体（OR = 0.57，P = 0.0011）和[具体基因变异情况3]的纯合子（OR = 0.39，P = 0.0006）对EPF的易感性较低。在75例散发性PF（SPF）患者和150例对照者的德国样本中，这些变异与SPF无关，这可能反映了SPF和EPF病理生理学的差异。我们使用RNA测序进一步评估了CD4 T淋巴细胞中组蛋白（去）乙酰化相关基因的表达。在这些细胞中，我们发现与来自地方性地区的对照相比，未经治疗的活动性EPF患者中[具体基因1]、[具体基因2]和[具体基因3]的表达较高，而[具体基因4]和[具体基因5]的表达较低。所编码的蛋白质引起与免疫细胞分化和细胞死亡相关的表观遗传修饰，可能影响PF患者的免疫反应。
