Activating KIR and HLA Bw4 ligands are associated to decreased susceptibility to pemphigus foliaceus, an autoimmune blistering skin disease.
Activating KIR and HLA Bw4 ligands are associated to decreased susceptibility to pemphigus foliaceus, an autoimmune blistering skin disease.
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DOI：
10.1371/journal.pone.0039991
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Petzl-Erler ML
中科院分区：
文献类型：
--
作者：
Augusto DG;Lobo-Alves SC;Melo MF;Pereira NF;Petzl-Erler ML
KIR基因及其HLA I类配体迄今尚未在落叶型天疱疮（PF）和相关自身免疫性疾病（如寻常型天疱疮）中进行研究。我们用PCR-SSP对233例患者和204例对照进行了KIR基因分型。采用LABType SSO试剂盒进行HLA分型。我们估计了比值比，95%的置信区间，并进行逻辑回归分析，以检验假设，KIR基因及其已知的配体影响PF的易感性。我们发现激活基因和PF之间显着的负相关。激活KIR基因可能有重叠的影响PF的易感性和存在三个以上的激活基因是保护性的（OR = 0.49，p = 0.003）。 发现较高比率的活化/抑制KIR具有较强的保护性相关性（OR = 0.44，p = 0.001）。 KIR 3DS 1和HLA-Bw 4与PF单独或联合均呈负相关，但两者同时存在的显著性更高（OR = 0.34，p<10−3），表明激活功能是干扰PF发病的主要因素。 HLA-Bw 4（80 I和80 T）在患者中降低。有证据表明，HLA-Bw 4（80 T）也可能是重要的KIR 3DS 1配体，这对（OR = 0.07，p = 0.001）的关联强于KIR 3DS 1-Bw 4（80 I）（OR = 0.31，p = 0.002）。 较高水平的激活KIR信号似乎保护PF。激活KIR基因已被普遍报道，以增加自身免疫的风险，但地方性PF的特殊性，如有充分证据的影响，环境暴露在这种疾病的发病机制，可能是激活的NK细胞可能保护对落叶型天疱疮的原因。
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-Bw4(80T) may also be important as KIR3DS1 ligand, being the association of this pair (OR = 0.07, p = 0.001) stronger than KIR3DS1-Bw4(80I) (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.
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DOI：
10.4049/jimmunol.1001951
发表时间：
2010-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Moesta AK;Graef T;Abi-Rached L;Older Aguilar AM;Guethlein LA;Parham P
通讯作者：
Parham P
影响因子：
4.4
作者：
Foley, Bree;De Santis, Dianne;Witt, Campbell
通讯作者：
Witt, Campbell
影响因子：
3.6
作者：
Garcia-Leon, Juan A.;Pinto-Medel, Maria J.;Leyva-Fernandez, Laura
通讯作者：
Leyva-Fernandez, Laura
DOI：
10.1111/j.1087-0024.2004.00833.x
发表时间：
2004-01-01
影响因子：
--
作者：
Aoki, V;Millikan, RC;Diaz, LA
通讯作者：
Diaz, LA
影响因子：
3.2
作者：
Augusto, D. G.;Zehnder-Alves, L.;Pincerati, M. R.;Martin, M. P.;Carrington, M.;Petzl-Erler, Maria Luiza
通讯作者：
Petzl-Erler, Maria Luiza