Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.
Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.
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DOI：
10.1371/journal.pone.0146086
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Carcassi C
中科院分区：
文献类型：
--
作者：
Littera R;Chessa L;Onali S;Figorilli F;Lai S;Secci L;La Nasa G;Caocci G;Arras M;Melis M;Cappellini S;Balestrieri C;Serra G;Conti M;Zolfino T;Casale M;Casu S;Pasetto MC;Barca L;Salustro C;Matta L;Scioscia R;Zamboni F;Faa G;Orrù S;Carcassi C
自然杀伤细胞参与自身免疫性疾病的复杂机制，但很少有研究调查它们在自身免疫性肝炎中的作用。杀伤免疫球蛋白样受体是自然杀伤细胞介导的免疫反应的关键调节因子。在 114 名诊断为 1 型自身免疫性肝炎的患者中研究了 KIR 基因频率、KIR 单倍型、KIR 配体以及 KIR 及其 HLA I 类配体的组合，并与 221 名健康对照者进行比较。将 HLA I 类和 II 类抗原频率与代表撒丁岛人口的 551 个健康无关家庭的抗原频率进行了比较。在我们的队列中，1 型自身免疫性肝炎与 HLA-B18、Cw5、DR3 单倍型密切相关。与对照组相比，患者中 KIR2DS1 激活 KIR 基因和高亲和力 HLA-C2 配体显着较高。患者的 KIR3DL1 的 HLA-Bw4 配体和 KIR2DL3 的 HLA-C1 配体频率也降低。发病年龄与 KIR2DS1 激活基因显着相关，但与 HLA-C1 或 HLA-C2 配体基团无关。激活的 KIR 基因 KIR2DS1 对 1 型自身免疫性肝炎的早期发病具有重要的预测潜力。此外，KIR-配体组合KIR3DL1/HLA-Bw4和KIR2DL3/HLA-C1的低频率与KIR2DS1的HLA-C2高亲和力配体的高频率耦合可能导致AIH-1中不需要的NK细胞自身反应性。
Natural killer cells are involved in the complex mechanisms underlying autoimmune diseases but few studies have investigated their role in autoimmune hepatitis. Killer immunoglobulin-like receptors are key regulators of natural killer cell-mediated immune responses. KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 114 patients diagnosed with type 1 autoimmune hepatitis and compared with a group of 221 healthy controls. HLA Class I and Class II antigen frequencies were compared to those of 551 healthy unrelated families representative of the Sardinian population. In our cohort, type 1 autoimmune hepatitis was strongly associated with the HLA-B18, Cw5, DR3 haplotype. The KIR2DS1 activating KIR gene and the high affinity HLA-C2 ligands were significantly higher in patients compared to controls. Patients also had a reduced frequency of HLA-Bw4 ligands for KIR3DL1 and HLA-C1 ligands for KIR2DL3. Age at onset was significantly associated with the KIR2DS1 activating gene but not with HLA-C1 or HLA-C2 ligand groups. The activating KIR gene KIR2DS1 resulted to have an important predictive potential for early onset of type 1 autoimmune hepatitis. Additionally, the low frequency of the KIR-ligand combinations KIR3DL1/HLA-Bw4 and KIR2DL3/HLA-C1 coupled to the high frequency of the HLA-C2 high affinity ligands for KIR2DS1 could contribute to unwanted NK cell autoreactivity in AIH-1.