KIR molecules: recent patents of interest for the diagnosis and treatment of several autoimmune diseases, chronic inflammation, and B-cell malignancies.
Valli De Re, Laura Caggiari, Mariangela De Zorzi, Giuseppe Toffoli
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引用次数: 6
Abstract
There has been rapidly increasing interest in innate immunity in recent years. Natural killer (NK) cells are cytotoxic lymphocytes that constitute a major component of the innate immune system. NK cells are mainly modulated through different receptors and cytokines. The killer immunoglobulin-like receptors (KIRs) represent the largest category of NK cell receptors. KIR function is mainly regulated by binding both classical MHC I (human leukocyte antigen, HLA A, B and C) and also non-classical MHC. Some KIRs are specific to certain HLA subtypes. Questions about how the NK cells sense self-antigen, infection, and altered cells, and how a protective immune response can be induced are being answered at the molecular level. Research has revealed the central role of innate immunity in the pathogenesis of many autoimmune and inflammatory diseases, as well as B-cell malignancies, with the emergence of recent developments for KIR characterization, disease monitoring, and treatment. In this paper, we report three recent patents focused on KIR applications: the first one is targeted at the determination of the complex KIR haplotypes by using next generation sequencing; the second patent represents a practical approach for genotyping and treatment of the main KIR-related autoimmune and chronic inflammatory diseases; and the last patent describes the possible contributions of KIR to promising combination immunotherapies.
近年来,人们对先天免疫的兴趣迅速增加。自然杀伤(NK)细胞是细胞毒性淋巴细胞,构成先天免疫系统的主要组成部分。NK细胞主要受不同受体和细胞因子的调控。杀伤免疫球蛋白样受体(KIRs)是NK细胞受体中最大的一类。KIR功能主要通过结合经典MHC I(人白细胞抗原,HLA A, B和C)和非经典MHC来调节。一些kir是特定于某些HLA亚型的。关于NK细胞如何感知自身抗原、感染和变异细胞,以及如何诱导保护性免疫反应的问题正在分子水平上得到解答。随着KIR表征、疾病监测和治疗的最新进展,研究揭示了先天免疫在许多自身免疫性和炎症性疾病以及b细胞恶性肿瘤发病机制中的核心作用。在本文中,我们报告了最近三项专注于KIR应用的专利:第一项专利是利用下一代测序技术确定复杂的KIR单倍型;第二项专利代表了一种用于基因分型和治疗主要与kirr相关的自身免疫性和慢性炎症性疾病的实用方法;最后一项专利描述了KIR对有前景的联合免疫疗法的可能贡献。