MICA-129Met/Val作为特发性肺纤维化的治疗指南针：预后与抗纤维化获益
MICA-129Met/Val as a therapeutic compass in idiopathic pulmonary fibrosis: prognosis and antifibrotic benefit.
摘要(中文译文)
特发性肺纤维化（IPF）是一种进行性间质性肺病，以异常伤口愈合、免疫失调、异质性病程轨迹和不良预后为特征。目前仅有两种抗纤维化药物获批用于延缓疾病进展，但治疗获益的个体间差异在很大程度上仍无法解释。在IPF中，改变的肺部微环境中NK细胞活性受损可能阻碍应激细胞或衰老细胞的清除，从而促进纤维化。MHC-I类链相关基因A（MICA）编码NKG2D受体的应激诱导配体，该受体表达于NK细胞和CD8 T细胞，对免疫监视至关重要。我们分析了129例撒丁岛IPF患者的临床和遗传数据，这些患者接受了MICA基因分型，并按抗纤维化治疗分层（吡非尼酮、无治疗和转换治疗者）。采用多因素Cox模型校正人口学和免疫遗传学变量，评估基因型与纵向肺功能、总生存期（OS）及治疗特异性结局的关系。MICA基因型频率在各治疗组间相当。在吡非尼酮治疗患者中，Val/Val基因型与Met/Met和Met/Val相比，48个月OS显著降低（p = 0.005）。在尼达尼布治疗患者中未观察到统计学显著的关联。校正后，Val/Val仍是吡非尼酮组死亡的独立预测因素（p = 0.01），与MICA背景无关。MICA-129 Val/Val基因型可能是与吡非尼酮治疗IPF患者较差结局相关的候选免疫遗传学标志物，凸显了免疫遗传背景对抗纤维化反应的影响。尽管亚组样本量限制了精确性，但该关联的一致性和机制合理性支持将MICA基因分型纳入未来随机试验，以完善IPF的个体化治疗策略。
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by aberrant wound healing, immune dysregulation, heterogeneous trajectories, and poor prognosis. Only two antifibrotic agents, and , are currently approved to slow disease progression, yet inter-individual variability in treatment benefit remains largely unexplained. In IPF, impaired NK-cell activity within the altered lung microenvironment may hinder removal of stressed or senescent cells, promoting fibrosis. The MHC-class I chain-related gene A () encodes a stress-induced ligand of the NKG2D receptor on NK and CD8 T cells, crucial for immune surveillance. We analyzed clinical and genetic data from 129 Sardinian IPF patients genotyped for MICA and stratified by antifibrotic therapy (, no therapy, and switchers). Genotypes were assessed in relation to longitudinal lung function, overall survival (OS), and treatment-specific outcomes using multivariate Cox models adjusted for demographic and immunogenetic variables. genotype frequencies were comparable across treatment groups. In -treated patients, the Val/Val genotype was associated with significantly reduced 48-month OS versus Met/Met and Met/Val (p = 0.005). No statistically significant association was observed among pirfenidone-treated patients. After adjustment, Val/Val remained an independent predictor of mortality in the group (p = 0.01), irrespective of background. The -129 Val/Val genotype may represent a candidate immunogenetic marker associated with poorer outcome in -treated patients with IPF, underscoring the influence of immune-genetic context on antifibrotic response. Although subgroup sizes limit precision, the consistency and mechanistic plausibility of the association support integrating genotyping into future randomized trials to refine personalized therapeutic strategies in IPF.
如何引用
AMA
Stefano Mocci, Caterina Mereu, Roberto Littera, Silvia Deidda, Federica Cannas, Michela Lorrai, et al. MICA-129Met/Val as a therapeutic compass in idiopathic pulmonary fibrosis: prognosis and antifibrotic benefit.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1722213.
APA
Stefano Mocci, Caterina Mereu, Roberto Littera, Silvia Deidda, Federica Cannas, Michela Lorrai, et al (2026). MICA-129Met/Val as a therapeutic compass in idiopathic pulmonary fibrosis: prognosis and antifibrotic benefit.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1722213
GB/T 7714
Stefano Mocci, Caterina Mereu, Roberto Littera, Silvia Deidda, Federica Cannas, Michela Lorrai, et al. MICA-129Met/Val as a therapeutic compass in idiopathic pulmonary fibrosis: prognosis and antifibrotic benefit.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1722213.
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