PILRA, also known as paired immunoglobulin-like type 2 receptor alpha, is a cell-surface inhibitory receptor. It plays a role in regulating immune responses, being involved in both innate and adaptive immunity. It is part of pathways related to inflammation, cytokine interactions, and may be associated with processes like cell-mediated amyloid-β clearance [3,6]. Genetic models can be valuable for studying PILRA to understand its functions in more detail.

In Alzheimer's disease (AD), PILRA polymorphism (rs1859788 A > G) may be a protective variant. There are negative interactions between the PILRA-A allele and GM17 as well as APOE risk variants regarding AD risk. In a replication cohort, a joint effect of PILRA and PILRA×GM17/17 was observed for AD risk. Also, the PILRA G78R variant correlates with higher HSV-1-specific IgG titers in AD patients, and the genetically predicted level of PILRA in plasma is causally associated with AD [1,4,5].

In atrial fibrillation (AF), PILRA expression is elevated, and it is closely related to the infiltration of multiple immune cell types, such as neutrophils, macrophages, and T cells, suggesting it may be a novel intervention target for AF [2].

In pan-cancer studies, PILRA is significantly dysregulated and mutated, impacts patient prognosis, is correlated with tumor-infiltrating immune cells and immunotherapy biomarkers, and may be involved in regulating immune response and metabolic processes [7].

In conclusion, PILRA is crucial in regulating immune responses. Through model-based research, its role in diseases like Alzheimer's disease, atrial fibrillation, and cancer has been revealed. These findings contribute to understanding the pathogenesis of these diseases and potentially identifying new therapeutic targets.

References:

1. Lopatko Lindman, Karin, Jonsson, Caroline, Weidung, Bodil, Elgh, Fredrik, Lövheim, Hugo. 2022. PILRA polymorphism modifies the effect of APOE4 and GM17 on Alzheimer's disease risk. In Scientific reports, 12, 13264. doi:10.1038/s41598-022-17058-6. https://pubmed.ncbi.nlm.nih.gov/35918447/

2. Shi, Weihua, Li, Xiaoli, Su, Yongxing, Zhong, Guoqiang, Jiang, Zhiyuan. 2023. PILRA is associated with immune cells infiltration in atrial fibrillation based on bioinformatics and experiment validation. In Frontiers in cardiovascular medicine, 10, 1082015. doi:10.3389/fcvm.2023.1082015. https://pubmed.ncbi.nlm.nih.gov/37396579/

3. Hampel, Harald, Caraci, Filippo, Cuello, A Claudio, Vergallo, Andrea, Lista, Simone. 2020. A Path Toward Precision Medicine for Neuroinflammatory Mechanisms in Alzheimer's Disease. In Frontiers in immunology, 11, 456. doi:10.3389/fimmu.2020.00456. https://pubmed.ncbi.nlm.nih.gov/32296418/

4. Agostini, Simone, Costa, Andrea Saul, Mancuso, Roberta, Nemni, Raffaello, Clerici, Mario. 2019. The PILRA G78R Variant Correlates with Higher HSV-1-Specific IgG Titers in Alzheimer's Disease. In Cellular and molecular neurobiology, 39, 1217-1221. doi:10.1007/s10571-019-00712-5. https://pubmed.ncbi.nlm.nih.gov/31297637/

5. Zhan, Hui, Cammann, Davis, Cummings, Jeffrey L, Dong, Xianjun, Chen, Jingchun. 2025. Biomarker identification for Alzheimer's disease through integration of comprehensive Mendelian randomization and proteomics data. In Journal of translational medicine, 23, 278. doi:10.1186/s12967-025-06317-5. https://pubmed.ncbi.nlm.nih.gov/40050982/

6. Li, Yihan, Laws, Simon M, Miles, Luke A, Masters, Colin L, Gu, Ben J. 2021. Genomics of Alzheimer's disease implicates the innate and adaptive immune systems. In Cellular and molecular life sciences : CMLS, 78, 7397-7426. doi:10.1007/s00018-021-03986-5. https://pubmed.ncbi.nlm.nih.gov/34708251/

7. Li, Qiao, Yang, Zhirong, He, Xiaoyan, Yang, Xin. 2023. Comprehensive analysis of PILRΑ's association with the prognosis, tumor immune infiltration, and immunotherapy in pan-cancer. In Scientific reports, 13, 14334. doi:10.1038/s41598-023-41649-6. https://pubmed.ncbi.nlm.nih.gov/37652967/