免疫性不孕和流產病患的蛋白質體學：基於質譜的蛋白質定量分析來鑑定生物指標

Proteomics among Immune Infertility and Miscarriage Patients: Identification of Biomarkers by Mass Spectrometry-based Protein Quantification Analysis

目的：本研究旨在探討並比較免疫性不孕與流產女性的血漿蛋白質體表現，目標為鑑別出與免疫與代謝調控相關的差異性表現生物指標。
方法：血漿檢體來自於納入的11位女性受試者，包括8位免疫性不孕或流產患者及3位健康對照。利用質譜進行定量蛋白質體分析，以篩選差異性蛋白表現。依據預設標準（蛋白質表現倍數> 1.5或<0.67，p < 0.05，CV < 30%）鑑定，並進行次族群分析。
結果：各組別間觀察到明顯的蛋白質體差異表現。Endoplasmic reticulum aminopeptidase 2（ERAP2）在不孕症患者中顯著上升，顯示其可能參與免疫失調，並具潛力作為風險生物標記。相對地，β-arrestin-1在流產個案中一致性下降，可能於維持妊娠中扮演保護角色。其他與免疫調控、代謝與補體路徑相關的蛋白，如Nicotinamide phosphoribosyltransferase（NAMPT）、All-trans-retinol dehydrogenase（ADH4）及Complement factor H-related protein 2（CFHR2）、Translin及Peptidyl-prolyl cis-trans isomerase FKBP1A等，也呈現表現量差異，支持不孕症涉及多重機轉。
結論：本研究顯示特定血漿蛋白，特別是ERAP2與β-arrestin-1，可能可作為生殖功能失調的生物指標。儘管樣本數較少且治療時間有所差異，此初步結果可提供免疫性不孕與流產之蛋白質體學有價值的線索。未來仍需進行具功能性驗證之大型樣本數研究，以確認本研究發現並探討其臨床應用潛力。

Objective: This study aimed to explore and compare the plasma proteomic profiles of women with immune infertility and miscarriage, with the goal of identifying differentially expressed biomarkers related to immune and metabolic regulation.
Methods: Plasma samples were collected from 11 female participants, including 8 patients with immune infertility or miscarriage, and 3 healthy controls. mass spectrometry-based quantitative proteomics was performed to profile protein expression. Differentially expressed proteins were identified using predefined cut-offs (abundance ratio >1.5 or <0.67, p-value < 0.05, CV < 30%) and further analyzed by subgroup comparison.
Results: A distinct proteomic imbalance was observed across groups. Endoplasmic reticulum aminopeptidase 2 (ERAP2) was markedly upregulated in patients with reproductive disorders, suggesting its involvement in immune dysregulation and its potential as a risk biomarker. Conversely,β-arrestin-1 was consistently downregulated in miscarriage cases, indicating a possible protective role in maintaining pregnancy. Other proteins related to immune regulation, metabolic and complement pathways, such as Nicotinamide phosphoribosyltransferase (NAMPT), All-trans-retinol dehydrogenase (ADH4), Complement factor H-related protein 2 (CFHR2), Translin, and Peptidyl-prolyl cis-trans isomerase FKBP1A, also showed differential expression, supporting the multifactorial nature of reproductive failure.
Conclusions: This study demonstrates that specific plasma proteins—particularly ERAP2 andβ-arrestin-1—may serve as biomarkers for reproductive failure. While limited by a small sample size and variation in treatment timing, these preliminary findings provide valuable insights into the proteomics of immune infertility and miscarriage. Future large-scale studies with functional validation are warranted to confirm these findings and explore their clinical applicability.