C3a and TNF-α as potential biomarkers in recurrent spontaneous abortion: insights from integrated protein and gene...

Various factors, cause recurrent spontaneous abortion (RSA); however, nearly half of the cases remain unexplained. Most abortions occur during the first trimester, highlighting the importance of early molecular and immunological investigations. Growing evidence links unexplained RSA to maternal immune dysregulation. Complement component C3a and Tumor Necrosis Factor-alpha (TNF-α) are key inflammatory mediators that may serve as biomarkers for RSA.

Seventy-five women in their first trimester of pregnancy were enrolled (33 with normal pregnancies and 42 with RSA). Serum protein concentrations were quantified via Enzyme Linked Immunosorbent Assay (ELISA), and mRNA transcripts in whole blood were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Serum C3a (p = 0.004) and TNF-α (p = 0.016) were significantly elevated in RSA group. TNF-α mRNA expression was also significantly increased, reflected by lower delta quantification cycle values (p = 0.0003; post hoc power = 98%), while C3 mRNA showed no significant difference. Receiver Operating Characteristic (ROC) curve analyses indicated moderate diagnostic accuracy for serum C3a, TNF-α, and higher accuracy for TNF-α expression with Area Under the Curve (AUC) of 0.776. Correlation analysis indicated a significant association between maternal age and TNF-α transcription. A strong correlation was observed between C3a and TNF-α proteins (p < 0.0001).

C3a and TNF-α, particularly TNF-α mRNA, may serve as potential biomarkers for RSA. These findings support immune dysregulation as a pathogenic factor and suggest that combined protein and gene expression analyses may improve early risk identification.