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Performance of Soluble CD28 and CTLA4 as a Potential Marker of Immunosenescence Pratama, Mirza Zaka; Handono, Kusworini; Poetri, Levrita Nindya; Maghfirah, Halimi Bidaimi
Clinical and Research Journal in Internal Medicine Vol. 6 No. 1 (2025): Volume 6 No 1, May 2025
Publisher : Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.mrj.2025.006.01.05

Abstract

Background: Immunosenescence is a condition of decreased function of the immune system that is generally found in elderly individuals. Several costimulatory molecules, such as CD28 and CTLA-4 have been investigated for their essential role in the immune aging process. Aim: This study aimed to determine the role of the soluble costimulatory molecules in immunosenescence. Methods: This study was observational research with cross-sectional approach. Samples were tested using ELISA and flow cytometry examination. Statistical analysis was conducted using independent T-test or Kruskal-Wallis comparison test. Correlation between each biomarker was determined with Pearson or Spearman correlation test. Diagnostic performances of each biomarked were assessed using ROC curve. Results: This study involved 52 subjects, of which 20 were young individuals aged between 20 to 28 years and 32 were elderly individuals aged between 60 to 85 years. In this study we found that CD4CD28+ and CD8CD28+ T cells were lower in elderly group (p<0.001), while CD4CD57+ and CD8CD57+ T cells were higher in elderly group (p<0.001). sCD28 and sCTLA-4 were significantly higher (p 0.039 and p 0.025 respectively) in old individuals than in young individuals. CD8CD28+ and sCD28 exhibit a significant negative moderate correlation (p=0.007, r= -0.368) meanwhile sctla4 has no correlation with surface immunosenescence markers. Based on the results of roc analysis, sCTLA-4 was the best predictor to determine immunosenescence with area under curve of 0.7. The cut-off value for sCTLA-4 to determine immunosenescence is 26.5 ng/ml with sensitivity and specificity 58.6% and 63.2% respectively. Conclusion: sCTLA-4 as a soluble costimulatory molecule can be developed as promising predictive biomarkers of immunosenescence, which could be detected more quickly and efficiently using elisa as an alternative to flowcytometry.
The Role of Soluble Costimulatory Molecules as the Biomarkers for Aging Predictors Handono, Kusworini; Pratama, Mirza Zaka; Susianti, Hani; Wahono, Cesarius Singgih; Firdaningrum, Nimas Eka; Famuji, Siti Roziah Ria; Sumarta, Norma Hanifah; Rizky Fachry, Ade Wildan; Poetri, Levrita Nindya; Kalim, Handono
Jurnal Kedokteran Brawijaya Vol. 32 No. 3 (2023)
Publisher : Fakultas Kedokteran Universitas Brawijaya

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.21776/ub.jkb.2022.032.03.4

Abstract

This study aimed to determine the role of the soluble costimulatory molecules in aging and the association with the presence of comorbid in aged individuals. Thirty-two elderly and twenty healthy subjects were included in this study. The soluble costimulatory molecules sCD28, sCD80, sCD86, sCD163, and sCTLA4 were measured using ELISA. The presence of comorbid was documented from medical records. Charlson Comorbidity Index (CCI) was measured to evaluate the survival/mortality risk for the subjects. The levels of the majority of soluble costimulatory molecules significantly increased in the elderly participants, while the level of sCD86 was comparable. There were weak positive correlations between the subject's age and levels of sCD28 (R=0.214, p=0.048), sCTLA4 (R=0.238, p=0.041), and sCD80 (R=0.317, p=0.012). sCD80 were discovered to be the best to predict immune aging in the elderly with AUC 0.71 [0.57-0.86], sensitivity 53,1%, specificity 80.0%, and cut off 129ng/ml. Most of the elderly participants had at least one comorbid, in which approximately 25.0% and 3.1% of the subjects were classified as mild and moderate CCI. Multivariate analysis showed that comorbidities in elderly individuals have been associated with levels of sCTLA4 ≥26.5ng/ml and sCD80 ≥129.0ng/ml. Furthermore, subjects with comorbid (CCI ≥1) were associated with sCD80 ≥129.0ng/ml (OR 12.44 [95% CI 1.32–117.03], p=0.027). Considering these results, sCD28, sCTLA4, and sCD80 can be developed as biomarkers for predicting immune aging and elderly comorbidities, respectively.