Frontiers in immunology · 2026
Anti-GPIIIa antibody and CD4 count identify an autoimmune-enriched phenotype of HIV-associated thrombocytopenia: development and internal validation of a clinical nomogram.
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Liu Xia, Wen Lemin, Zhong Zhoulin, Qiang Hangbiao, Mo Lida, Dong Wenyi, Huang Wen, Nong Shuyu, Huang Zheng, Xie Zhiman, Yu Mei
Аннотация
BACKGROUND: Thrombocytopenia is a frequent complication of human immunodeficiency virus (HIV) infection, tire arising through diverse mechanisms including autoimmune platelet destruction, advanced immunodeficiency, and systemic comorbidities. Distinguishing thrombocytopenia driven primarily by autoimmune platelet destruction from that related to advanced immunodeficiency remains a clinical challenge, as current standard markers often fail to stratify these distinct pathophysiological phenotypes.
METHODS: We conducted a case-control study enrolling 196 HIV-infected individuals (98 thrombocytopenia cases, 98 controls) to develop a clinical prediction model for HIV-associated thrombocytopenia. Candidate predictors were identified through univariable analysis, and AIC-based backward stepwise logistic regression was used to construct a parsimonious multivariable model. A nomogram was generated for bedside risk stratification, and dose-response analysis examined CD4+ T-cell counts and anti-platelet autoimmunity. Model performance was assessed through bootstrap resampling and 10-fold cross-validation, calibration by the Hosmer-Lemeshow test, and clinical utility by Decision Curve Analysis (DCA).
RESULTS: Anti-GPIIIa antibody positivity emerged as the dominant predictor of thrombocytopenia (aOR = 35.3; 95% CI: 9.2-135.6; P < 0.001). The final 4-variable model-incorporating anti-GPIIIa antibody, CD4+ count, albumin, and neutrophil count-achieved AUC of 0.862 (95% CI: 0.811-0.913). At the optimal cutoff, the model demonstrated high specificity (96.9%) and positive predictive value (95.6%). Internal validation confirmed robustness, with bootstrap-corrected AUC of 0.857 (optimism = 0.005) and mean cross-validation AUC of 0.867 ± 0.055. Dose-response analysis (CD4 ≤600 cells/μL; n = 167) revealed distinct risk trajectories: anti-GPIIIa-positive patients maintained consistently high thrombocytopenia risk (100% at CD4 <150 cells/μL, declining to approximately 80% at CD4 >300 cells/μL), whereas antibody-negative patients showed progressive risk reduction (from ~58% at CD4 <50 to ~17% at CD4 >380 cells/μL); the CD4 × anti-GPIIIa interaction was not statistically significant (P = 0.427).
CONCLUSIONS: This parsimonious model identifies an autoimmune-enriched phenotype of HIV-associated thrombocytopenia, characterized by anti-GPIIIa positivity and reduced immune and hematological reserves. Rather than confirming an immune-mediated etiology, the nomogram supports risk stratification to identify patients warranting further immunological evaluation. As treatment response was not prospectively evaluated and no independent reference standard was applied, external validation and prospective studies are required before clinical implementation.
METHODS: We conducted a case-control study enrolling 196 HIV-infected individuals (98 thrombocytopenia cases, 98 controls) to develop a clinical prediction model for HIV-associated thrombocytopenia. Candidate predictors were identified through univariable analysis, and AIC-based backward stepwise logistic regression was used to construct a parsimonious multivariable model. A nomogram was generated for bedside risk stratification, and dose-response analysis examined CD4+ T-cell counts and anti-platelet autoimmunity. Model performance was assessed through bootstrap resampling and 10-fold cross-validation, calibration by the Hosmer-Lemeshow test, and clinical utility by Decision Curve Analysis (DCA).
RESULTS: Anti-GPIIIa antibody positivity emerged as the dominant predictor of thrombocytopenia (aOR = 35.3; 95% CI: 9.2-135.6; P < 0.001). The final 4-variable model-incorporating anti-GPIIIa antibody, CD4+ count, albumin, and neutrophil count-achieved AUC of 0.862 (95% CI: 0.811-0.913). At the optimal cutoff, the model demonstrated high specificity (96.9%) and positive predictive value (95.6%). Internal validation confirmed robustness, with bootstrap-corrected AUC of 0.857 (optimism = 0.005) and mean cross-validation AUC of 0.867 ± 0.055. Dose-response analysis (CD4 ≤600 cells/μL; n = 167) revealed distinct risk trajectories: anti-GPIIIa-positive patients maintained consistently high thrombocytopenia risk (100% at CD4 <150 cells/μL, declining to approximately 80% at CD4 >300 cells/μL), whereas antibody-negative patients showed progressive risk reduction (from ~58% at CD4 <50 to ~17% at CD4 >380 cells/μL); the CD4 × anti-GPIIIa interaction was not statistically significant (P = 0.427).
CONCLUSIONS: This parsimonious model identifies an autoimmune-enriched phenotype of HIV-associated thrombocytopenia, characterized by anti-GPIIIa positivity and reduced immune and hematological reserves. Rather than confirming an immune-mediated etiology, the nomogram supports risk stratification to identify patients warranting further immunological evaluation. As treatment response was not prospectively evaluated and no independent reference standard was applied, external validation and prospective studies are required before clinical implementation.