Quantitative assessment of CD4/CD8 ratio and its impact among pediatric and adolescent patients with hemophilia A

Abstract

Background Hemophilic arthropathy, the hallmark of severe hemophilia A, arises from persistent immune-driven inflammation due to chronic exposure to blood-derived metabolites. In hemophilia A, FVIII-specific memory B cells play a key role in sustaining immune response against exogenous FVIII, resulting in inhibitor formation, with the role of cell-mediated immunity, particularly the CD4/CD8 ratio, in shaping the immune dysregulation in hemophilia patients remains poorly understood. Aim Quantitative flow cytometric assessment of peripheral blood CD4/CD8 ratio in pediatric and adolescent patients with hemophilia A, and its role as a biomarker for early detection of joint affection. Patients and methods A 6-month cross-sectional study included 65 patients with hemophilia A following at the pediatric hematology clinic at Ain Shams University. Data retrieved from patients’ files included annual bleeding rate (ABR), FVIII level, and inhibitor status. Assessment of joints functional independence score in hemophilia (FISH), hemophilia joint health score (HJHS), and musculoskeletal ultrasound (US), in addition to the flow cytometric measurement of CD4/CD8 ratio. Results In our study, 57 (87.7%) patients had target joints and showed, before prophylaxis, higher ABR, US score, and HJHS but without significant difference. However, the FISH score was significantly lower ( P =0.016) in patients with target joints. Following prophylaxis, the ABR ( P =0.038), US ( P =0.038), and FISH ( P =0.016) scores showed significant differences, with worse scores observed in these patients. A significantly higher CD4/CD8 ratio was reported in patients diagnosed at birth. Among the target joints, the right knee showed the highest ratios, while the left hip and right ankle had the lowest, with a P value of 0.003. No significant correlations were found between the CD4/CD8 ratio and the ABR, HJHS, and FISH scores prior to prophylaxis, while strong negative correlations were observed with the current HJHS, as well as the US soft tissue and osteochondral scores.