The Conundrum of Lymphocyte and CD4+ Alteration in IGRA Results of Transfusion-dependent Thalassemia After Vitamin D Supplementation: An Open-label, Single-arm Clinical Study
Mohammad Ghozali (1)*, Findania Ulfah Afanin Kustandari (2)*, Nur Melani Sari (3), Suhendra Praptama (2), Agnes Rengga Indrati (3), Budi Setiabudiawan (4), Ramdan Panigoro (1)

(1) Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia.

(2) Faculty of Medicine, Universitas Padjadjaran, Sumedang, West Java, Indonesia.

(3) Department of Clinical Pathology, Faculty of Medicine, Maranatha Christian University, Bandung, Indonesia.

(4) Departement of Pediatrics, Universitas Padjadjaran, Bandung, West Java, Indonesia.

Abstract

Introduction: Iron overload and anemia in transfusion-dependent thalassemia patients can impair lymphocytes and CD4+ T cell function, increasing infection susceptibility. Immune cells possess vitamin D receptors (VDR) and exhibit immunomodulation- however, the effect of vitamin D supplementation requires additional investigation.
Purpose: Assess the impact of vitamin D supplementation on CD4+ T lymphocytes in transfusion-dependent thalassemia patients by comparing interferon-gamma release assay (IGRA) results.
Methods: A non-randomized, open-label trial was performed on pediatric beta-thalassemia major patients undergoing regular blood transfusions and latent tuberculosis screening using QFT-GIT at Hasan Sadikin General Hospital, Bandung, Indonesia. Participants received 800 IU/day or 2000 IU/day of cholecalciferol based on their vitamin D status. After 8 weeks, various parameters, including iron status, vitamin D levels, hematological profile, IGRA, CD4+ T cell count and proportion, and lymphocyte levels were assessed. Transfusion profiles, erythrocyte indices, iron status, and 25(OH)D levels between groups were compared using unpaired student t-tests, while efficacy endpoints were analyzed with paired student t-tests.
Results: Fifty-seven iron overload patients showed a significant increase in vitamin D levels after supplementation (9.45 ng/dL (6.93-15.77) to 10.95 ng/dL (8.31-19.81)- P=0.003). The QFT-GIT indicated 33 participants (26%) in the indeterminate group. All subjects exhibited a significantly low CD4+ T cell count post-supplementation, with higher CD4+ T cell count, lymphocyte count, and lymphocyte proportion observed in the determinate group.
Conclusion: Low-dose vitamin D supplementation modulated CD4+ T cell counts and increased lymphocyte numbers, particularly in immunocompetent transfusion-dependent thalassemia.

Keywords: Vitamin D, CD4+ T Cell, Thalassemia, Interferon-gamma

Topic: Genetic and Molecular Biology