Lymphocyte subsets in untreated thalassemia patients: differences by genotype and age

The Lymphocyte subsets in treatment-naïve patients and their variations among different genetic subtypes and age groups remain poorly characterized.

To characterize the distribution of lymphocyte subsets in treatment-naïve thalassemia patients, stratified by both genetic subtype and age group (pediatric vs. adult), compared to healthy controls. This investigation included 535 participants, comprising 307 healthy controls (104 pediatric and 203 adult patients) and 228 untreated thalassemia patients (123 α-thalassemia, 83 β-thalassemia, and 22 compound α+β-thalassemia cases). Genotyping was performed using NGS, while flow cytometry was utilized to quantify peripheral blood lymphocyte subsets.

Pediatric patients: All thalassemia subtypes (α, β, α+β) showed significantly higher Tregs frequencies than healthy pediatric controls (all P < 0.0001). Pediatric α+β-thalassemia patients had lower CD3+ T-cell proportions than β-thalassemia patients.Adult patients: Adult β+-thalassemia patients had significantly higher B-cell and Tregs frequencies than healthy adult controls (P = 0.037, P = 0.034). Adult α+β-thalassemia patients had lower CD4+ T-cell percentages than healthy adult controls (P = 0.040).Age-group comparisons: Tregs levels were significantly higher in healthy adults than in healthy pediatric individuals (P < 0.0001). Pediatric β+-thalassemia patients had lower CD3+ T-cell frequencies than adult β+-thalassemia patients (P = 0.009). Pediatric patients with Hb Constant Spring heterozygosity or Codons 41/42 (-TTCT) β0 heterozygosity also had lower CD3+ and CD4+ T-cell proportions than corresponding adult patients (all P < 0.05).

This study clarified the distribution of lymphocyte subsets in treatment-naïve patients with thalassemia. It was found that the number of Tregs in healthy pediatric was significantly lower than that in healthy adults. Moreover, the level of Tregs was markedly higher in pediatric with thalassemia than in healthy pediatric. These findings may help deepen the understanding of immune dysregulation in thalassemia patients and facilitate the formulation of clinical management strategies.