Immunological Features in Hyper-IgE Syndrome: A Comparison of Infectious and Non-Infectious States—A Retrospective Study

Abstract Background This study aimed to clarify the impact of infections on the immune status of patients with hyper-IgE syndrome (HIES) and to explore cell-intrinsic immune homeostasis alterations associated with underlying genetic mutations. Methods A retrospective analysis was performed on five patients with STAT3 -mutated HIES (STAT3-HIES) and one patient with a novel compound heterozygous DOCK8 -mutated HIES (DOCK8-HIES). Comparisons were performed using the Mann–Whitney U test and Wilcoxon signed-rank test, as appropriate. Results In the cohort, STAT3 mutations had minimal impact on lymphocyte subsets (CD3⁺ T, CD4⁺ T, CD8⁺ T, CD19⁺ B, and CD16⁺CD56⁺ natural killer (NK) cells), immunoglobulins (IgG, IgM, and IgA), and complement levels (C3 and C4). Importantly, patients with HIES exhibited a decline in lymphocyte subsets during infectious episodes, particularly in the single DOCK8-HIES patient, indicating that patients with HIES display dynamic immune profiles shaped by the infection status. Furthermore, elevated serum IgE levels were not universally observed and showed no clear correlation with infectious activity. Hematopoietic stem cell transplantation resulted in the normalization of markedly elevated IgE levels and favorable outcomes in the two patients with STAT3-HIES. Conclusions These findings highlight infection-associated variability in the immune profiles of patients with HIES and may inform therapeutic decision-making in complex cases.