Exploratory analysis of immune profiles in 2- to 3-year-old children with growth stunting.

BACKGROUND: Growth stunting, which is associated with metabolic and immunological changes, remains a concerning global challenge. However, the etiology and underlying pathophysiological mechanisms remain elusive. OBJECTIVES: This study was aimed at exploring humoral, cytokine, and T-cell immune profiles in children 2-3 years of age, with or without stunting. METHODS: A cross-sectional exploratory study was conducted among children with or without stunting. Antibody isotypes (IgM, IgG1, IgG2, IgG3, IgG4, IgA, and IgE) were measured with a ProcartaPlex Human Antibody Isotyping Panel 7-Plex kit. Proportions of T lymphocytes and Tregs were determined through flow cytometry. Cytokine levels (IL-6, TNF-α, and IL-10) were measured with a human cytokine kit, read with an x-MAP (Luminex200) instrument. Group differences were analyzed with t-tests or Mann-Whitney tests. False discovery rate (FDR) correction was applied. Multivariable logistic regression provided adjusted odds ratios (AORs). ROC-derived cut-off points were used for exploratory quadrant analysis of significant biomarkers. RESULTS: Unadjusted analyses indicated higher IgM, IgG2, IgG3, IL-6, and IL-6/IL-10 ratios in children with rather than without stunting (p ≤ 0.05). After FDR correction, no biomarkers achieved conventional significance. However, several markers, including IL-6 and IgG3, approached the exploratory threshold (FDR < 0.20) commonly accepted in hypothesis-generating immunological analyses. In multivariable models, IL-6 remained associated with stunting (AOR 1.731; 95% CI 1.044-2.870), and IgG3 showed the largest effect estimate (AOR 4.055; 95% CI 0.813-20.226), despite non-significance. Quadrant analysis demonstrated substantially elevated odds of stunting in children with concurrent high IL-6 and high IgG3 (OR 9.56-18.7). CONCLUSION: Exploratory analyses indicate biologically plausible inflammatory-humoral activation signatures in children with stunting, warranting confirmation in larger longitudinal studies.