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Exploratory analysis of immune profiles in 2- to 3-year-old children with growth stunting
Rizana Fajrunni'mah1,2, Mohamad Sadikin3, Heri Wibowo4
1Doctoral Programme in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Insights
Growth stunting in children is linked to immune system changes. This study found potential inflammatory and antibody markers, like IL-6 and IgG3, associated with stunting, suggesting further research is needed.
Area of Science:
- Pediatric Immunology
- Global Health
- Nutritional Sciences
Background:
- Childhood growth stunting is a significant global health issue with unclear causes and mechanisms.
- Stunting is associated with altered metabolic and immune system functions.
- Understanding the immunological underpinnings of stunting is crucial for developing effective interventions.
Purpose of the Study:
- To investigate humoral, cytokine, and T-cell immune profiles in stunted versus non-stunted children aged 2-3 years.
- To identify potential immune biomarkers associated with growth stunting.
- To explore the relationship between specific immune markers and stunting prevalence.
Main Methods:
- Cross-sectional exploratory study design involving children with and without stunting.
- Measurement of antibody isotypes (IgM, IgG subclasses, IgA, IgE) using a multiplex assay.
- Flow cytometry analysis of T lymphocyte subsets and regulatory T cells (Tregs).
- Quantification of key cytokines (IL-6, TNF-α, IL-10) using multiplex immunoassay.
- Statistical analysis including t-tests, Mann-Whitney tests, FDR correction, and multivariable logistic regression.
Main Results:
- Unadjusted analyses revealed higher levels of IgM, IgG2, IgG3, and IL-6 in stunted children.
- After FDR correction, no biomarkers reached conventional statistical significance, but IL-6 and IgG3 approached exploratory thresholds.
- Multivariable analysis indicated an association between IL-6 and stunting (AOR 1.731), with IgG3 showing a large effect estimate (AOR 4.055).
- Concurrent high levels of IL-6 and IgG3 were associated with significantly elevated odds of stunting (OR 9.56-18.7).
Conclusions:
- Exploratory findings suggest potential inflammatory and humoral immune activation signatures in children with stunting.
- Specific markers like IL-6 and IgG3 may play a role in the pathophysiology of stunting.
- Larger, longitudinal studies are warranted to confirm these immune profiles and their causal relationship with 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.
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