Immunological imbalance in microcephalic children with congenital Zika virus syndrome
Amanda Costa Ayres Salmeron1, Wallace Pitanga Bezerra2, Rafaela Lúcia Lopes de Souza3
1Edmond and Lily Safra International Institute of Neuroscience, Santos Dumont Institute, Macaiba, Rio Grande do Norte, Brazil.
Insights
Congenital Zika virus syndrome (CZS) in microcephalic children impacts the immune system, causing enlarged lymphoid organs and altered immune cell function. This broadens the known symptoms of CZS and may inform new treatments and vaccination strategies.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Congenital Zika virus syndrome (CZS) is known for neurological effects in microcephalic children.
- Other systemic alterations beyond neurological symptoms in CZS require further investigation.
Purpose of the Study:
- To investigate the immune system alterations in microcephalic children with CZS.
- To characterize the impact of CZS on lymphoid organs and immune cell morphology and function.
Main Methods:
- Ultrasound analysis of thymus, spleen, and lymph nodes compared to healthy controls.
- Blood cell counts and morphological analysis (neutrophils, lymphocytes).
- Measurement of cytokine levels (IFN-γ, IL-2, IL-4, IL-5, type I IFNs) and assessment of cellular immune memory via tuberculin skin test (PPD).
Main Results:
- Enlarged thymus, spleen, and cervical lymph nodes observed in CZS children.
- Increased eosinophils and altered neutrophil/lymphocyte morphology noted, independent of other infections.
- Elevated levels of key cytokines (IFN-γ, IL-2, IL-4, IL-5, type I IFNs) and deficient cellular immune memory (low PPD reactivity) were found.
Conclusions:
- CZS significantly affects primary and secondary lymphoid organs in microcephalic children.
- CZS alters immune cell morphology and function, expanding the spectrum of known symptoms.
- Findings may guide the development of targeted therapies and improved vaccination protocols for CZS patients.
Abstract:
Microcephalic children due congenital Zika virus syndrome (CZS) present neurological symptoms already well described. However, several other alterations can also be observed. Here, we aimed to evaluate the immune system of microcephaly CZS children. We showed that these patients have enlarged thymus, spleen and cervical lymph nodes, analysed by ultrasound and compared to the reference values for healthy children. In the periphery, they have an increase in eosinophil count and morphological alterations as hypersegmented neutrophils and atypical lymphocytes, even in the absence of urinary tract infections, parasitological infections or other current symptomatic infections. Microcephalic children due CZS also have high levels of IFN-γ, IL-2, IL-4, IL-5 and type I IFNs, compared to healthy controls. In addition, this population showed a deficient cellular immune memory as demonstrated by the low reactivity to the tuberculin skin test even though they had been vaccinated with BCG less than 2 years before the challenge with the PPD. Together, our data demonstrate for the first time that CZS can cause alterations in primary and secondary lymphoid organs and also alters the morphology and functionality of the immune system cells, which broadens the spectrum of CZS symptoms. This knowledge may assist the development of specific therapeutic and more efficient vaccination schemes for this population of patients.
