Association between histological alterations in the thymus and sudden infant death syndrome

J Forensic Leg Med. 2018 Apr:55:8-13. doi: 10.1016/j.jflm.2018.02.007. Epub 2018 Feb 8.

Abstract

Introduction: Sudden infant death syndrome (SIDS) involves the death of an infant during the first year of life and it is among the leading causes of infant mortality worldwide. One hypothesis regarding the pathogenesis of SIDS is that it results from a combination of three independent factors: endogenous vulnerability, a critical time window during postnatal development, and exogenous stressors. This hypothesis is known as the "triple-risk model".

Methods: In this study, we used an immunohistological approach to compare the cellular microenvironments of thymuses from 19 infants whose sudden death was classified as SIDS and a control group, which consisted of thymuses from age-matched children undergoing surgery for various congenital heart defects. We hypothesized that morphological signs of stress-related thymic involution would be present.

Results: Based on our observations, we found evidence that the proliferation and maturation of T-lymphocytes in the thymuses of infants with SIDS were suppressed. We observed enhanced macrophage activity, suggesting an increase in the apoptosis of lymphocytes and decrease in number of thymic dendritic cells and myoid cells. Significant apoptosis of thymic lymphocytes without cell regeneration typically leads to atrophy of the thymus. All cellular events we observed resemble the initial stage of stress-related thymic involution.

Conclusion: These results support the "triple-risk model," suggesting that certain exogenous stressors might be involved in the pathogenesis of SIDS. This was probably not recognized during the autopsies of infants who died suddenly.

Keywords: Immunohistochemistry; SIDS; Stress-related involution; Thymus.

MeSH terms

  • Actins / analysis
  • Antigens, CD / analysis
  • Antigens, Differentiation, Myelomonocytic / analysis
  • Apoptosis
  • Atrophy
  • Case-Control Studies
  • Cell Count
  • Cell Proliferation
  • Dendritic Cells / pathology
  • Desmin / analysis
  • Female
  • Forensic Pathology
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Ki-67 Antigen / analysis
  • Lymphocytes / pathology
  • Macrophages / pathology
  • Male
  • Muscle, Smooth / pathology
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • S100 Proteins / analysis
  • Sudden Infant Death / pathology*
  • T-Lymphocytes / pathology
  • Thymus Gland / pathology*

Substances

  • Actins
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • BCL2 protein, human
  • CD68 antigen, human
  • Desmin
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • S100 Proteins