Detection of HLA-DR on microglia in the human brain is a function of both clinical and technical factors

L A Mattiace1, P Davies, D W Dickson

  • 1Department of Pathology (Neuropathology), Albert Einstein College of Medicine of Yeshiva University, Bronx 10461.

Insights

Human leukocyte antigen - DR (HLA-DR) is detected on microglia, the brain

Area of Science:

  • Neuroimmunology
  • Cellular Biology
  • Pathology

Background:

  • Detection of Human Leukocyte Antigen - DR (HLA-DR), a class II major histocompatibility antigen, on glial cells is influenced by tissue processing and clinical factors.
  • Glial cells expressing HLA-DR exhibit characteristics of microglia, confirmed by co-labeling with microglial markers like LN-1, Leu-M5, and leukocyte common antigen (LCA).

Purpose of the Study:

  • To investigate the expression patterns of HLA-DR on microglia in different brain regions and in relation to various clinical conditions.
  • To determine if HLA-DR expression on microglia is constitutive or induced under specific pathological circumstances.

Main Methods:

  • Immunohistochemical staining for HLA-DR on glial cells in post-mortem brain tissue.
  • Microscopic and ultrastructural analysis to identify and characterize HLA-DR-positive glial cells.
  • Co-labeling studies with established microglial markers (LN-1, Leu-M5, LCA).
  • Comparison of HLA-DR expression in subjects with sudden death versus those with chronic debilitating illnesses (Alzheimer's disease, carcinomatosis).

Main Results:

  • HLA-DR-positive microglia were consistently found in white matter across all subjects, irrespective of clinical status.
  • In sudden death cases, HLA-DR-positive microglia were scarce in gray matter compared to white matter.
  • Subjects with chronic illnesses, including Alzheimer's disease and carcinomatosis, showed significantly increased HLA-DR-positive microglia in both gray and white matter.
  • In Alzheimer's disease, microglia aggregated around compact senile plaques and were loosely associated with diffuse amyloid deposits.

Conclusions:

  • HLA-DR expression appears to be constitutive in white matter microglia.
  • HLA-DR expression is induced in gray matter microglia during chronic disease states, particularly in association with amyloid deposits.
  • These findings suggest a role for microglia and HLA-DR in the pathogenesis of chronic neurological diseases like Alzheimer's.

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