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A Morphological Study of HLA-DR-Immunopositive Cells in Multiple Sclerosis Lesions and Their Implications for
Murad Alturkustani1,2, Lee-Cyn Ang2,3
1Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Background:
Multiple sclerosis (MS) is characterized by white matter demyelinating plaques, which can be classified as active, chronic active, or chronic inactive based on the extent of demyelination, cellularity, and inflammation. Microglia and macrophages play a central role in these processes. This study aimed to investigate the morphological characteristics of HLA-DR-immunopositive cells in these plaques to improve our understanding of the roles of these cells in MS plaques.
Methods:
This study is a retrospective post-mortem histopathological study. We analyzed 90 plaques from 6 MS cases. Of the plaques studied, 77 were grouped into three categories: 28 active, 34 chronic active, and 15 chronic inactive. Additionally, five vacuolated white matter lesions, two axonal degeneration lesions, and six lesions with mixed histological features were included. Six control cases were also examined to assess HLA-DR-immunopositive cell expression across various age groups. The cells were classified based on their morphology into two types: round cells without processes (macrophages) and cells with varying processes and shapes (ramified microglia).
Results:
Both macrophages and ramified microglia were present in all lesion types, with a focus on identifying the predominant cell type. Of the 28 active plaques, macrophages were the primary cell type in 25 plaques, while ramified microglia predominated in 3. In the center of 49 chronic plaques, scattered ramified microglia were observed in 46, with three plaques showing a predominance of macrophages. Among the 34 chronic active lesions, ramified microglia were the main cell type in the periphery of 32 plaques, with the remaining two predominantly exhibiting macrophages.
Conclusions:
The predominance of macrophages in active lesions and the presence of scattered ramified microglia in the center of chronic plaques are consistent with the phagocytic role of macrophages. Meanwhile, the prevalence of ramified microglia at the periphery of chronic active lesions suggests a potential protective function in maintaining lesion stability.
Insights
In multiple sclerosis (MS) lesions, macrophages dominate active plaques, while ramified microglia are prevalent in chronic active lesions, suggesting distinct roles in disease progression and stability.
Area of Science:
- Neuroimmunology
- Neuropathology
Background:
- Multiple sclerosis (MS) is characterized by demyelinating white matter plaques.
- These plaques are classified as active, chronic active, or chronic inactive based on demyelination, cellularity, and inflammation.
- Microglia and macrophages are key players in MS plaque pathogenesis.
Purpose of the Study:
- To investigate the morphological characteristics of HLA-DR-immunopositive cells in MS plaques.
- To elucidate the distinct roles of macrophages and microglia in different MS lesion types.
Main Methods:
- Retrospective post-mortem histopathological analysis of 90 MS plaques from 6 cases.
- Classification of lesions into active, chronic active, chronic inactive, and other categories.
- Morphological classification of HLA-DR-immunopositive cells into macrophages (round) and ramified microglia (process-bearing).
Main Results:
- Macrophages predominated in 25 of 28 active MS plaques.
- Ramified microglia were the main cell type in the periphery of 32 of 34 chronic active lesions.
- Scattered ramified microglia were observed in the center of 46 of 49 chronic plaques.
Conclusions:
- Macrophage predominance in active lesions supports their phagocytic role in clearing debris.
- Ramified microglia in chronic active lesions suggest a potential role in lesion stability.
- Distinct cellular morphologies and distributions indicate specialized functions for macrophages and microglia in MS pathogenesis.
