{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:29:23Z","timestamp":1760146163251,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T00:00:00Z","timestamp":1728345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/diagnostics14192240","type":"journal-article","created":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T04:29:26Z","timestamp":1728361766000},"page":"2240","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Morphological Study of HLA-DR-Immunopositive Cells in Multiple Sclerosis Lesions and Their Implications for Pathogenesis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4922-4112","authenticated-orcid":false,"given":"Murad","family":"Alturkustani","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee-Cyn","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 5C1, Canada"},{"name":"Pathology and Laboratory Medicine, London Health Sciences Centre (LHSC), London, ON N6A 5W9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/0165-5728(94)90075-2","article-title":"Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions","volume":"51","author":"Bo","year":"1994","journal-title":"J. Neuroimmunol."},{"key":"ref_2","unstructured":"Love, S., Budka, H., Ironside, J.W., and Perry, A. (2015). Demyelinating diseases. Greenfield\u2019s Neuropathology, CRC Press, Taylor & Francis Group. [9th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1093\/jnen\/nlad046","article-title":"Microglia subtypes in acute, subacute, and chronic multiple sclerosis","volume":"82","author":"Prineas","year":"2023","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_4","first-page":"27","article-title":"Loss of Ramified Microglia Precedes Axonal Spheroid Formation in Adult-Onset Leukoencephalopathy with Axonal Spheroids","volume":"1","author":"Alturkustani","year":"2020","journal-title":"Free Neuropathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/cei\/uxae023","article-title":"Quantifying microglial morphology: An insight into function","volume":"216","author":"Green","year":"2024","journal-title":"Clin. Exp. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: A field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1126\/science.1110647","article-title":"Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo","volume":"308","author":"Nimmerjahn","year":"2005","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1016\/j.neuron.2022.06.023","article-title":"Microglia in multiple sclerosis: Protectors turn destroyers","volume":"110","author":"Yong","year":"2022","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00401-016-1653-y","article-title":"An updated histological classification system for multiple sclerosis lesions","volume":"133","author":"Kuhlmann","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1002\/ana.24497","article-title":"Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque","volume":"78","author":"Frischer","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.stem.2010.08.014","article-title":"Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis","volume":"7","author":"Sierra","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Pukoli, D., and Vecsei, L. (2023). Smouldering Lesion in MS: Microglia, Lymphocytes and Pathobiochemical Mechanisms. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612631"},{"key":"ref_13","first-page":"5859","article-title":"White matter cellular changes in ischemic injuries","volume":"14","author":"Alturkustani","year":"2022","journal-title":"Am. J. Transl. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00401-013-1082-0","article-title":"Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons","volume":"125","author":"Singh","year":"2013","journal-title":"Acta Neuropathol."},{"key":"ref_15","first-page":"156","article-title":"Clusters of activated microglia in normal-appearing white matter show signs of innate immune activation","volume":"9","author":"Singh","year":"2012","journal-title":"J. Neuroinflamm."},{"key":"ref_16","first-page":"187","article-title":"Different pathological processes for acute white matter lesions in multiple sclerosis","volume":"42","author":"Alturkustani","year":"2020","journal-title":"Malays. J. Pathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1002\/glia.24148","article-title":"The roles of microglia and astrocytes in phagocytosis and myelination: Insights from the cuprizone model of multiple sclerosis","volume":"70","author":"Sen","year":"2022","journal-title":"Glia"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Mado, H., Adamczyk-Sowa, M., and Sowa, P. (2023). Role of Microglial Cells in the Pathophysiology of MS: Synergistic or Antagonistic?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24031861"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, X., Chen, F., Sun, M., Wu, N., Liu, B., Yi, X., Ge, R., and Fan, X. (2023). Microglia in the context of multiple sclerosis. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1157287"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/19\/2240\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:09:00Z","timestamp":1760112540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/14\/19\/2240"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,8]]},"references-count":19,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["diagnostics14192240"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics14192240","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2024,10,8]]}}}