{"id":42617,"date":"2022-01-23T10:57:14","date_gmt":"2022-01-23T16:57:14","guid":{"rendered":"https:\/\/www.erdheim-chester.org\/?p=42617"},"modified":"2026-10-08T16:18:48","modified_gmt":"2026-10-08T21:18:48","slug":"fordermittel-2022-raumverstandnis","status":"publish","type":"post","link":"https:\/\/www.erdheim-chester.org\/de\/grants-2022-spatial-understanding\/","title":{"rendered":"R\u00e4umliches Verst\u00e4ndnis der Entstehung der Erdheim-Chester-Krankheit und der Mikroumgebung der L\u00e4sionen"},"content":{"rendered":"[et_pb_section global_module=\"47640\"][\/et_pb_section]\n

Year Awarded:<\/strong> 2012
\nAmount:<\/strong>\u00a0 50,000 USD<\/h4>\n

Dr. Egle Kvedaraite is a Postdoctoral Fellow with the Department of Pathology and Cancer Diagnostics at the Karolinska University Hospital \u2013 Unit of Molecular Neurobiology in Stockholm, Sweden. Dr. Kvedaraite was awarded the Early Career Investigator Award for $50,000 to conduct the study\u00a0Spatial understanding of Erdheim-Chester Disease origin and lesional microenvironment<\/a>.<\/p>\n

Final Report (December 2025)<\/h3>\n

The overarching\u202fobjective\u202fof this project was to gain a deeper understanding of the cellular and molecular heterogeneity of\u202fErdheim-Chester disease (ECD) and its relationship to the lesional microenvironment across affected tissues. A particular focus was placed on central nervous system (CNS) involvement and the mechanisms contributing to histiocytosis-associated neurodegeneration, a major clinical complication for which knowledge and therapeutic options\u202fremain\u202flimited. Through integrative spatial transcriptomics, single-cell genomics, and targeted proteomics, we have generated new insights into the immunopathology of ECD,\u202fincluding processes occurring within the brain,\u202fand\u202fidentified\u202fpromising biomarker candidates that may enable earlier detection of neurodegenerative disease in clinical practice.<\/p>\n

Achieved\u202fand achievements<\/h4>\n

Patient Material, Sample Selection, and Cohort Establishment:\u202fIn collaboration with Prof. Haroche, Prof. Emile, Dr. Charlotte, and neuropathologist Dr.\u202fPlu, we assembled a unique cohort of CNS and peripheral tissue samples from patients with ECD and related histiocytic disorders. In total:\u202f48 frozen CNS samples were selected from five ECD patients and two controls, representing a broad anatomical distribution including hippocampus, amygdala, cerebellum, pons, caudate nucleus, thalamus, and multiple cortical lesions;\u202fSix additional frozen samples were obtained from three ECD patients, two Langerhans cell histiocytosis (LCH) patients, and one Rosai-Dorfman-Destombes\u202fdisease (RDD) patient, providing valuable reference material.<\/p>\n

Peripheral biopsies\u202fincluded\u202fbone, skin, lymph node, and peri-renal tissue-covering the most common accessible sites of ECD disease activity.\u202fImportantly, two patients had matched CNS and peripheral biopsies, enabling direct comparison across tissue microenvironments.<\/p>\n

All samples were reviewed for clinical, radiological, and histopathological characteristics, including macrophage marker expression, immune infiltrates, and mutational status. Joint microscopy sessions were conducted at\u202fH\u00f4pital\u202fPiti\u00e9\u2013Salp\u00eatri\u00e8re and\u202fH\u00f4pital\u202fAmbroise-Par\u00e9 (travel supported by external funding, not the ECD Global Alliance). Final selected specimens were shipped to Stockholm for advanced molecular profiling.<\/p>\n

Specific accomplishments<\/h4>\n

Our work has uncovered previously unrecognized immunopathological pathways involved in histiocytosis-associated neurodegeneration, highlighting pronounced macrophage activation, dysregulation of decoy receptor systems, and contributions from both the innate and adaptive immune compartments. Together, these findings outline a mechanistic roadmap for future investigations aimed at clarifying the immunobiology of histiocytic disorders. In parallel, we\u202fidentified\u202fseveral promising biomarker candidates that are consistently elevated in patients with neurodegenerative manifestations of histiocytosis. Notably, we\u202fobserved\u202fincreased concentrations of neurofilament light chain (NFL) in patients with ECD and other\u202fhistiocytoses\u202fwho developed neurodegenerative disease, including individuals receiving BRAF\/MEK inhibitor therapy. These results\u202findicate\u202fthat ongoing neuroaxonal injury may persist despite targeted MAPK-pathway inhibition. A comprehensive report of these findings will be presented in our manuscript,\u202f\u201cTargeted Proteomics Reveals Histiocytosis-Associated Neurodegeneration Signatures\u201d\u202f(Kvedaraite et al., in preparation).<\/p>\n

Significance and future perspective<\/h4>\n

Collectively, our findings open new translational avenues for scientists working in the field of histiocytosis,\u202fdemonstrating\u202fthat current treatments, although\u202flife-saving, may be insufficient to prevent or reverse CNS complications such as neurodegenerative disease. The identification of robust biomarker candidates\u202fprovides an opportunity for clinicians\u202fto detect neurological involvement earlier and to\u202fmonitor\u202fdisease progression with greater precision. Moreover, the immunopathological insights generated by this work highlight specific macrophage signaling pathways and immune circuits that could be targeted by next-generation therapeutic strategies. These discoveries may\u202fultimately support\u202fthe development of novel immunomodulatory or pathway-specific interventions designed to mitigate neuroinflammation and neurodegeneration in ECD and related histiocytic disorders.<\/p>\n","protected":false},"excerpt":{"rendered":"

Dr. Egle Kvedaraite vom Karolinska-Universit\u00e4tsklinikum erh\u00e4lt einen mit 45.000 TP dotierten \u201eEarly Career Investigator Award\u201c, um die zellul\u00e4ren Urspr\u00fcnge und das Mikromilieu der Erdheim-Chester-Krankheit zu untersuchen. Die Forschung nutzt fortschrittliche Einzelzelltechnologien, um die Krankheitsmechanismen der ECD zu verstehen. Der Schwerpunkt liegt dabei auf der Identifizierung von Variationen der Tumorzellen und deren Wechselwirkungen in verschiedenen Organen, um umfassendere Behandlungsans\u00e4tze zu entwickeln.<\/p>","protected":false},"author":20,"featured_media":92173,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","cybocfi_hide_featured_image":"","wds_primary_category":0,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[306],"tags":[337],"class_list":["post-42617","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-past-awards","tag-337"],"_links":{"self":[{"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/posts\/42617","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/users\/20"}],"replies":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/comments?post=42617"}],"version-history":[{"count":2,"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/posts\/42617\/revisions"}],"predecessor-version":[{"id":173988,"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/posts\/42617\/revisions\/173988"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/media\/92173"}],"wp:attachment":[{"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/media?parent=42617"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/categories?post=42617"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.erdheim-chester.org\/de\/wp-json\/wp\/v2\/tags?post=42617"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}