PMID- 34904712
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20220722
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 63
IP  - 2
DP  - 2022 Feb
TI  - Increased expression of complement components in tuberous sclerosis complex and 
      focal cortical dysplasia type 2B brain lesions.
PG  - 364-374
LID - 10.1111/epi.17139 [doi]
AB  - OBJECTIVE: Increasing evidence supports the contribution of inflammatory 
      mechanisms to the neurological manifestations of epileptogenic developmental 
      pathologies linked to mammalian target of rapamycin (mTOR) pathway dysregulation 
      (mTORopathies), such as tuberous sclerosis complex (TSC) and focal cortical 
      dysplasia (FCD). In this study, we aimed to investigate the expression pattern 
      and cellular distribution of the complement factors C1q and C3 in resected 
      cortical tissue of clinically well-characterized patients with TSC and FCD2B. 
      METHODS: We applied immunohistochemistry in TSC (n = 29) and FCD2B (n = 32) 
      samples and compared them to autopsy and biopsy controls (n = 27). Furthermore, 
      protein expression was observed via Western blot, and for descriptive 
      colocalization studies immunofluorescence double labeling was performed. RESULTS: 
      Protein expression for C3 was significantly upregulated in TSC and FCD2B white 
      and gray matter lesions compared to controls. Staining of the synaptic vesicle 
      protein synaptophysin showed a remarkable increase in the white matter of both 
      TSC and FCD2B. Furthermore, confocal imaging revealed colocalization of 
      complement factors with astroglial, microglial, neuronal, and abnormal cells in 
      various patterns. SIGNIFICANCE: Our results demonstrate that the prominent 
      activation of the complement pathway represents a common pathological hallmark of 
      TSC and FCD2B, suggesting that complement overactivation may play a role in these 
      mTORopathies.
CI  - (c) 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of 
      International League Against Epilepsy.
FAU - Gruber, Victoria-Elisabeth
AU  - Gruber VE
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - Luinenburg, Mark J
AU  - Luinenburg MJ
AD  - Department of (Neuro)Pathology, Amsterdam University Medical Center, University 
      of Amsterdam, Amsterdam, the Netherlands.
FAU - Colleselli, Katrin
AU  - Colleselli K
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - Endmayr, Verena
AU  - Endmayr V
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Anink, Jasper J
AU  - Anink JJ
AD  - Department of (Neuro)Pathology, Amsterdam University Medical Center, University 
      of Amsterdam, Amsterdam, the Netherlands.
FAU - Zimmer, Till S
AU  - Zimmer TS
AD  - Department of (Neuro)Pathology, Amsterdam University Medical Center, University 
      of Amsterdam, Amsterdam, the Netherlands.
FAU - Jansen, Floor
AU  - Jansen F
AD  - Department of Child Neurology, Brain Center, University Medical Center Utrecht, 
      Member of the European Reference Network EpiCARE, Utrecht, the Netherlands.
FAU - Gosselaar, Peter
AU  - Gosselaar P
AD  - Department of Neurosurgery, University Medical Center Utrecht, Utrecht, the 
      Netherlands.
FAU - Coras, Roland
AU  - Coras R
AD  - Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.
FAU - Scholl, Theresa
AU  - Scholl T
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - Blumcke, Ingmar
AU  - Blumcke I
AUID- ORCID: 0000-0001-8676-0788
AD  - Department of Neuropathology, University Hospital Erlangen, Erlangen, Germany.
FAU - Pimentel, Jose
AU  - Pimentel J
AD  - Department of Neurology, Santa Maria Hospital, Lisbon, Portugal.
FAU - Hainfellner, Johannes A
AU  - Hainfellner JA
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Hoftberger, Romana
AU  - Hoftberger R
AD  - Division of Neuropathology and Neurochemistry, Department of Neurology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Rossler, Karl
AU  - Rossler K
AD  - Department of Neurosurgery, Medical University of Vienna, Vienna, Austria.
FAU - Feucht, Martha
AU  - Feucht M
AUID- ORCID: 0000-0001-7691-8158
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - van Scheppingen, Jackelien
AU  - van Scheppingen J
AD  - Department of (Neuro)Pathology, Amsterdam University Medical Center, University 
      of Amsterdam, Amsterdam, the Netherlands.
FAU - Aronica, Eleonora
AU  - Aronica E
AD  - Department of (Neuro)Pathology, Amsterdam University Medical Center, University 
      of Amsterdam, Amsterdam, the Netherlands.
AD  - Epilepsy Institutes of the Netherlands Foundation, Heemstede, the Netherlands.
FAU - Muhlebner, Angelika
AU  - Muhlebner A
AUID- ORCID: 0000-0001-9102-7353
AD  - Department of (Neuro)Pathology, Amsterdam University Medical Center, University 
      of Amsterdam, Amsterdam, the Netherlands.
AD  - Department of Pathology, University Medical Center Utrecht, Utrecht, the 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211214
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
SB  - IM
MH  - Brain/pathology
MH  - *Epilepsy/pathology
MH  - Humans
MH  - *Malformations of Cortical Development/complications/diagnostic 
      imaging/metabolism
MH  - Neurons/pathology
MH  - *Tuberous Sclerosis/complications/pathology
PMC - PMC9299842
OTO - NOTNLM
OT  - complement
OT  - cortical development
OT  - epilepsy
OT  - focal cortical dysplasia
OT  - inflammation
OT  - tuberous sclerosis complex
COIS- None of the authors has any conflict of interest to disclose. We confirm that we 
      have read the Journal's position on issues involved in ethical publication and 
      affirm that this report is consistent with those guidelines.
EDAT- 2021/12/15 06:00
MHDA- 2022/04/21 06:00
PMCR- 2022/07/20
CRDT- 2021/12/14 09:48
PHST- 2021/11/15 00:00 [revised]
PHST- 2021/05/21 00:00 [received]
PHST- 2021/11/16 00:00 [accepted]
PHST- 2021/12/15 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2021/12/14 09:48 [entrez]
PHST- 2022/07/20 00:00 [pmc-release]
AID - EPI17139 [pii]
AID - 10.1111/epi.17139 [doi]
PST - ppublish
SO  - Epilepsia. 2022 Feb;63(2):364-374. doi: 10.1111/epi.17139. Epub 2021 Dec 14.