Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex.
Cortical tubers and subependymal giant cell tumors (SGCT) are two major cerebral lesions associated with tuberous sclerosis complex (TSC). In the present study, we investigated immunocytochemically the inflammatory cell components and the induction of two major pro-inflammatory pathways (the interleukin (IL)-1beta and complement pathways) in tubers and SGCT resected from TSC patients. All lesions were characterized by the prominent presence of microglial cells expressing class II-antigens (HLA-DR) and, to a lesser extent, the presence of CD68-positive macrophages. We also observed perivascular and parenchymal T lymphocytes (CD3(+)) with a predominance of CD8(+) T-cytotoxic/suppressor lymphoid cells. Activated microglia and reactive astrocytes expressed IL-1beta and its signaling receptor IL-1RI, as well as components of the complement cascade, such as C1q, C3c and C3d. Albumin extravasation, with uptake in astrocytes, was observed in both tubers and SGCT, suggesting that alterations in blood brain barrier permeability are associated with inflammation in TSC-associated lesions. Our findings demonstrate a persistent and complex activation of inflammatory pathways in cortical tubers and SGCT.
Boer
K
K
Department of (Neuro)Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
Jansen
F
F
Nellist
M
M
Redeker
S
S
van den Ouweland
A M W
AM
Spliet
W G M
WG
van Nieuwenhuizen
O
O
Troost
D
D
Crino
P B
PB
Aronica
E
E
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001932:Brain Neoplasms / Q000150:complications*; D017252:CD3 Complex / Q000378:metabolism; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005870:Giant Cell Tumors / Q000150:complications*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000209:etiology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000150:complications*; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D005904:Glial Fibrillary Acidic Protein; D006684:HLA-DR Antigens; D053583:Interleukin-1beta; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule