Differential expression of major histocompatibility complex class I in developmental glioneuronal lesions

Wim Gm Spliet,Eleonora Aronica,Jasper J Anink,Peter C Van Rijen,Avanita S Prabowo,Anand M Iyer

doi:10.1186/1742-2094-10-12

Abstract

PurposeThe expression of the major histocompatibility complex class I (MHC-I) in the brain has received considerable interest not only because of its fundamental role in the immune system, but also for its non-immune functions in the context of activity-dependent brain development and plasticity.MethodsIn the present study we evaluated the expression and cellular pattern of MHC-I in focal glioneuronal lesions associated with intractable epilepsy. MHC-I expression was studied in epilepsy surgery cases with focal cortical dysplasia (FCD I, n = 6; FCD IIa, n = 6 and FCD IIb, n = 15), tuberous sclerosis complex (TSC, cortical tubers; n = 6) or ganglioglioma (GG; n = 15) using immunocytochemistry. Evaluation of T lymphocytes with granzyme-B+ granules and albumin immunoreactivity was also performed.ResultsAll lesions were characterized by MHC-I expression in blood vessels. Expression in both endothelial and microglial cells as well as in neurons (dysmorphic/dysplastic neurons) was observed in FCD II, TSC and GG cases. We observed perivascular and parenchymal T lymphocytes (CD8+, T-cytotoxic) with granzyme-B+ granules in FCD IIb and TSC specimens. Albumin extravasation, with uptake in astrocytes, was observed in FCD IIb and GG cases.ConclusionsOur findings indicate a prominent upregulation of MHC-I as part of the immune response occurring in epileptogenic glioneuronal lesions. In particular, the induction of MHC-I in neuronal cells appears to be a feature of type II FCD, TSC and GG and may represent an important accompanying event of the immune response, associated with blood–brain barrier dysfunction, in these developmental lesions.

Highlights

Recent clinical and neuropathological evidence supports the critical role of a sustained inflammatory reaction in glioneuronal lesions with activation of both the innate and the adaptive immune response and involvement of different inflammatory pathways
According to the current histopathological classification system [5], focal cortical dysplasia (FCD) has been classified into type I, characterized by cortical dyslamination, and type II, characterized by additional cytological abnormalities (FCD IIa with dysmorphic neurons and FCD IIb with dysmorphic neurons and balloon cells)
In a recent study [6], we confirmed the occurrence of complex inflammatory changes in FCD specimens and demonstrated that the severity of these changes is greater in FCD IIb than in specimens from patients with FCD I

Summary

Introduction

Recent clinical and neuropathological evidence supports the critical role of a sustained inflammatory reaction in glioneuronal lesions with activation of both the innate and the adaptive immune response and involvement of different inflammatory pathways (for reviews see [1,2,3,4]). In a recent study [6], we confirmed the occurrence of complex inflammatory changes (involving both glial and neuronal cells) in FCD specimens and demonstrated that the severity of these changes is greater in FCD IIb than in specimens from patients with FCD I. The activation of components of the adaptive immunity, with the presence of T lymphocytes (CD8+, T-cytotoxic/suppressor immunophenotype), has been mainly observed in FCD IIb specimens [6]. Whether these inflammatory changes represent a feature common to different developmental glioneuronal lesions and whether induction of major histocompatibility complex (MHC) class I molecules may be involved still needs to be clarified

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