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Autoantibodies in Childhood Post-Varicella Acute Cerebellar Ataxia

Published online by Cambridge University Press:  02 December 2014

Coleen Adams ,
Paola Diadori ,
Leeanne Schoenroth  and
Marvin Fritzler
Coleen Adams
Affiliation:
Alberta Children's Hospital and Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
Paola Diadori
Affiliation:
Alberta Children's Hospital and Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
Leeanne Schoenroth
Affiliation:
Alberta Children's Hospital and Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
Marvin Fritzler
Affiliation:
Alberta Children's Hospital and Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
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Abstract

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Background:

Anti-Purkinje cell antibodies have been reported in cerebellar ataxia following Epstein-Barr virus (EBV) infection. We investigated autoantibody responses, including anti-Purkinje cell antibodies, and the clinical course in eight children who developed post-varicella ataxia, five of their siblings with uncomplicated varicella, one child with post-EBV ataxia, two children with acute disseminated encephalomyelitis (ADEM) and one with neuroblastoma associated ataxia, and in age and gender matched controls.

Methods:

Autoantibodies were tested by indirect immunofluorescence (IIF) on cryopreserved cerebrum and cerebellum sections. Other autoantibodies were measured by conventional IIF protocols using HEp-2 cells as a substrate. Antibodies to myelin associated glycoprotein (MAG), asialo-GM1, b2 glycoprotein 1, cardiolipin and myelin basic protein (MBP) were measured by ELISA.

Results:

Three of eight children with acute post-varicella ataxia, one child with post-EBV ataxia, one child with ADEM and one child with uncomplicated varicella, had high titer autoantibodies (<1/160) that reacted with cerebrum and cerebellar tissue. This reactivity was not seen in one child with ADEM, in one with neuroblastoma and ataxia, in the remainder of the children with uncomplicated varicella or age and gender matched controls. Autoantibodies were not seen in CSF from two children with post-varicella ataxia. The punctate staining seen on cerebrum and cerebellum sections co-localized with rabbit antibodies to the centrosome protein pericentrin. All patients with strong reactivity with cerebrum and cerebellar tissue by IIF had elevated levels of anti-MAG that was not confirmed by absorption assay. No reactivity was seen with asialo-GM1, MBP, b2 glycoprotein 1 or cardiolipin. None of the sera had autoantibodies directed against endosomes, the Golgi complex, or the paraneoplastic autoantigens Hu and Yo.

Conclusion:

Some children with post-viral ataxia develop antibodies that have strong reactivity with cerebral and cerebellar tissue. Some of the antigenic reactivity co-localized with the centrosome protein pericentrin.

Résumé:

RÉSUMÉ:Introduction:

Des anticorps dirigés contre les cellules de Purkinje ont été rapportés dans l'ataxie cérébelleuse suite à une infection par le virus d'Epstein-Barr (EBV). Nous avons évalué la réponse immunitaire, incluant les anticorps dirigés contre les cellules de Purkinje, et l'évolution clinique de huit enfants qui ont développé une ataxie suite à la varicelle, cinq membres de leur fratrie qui présentaient une varicelle sans complication, un présentant une ataxie post-EBV et un ayant une ataxie associée à un neu-roblastome.

Méthodes:

Les autoanticorps ont été détectés par immunofluorescence indirecte (IIF) sur des coupes de cerveau et de cervelet congelées. D'autres antoanticorps ont été mesurés par des protocoles IIF conventionnels utilisant des cellules HEp-2 comme substrat. Les anticorps dirigés contre la glycoprotéine associée à la myéline (MAG), l'asialo-GM1, la [32 glycoprotéine 1, la cardiolipine, les protéines basiques de la myéline (PBM) ont été mesurés par ELISA.

Résultats:

Trois des huit enfants ayant présenté une ataxie aiguë suite à la varicelle, un enfant ayant présenté une ataxie post-EBV, un enfant ayant présenté une encéphalomyélite disséminée aiguë (EMDA) et un enfant ayant présenté une varicelle sans complication avaient des titres élevés d'autoanticorps (>1/160) qui réagissaient avec le tissu cérébral et cérébelleux. Cette réactivité n'était pas observée chez un enfant présentant une EMDA, chez un enfant présentant un neuroblastome et une ataxie, chez les enfants présentant une varicelle sans complication et chez des contrôles appariés pour l'âge et le sexe. Les autoanticorps n'ont pas été observés dans le LCR de deux enfants présentant une ataxie suite à la varicelle. La col-oration ponctiforme observée sur les tissus cérébraux et cérébelleux avait la même localisation que les anticorps de lapin dirigés contre la péricentrine, une protéine du centrosome. Tous les patients ayant une forte réactivité avec les tissus cérébraux et cérébelleux par IIF avaient des niveaux élevés d'an-ti-MAG qui n'ont pas été confirmés par un test d'absorption. Aucune réactivité n'a été observée avec l'asialo-GM1, les PBM, la [32 glycoprotéine 1 ou la cardiolipine. Aucun des sérums ne contenait des autoanticorps dirigés contre l'endosome, le complexe de Golgi ou les autoantigènes paranéoplasiques Hu et Yo.

Conclusion:

Certains enfants qui présentent une ataxie post-virale développent des anticorps qui ont une forte affinité pour le tissu cérébral et cérébelleux. Une partie de la réactivité antigénique avait la même localisation que la péricentrine, une protéine du centrosome.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 27 , Issue 4 , November 2000 , pp. 316 - 320
Copyright
Copyright © The Canadian Journal of Neurological Sciences Inc. 2000

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