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Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia.

Fritzler MJ, Zhang M, Stinton LM, Rattner JB - BMC Pediatr (2003)

Bottom Line: Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells.IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells.This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Faculty of Medicine University of Calgary, 3330 Hospital Dr, NW, Calgary, AB T2N 4N1, Canada. fritzler@ucalgary.ca

ABSTRACT

Background: Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: gammagamma-enolase, pericentrin, ninein, PCM-1, and Mob1.

Methods: Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV) ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF) using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL) were detected by ELISA.

Results: Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls.

Conclusion: This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin.

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Reactivity of rabbit antibodies to pericentrim on monkey cerebellum Indirect immunofluorescence of monkey cerebellum stained with rabbit antibodies to pericentrin (b,d). Cells believed to be Bergman glial cells (a,b) and an adjacent Purkinje cell (c,d) show intense staining of centrosomes. The nuclei of the reactive cells are counterstained with DAPI (a,c). Axonal staining by anti-pericentrin is observed as strands (b,d).
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Figure 4: Reactivity of rabbit antibodies to pericentrim on monkey cerebellum Indirect immunofluorescence of monkey cerebellum stained with rabbit antibodies to pericentrin (b,d). Cells believed to be Bergman glial cells (a,b) and an adjacent Purkinje cell (c,d) show intense staining of centrosomes. The nuclei of the reactive cells are counterstained with DAPI (a,c). Axonal staining by anti-pericentrin is observed as strands (b,d).

Mentions: Since unique reactivity with pericentrin was noted, we proceeded to determine the distribution of pericentrin in cerebellum tissue by IIF. We observed that pericentrin is expressed in cerebellum as evidenced by intense staining of centrosomes and less intense staining of neuronal axons (Figures 3,4). Cells stained by human sera and rabbit antibodies to pericentrin were found throughout the cerebellum including those in the nuclear and granular layers. This observation is consistent with evidence that, in addition to it being a component of centrosomes, pericentrin exists as particles in the cytoplasm [12]. We observed that some cells, particularly certain Purkinje cells, contain numerous particles and more than one centrosome (Figure 3) and strong reactivity was also found in adjacent cells that were consistent with the location and appearance of Bergman glial cells (Figure 4). These observations are consistent with earlier observations that Purkinje cells are polyploidy [32,33]. The observation that children with ataxia produce antibodies to centrosome proteins, including pericentrin, and that Purkinje cells are polyploid raises the question of the vulnerability of these cells to autoimmune attack. Although we have no direct evidence to substantiate this hypothesis, in paraneoplastic cerebellar degeneration where ataxia is a dominant clinical feature, anti-Purkinje cell antibodies (APCA or anti-Yo) are believed to be responsible for the Purkinje cell loss that accompanies the disease [34,35]. This is supported by observations that removal of the autoantibodies from the circulation of a paraneoplastic cerebellar degeneration patient provided improvement of cerebellar signs [36].


Spectrum of centrosome autoantibodies in childhood varicella and post-varicella acute cerebellar ataxia.

Fritzler MJ, Zhang M, Stinton LM, Rattner JB - BMC Pediatr (2003)

Reactivity of rabbit antibodies to pericentrim on monkey cerebellum Indirect immunofluorescence of monkey cerebellum stained with rabbit antibodies to pericentrin (b,d). Cells believed to be Bergman glial cells (a,b) and an adjacent Purkinje cell (c,d) show intense staining of centrosomes. The nuclei of the reactive cells are counterstained with DAPI (a,c). Axonal staining by anti-pericentrin is observed as strands (b,d).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC222907&req=5

Figure 4: Reactivity of rabbit antibodies to pericentrim on monkey cerebellum Indirect immunofluorescence of monkey cerebellum stained with rabbit antibodies to pericentrin (b,d). Cells believed to be Bergman glial cells (a,b) and an adjacent Purkinje cell (c,d) show intense staining of centrosomes. The nuclei of the reactive cells are counterstained with DAPI (a,c). Axonal staining by anti-pericentrin is observed as strands (b,d).
Mentions: Since unique reactivity with pericentrin was noted, we proceeded to determine the distribution of pericentrin in cerebellum tissue by IIF. We observed that pericentrin is expressed in cerebellum as evidenced by intense staining of centrosomes and less intense staining of neuronal axons (Figures 3,4). Cells stained by human sera and rabbit antibodies to pericentrin were found throughout the cerebellum including those in the nuclear and granular layers. This observation is consistent with evidence that, in addition to it being a component of centrosomes, pericentrin exists as particles in the cytoplasm [12]. We observed that some cells, particularly certain Purkinje cells, contain numerous particles and more than one centrosome (Figure 3) and strong reactivity was also found in adjacent cells that were consistent with the location and appearance of Bergman glial cells (Figure 4). These observations are consistent with earlier observations that Purkinje cells are polyploidy [32,33]. The observation that children with ataxia produce antibodies to centrosome proteins, including pericentrin, and that Purkinje cells are polyploid raises the question of the vulnerability of these cells to autoimmune attack. Although we have no direct evidence to substantiate this hypothesis, in paraneoplastic cerebellar degeneration where ataxia is a dominant clinical feature, anti-Purkinje cell antibodies (APCA or anti-Yo) are believed to be responsible for the Purkinje cell loss that accompanies the disease [34,35]. This is supported by observations that removal of the autoantibodies from the circulation of a paraneoplastic cerebellar degeneration patient provided improvement of cerebellar signs [36].

Bottom Line: Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells.IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells.This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Faculty of Medicine University of Calgary, 3330 Hospital Dr, NW, Calgary, AB T2N 4N1, Canada. fritzler@ucalgary.ca

ABSTRACT

Background: Sera from children with post-varicella infections have autoantibodies that react with centrosomes in brain and tissue culture cells. We investigated the sera of children with infections and post-varicella ataxia and related conditions for reactivity to five recombinant centrosome proteins: gammagamma-enolase, pericentrin, ninein, PCM-1, and Mob1.

Methods: Sera from 12 patients with acute post-varicella ataxia, 1 with post-Epstein Barr virus (EBV) ataxia, 5 with uncomplicated varicella infections, and other conditions were tested for reactivity to cryopreserved cerebellum tissue and recombinant centrosome proteins. The distribution of pericentrin in the cerebellum was studied by indirect immunofluorescence (IIF) using rabbit antibodies to the recombinant protein. Antibodies to phospholipids (APL) were detected by ELISA.

Results: Eleven of 12 children with post-varicella ataxia, 4/5 children with uncomplicated varicella infections, 1/1 with post-EBV ataxia, 2/2 with ADEM, 1/2 with neuroblastoma and ataxia, and 2/2 with cerebellitis had antibodies directed against 1 or more recombinant centrosome antigens. Antibodies to pericentrin were seen in 5/12 children with post-varicella ataxia but not in any of the other sera tested. IIF demonstrated that pericentrin is located in axons and centrosomes of cerebellar cells. APL were detected in 75% of the sera from children with post-varicella ataxia and 50% of children with varicella without ataxia and in none of the controls.

Conclusion: This is the first study to show the antigen specificity of anti-centrosome antibodies in children with varicella. Our data suggest that children with post-varicella ataxia have unique autoantibody reactivity to pericentrin.

Show MeSH
Related in: MedlinePlus