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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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Autoantibodies to centrosomes Indirect immunofluorescence illustrating antibodies to centrosomes as seen in sera of children with post-varicella ataxia on formalin fixed HeLa cell substrate. The cells are counterstained with DAPI to identify the nucleus (a) and the pattern of staining and localization of centrosomes (arrows) is shown in panel b. Original magnification ×400.
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Figure 1: Autoantibodies to centrosomes Indirect immunofluorescence illustrating antibodies to centrosomes as seen in sera of children with post-varicella ataxia on formalin fixed HeLa cell substrate. The cells are counterstained with DAPI to identify the nucleus (a) and the pattern of staining and localization of centrosomes (arrows) is shown in panel b. Original magnification ×400.

Mentions: Eleven of 12 sera from children with post-varicella ataxia had IgG antibodies that reacted with the centrosome of formalin-fixed HeLa cells in an IIF assay (Figure 1). We observed that commercially prepared substrates, such as HEp-2 cells, were not sensitive for the detection of centrosome autoantibodies but that the formalin-fixed HeLa cells are a more reliable and sensitive substrate. When the sera were tested for IgG antibodies by immunoblotting (Figure 2), 10/12 reacted with at least one of the five centrosome proteins: ninein, PCM 1, γγ-enolase, Mob-1, or pericentrin (Table 1). Thus, one serum had autoantibodies to a centrosome antigen that was not included in the proteins listed above. Specifically, 5/12 (42%) reacted with pericentrin (Figure 2), 3/12 (25%) with ninein, 6/12 (50%) with PCM 1, 3/12 (25%) with Mob-1, and 3/11 (27%) with γγ-enolase. By comparison, 3/5 siblings with varicella infections but no ataxia, 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 at least one of the centrosome proteins. None of the 12 sera from other disease groups, including 20 children with juvenile chronic arthritis, or 20 normal controls reacted with pericentrin, although they did react with other recombinant centrosome proteins. When convalescent sera were tested, the frequency of anti-centrosome antibodies as detected by IIF and anti-pericentrin as detected by immunoblotting decreased to 4/12 (33%) of children with post-varicella ataxia, and none of the other children sustained detectable reactivity at two weeks follow-up. The number of sera from children with ataxia that was not associated with varicella is admittedly small and validation of our data would require multi-center studies or access to large neurological or infectious diseases serum banks.


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

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

Autoantibodies to centrosomes Indirect immunofluorescence illustrating antibodies to centrosomes as seen in sera of children with post-varicella ataxia on formalin fixed HeLa cell substrate. The cells are counterstained with DAPI to identify the nucleus (a) and the pattern of staining and localization of centrosomes (arrows) is shown in panel b. Original magnification ×400.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC222907&req=5

Figure 1: Autoantibodies to centrosomes Indirect immunofluorescence illustrating antibodies to centrosomes as seen in sera of children with post-varicella ataxia on formalin fixed HeLa cell substrate. The cells are counterstained with DAPI to identify the nucleus (a) and the pattern of staining and localization of centrosomes (arrows) is shown in panel b. Original magnification ×400.
Mentions: Eleven of 12 sera from children with post-varicella ataxia had IgG antibodies that reacted with the centrosome of formalin-fixed HeLa cells in an IIF assay (Figure 1). We observed that commercially prepared substrates, such as HEp-2 cells, were not sensitive for the detection of centrosome autoantibodies but that the formalin-fixed HeLa cells are a more reliable and sensitive substrate. When the sera were tested for IgG antibodies by immunoblotting (Figure 2), 10/12 reacted with at least one of the five centrosome proteins: ninein, PCM 1, γγ-enolase, Mob-1, or pericentrin (Table 1). Thus, one serum had autoantibodies to a centrosome antigen that was not included in the proteins listed above. Specifically, 5/12 (42%) reacted with pericentrin (Figure 2), 3/12 (25%) with ninein, 6/12 (50%) with PCM 1, 3/12 (25%) with Mob-1, and 3/11 (27%) with γγ-enolase. By comparison, 3/5 siblings with varicella infections but no ataxia, 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 at least one of the centrosome proteins. None of the 12 sera from other disease groups, including 20 children with juvenile chronic arthritis, or 20 normal controls reacted with pericentrin, although they did react with other recombinant centrosome proteins. When convalescent sera were tested, the frequency of anti-centrosome antibodies as detected by IIF and anti-pericentrin as detected by immunoblotting decreased to 4/12 (33%) of children with post-varicella ataxia, and none of the other children sustained detectable reactivity at two weeks follow-up. The number of sera from children with ataxia that was not associated with varicella is admittedly small and validation of our data would require multi-center studies or access to large neurological or infectious diseases serum banks.

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