TY - JOUR
T1 - Monozygotic twins discordant for epilepsy differ in the levels of potentially pathogenic autoantibodies and cytokines
AU - Ganor, Yonatan
AU - Freilinger, Michael
AU - Dulac, Olivier
AU - Levite, Mia
PY - 2005/3
Y1 - 2005/3
N2 - Can autoantibodies (Ab's) and cytokines play a role in epilepsy? Monozygotic twins discordant for epilepsy (most probably Rasmussen's encephalitis (RE)), compared to 49 neurologically intact controls, were both found to contain in their serum (at the time of epilepsy diagnosis) significantly elevated levels of specific Ab's against peptide B (amino acids 372-395) of the ionotropic glutamate receptor of AMPA subtype 3 (i.e. GluR3B peptide). Interestingly, both twins also had clinically elevated levels of Ab's to double-stranded (ds) DNA, glutamic acid decarboxylase, nuclear antigens, β2-glycoprotein I and cardiolipin, as in "classical" autoimmune diseases. Both twins also had significantly elevated levels of IFNγ, TNFα, IL-4 and IL-10 in the serum, compared to the controls. Comparing the twins revealed that the epileptic twin had significantly higher levels of five of the above anti-self Ab's, but significantly lower levels of all four cytokines compared to her healthy sister. Importantly, the epileptic twin, alike three other RE patients tested herein, contained elevated levels of Ab's to GluR3B and dsDNA also in cerebrospinal fluid (CSF) (unavailable of the healthy twin). Our results suggest that the various autoimmune Ab's studied herein, all of which are known already to have a potential to be pathogenic in the nervous system and/or peripheral organs, may play a role in some types of epilepsy. The titer of such Ab's and of key cytokines may be crucial for either facilitating or arresting the development of epilepsy. Our findings also show that anti-GluR3B Ab's in serum are not necessarily detrimental (their presence in the CSF may be more dangerous), and that they are not a mere side effect of already existing epilepsy, as they were found herein in serum of a healthy individual. These findings and suggestions may be of clinical importance and call for further studies.
AB - Can autoantibodies (Ab's) and cytokines play a role in epilepsy? Monozygotic twins discordant for epilepsy (most probably Rasmussen's encephalitis (RE)), compared to 49 neurologically intact controls, were both found to contain in their serum (at the time of epilepsy diagnosis) significantly elevated levels of specific Ab's against peptide B (amino acids 372-395) of the ionotropic glutamate receptor of AMPA subtype 3 (i.e. GluR3B peptide). Interestingly, both twins also had clinically elevated levels of Ab's to double-stranded (ds) DNA, glutamic acid decarboxylase, nuclear antigens, β2-glycoprotein I and cardiolipin, as in "classical" autoimmune diseases. Both twins also had significantly elevated levels of IFNγ, TNFα, IL-4 and IL-10 in the serum, compared to the controls. Comparing the twins revealed that the epileptic twin had significantly higher levels of five of the above anti-self Ab's, but significantly lower levels of all four cytokines compared to her healthy sister. Importantly, the epileptic twin, alike three other RE patients tested herein, contained elevated levels of Ab's to GluR3B and dsDNA also in cerebrospinal fluid (CSF) (unavailable of the healthy twin). Our results suggest that the various autoimmune Ab's studied herein, all of which are known already to have a potential to be pathogenic in the nervous system and/or peripheral organs, may play a role in some types of epilepsy. The titer of such Ab's and of key cytokines may be crucial for either facilitating or arresting the development of epilepsy. Our findings also show that anti-GluR3B Ab's in serum are not necessarily detrimental (their presence in the CSF may be more dangerous), and that they are not a mere side effect of already existing epilepsy, as they were found herein in serum of a healthy individual. These findings and suggestions may be of clinical importance and call for further studies.
KW - Autoantibodies
KW - Cytokines
KW - Epilepsy twins
KW - Glutamate receptor GluR3
KW - Rasmussen's encephalitis
UR - http://www.scopus.com/inward/record.url?scp=21044434795&partnerID=8YFLogxK
U2 - 10.1080/08916930500100825
DO - 10.1080/08916930500100825
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C2 - 16040334
AN - SCOPUS:21044434795
SN - 0891-6934
VL - 38
SP - 139
EP - 150
JO - Autoimmunity
JF - Autoimmunity
IS - 2
ER -