Buster Posted August 15, 2009 Report Posted August 15, 2009 if you can't see the replies in this thread, set the options button to standard rather than outline. Try this link for an explanation of ASO and AntiDNAse B http://www.latitudes.org/forums/index.php?...ost&p=25312 Just as a quick reminder, PANDAS is not thought to be caused by ASO or Anti-DNAseB, but is thought to be caused by another antibody known as 24.3.1 (great name huh). 24.3.1 showed up in the kids who had PANDAS in Swedo's studies and was not elevated in controls. ASO and anti-DNAse B showed up in both PANDAS and controls. However, ASO and Anti-DNAse B was elevated in PANDAS kids with sudden CY-BOCS score exacerbation. The 24.3.1 gives a new differential between the PANDAS kids and the controls. I say "thought to be caused" because causality is still not yet shown. There could be yet another antibody/protein not yet found or perhaps the antibody doesn't matter until something else opens the blood brain barrier. So, what is the usefulness of ASO and Anti-DNAse B? Well, I don't think there is much use (especially since PANDAS exacerbations seem to happen when the blood-brain barrier is disturbed and not just when a child gets strep). However, given the educational state of doctors, having a rising ASO or antiDNAse B sure helps convince them -- since they don't seem to read the research papers :-) The emphasis on ASO and Anti-DNAse B is largely because of Swedos original study where she only selected kids with rising ASO and AntiDNAse B as opposed to kids with just positive throat cultures. Swedo's study chose to use a strong definition of "associated with strep" which was to define "associated with strep" as "immunologic response to known strep antigens". The discovery of 24.3.1 wasn't until 2004 (8 years after Swedo's study). 24.3.1 is thought to be an unusual antibody response to a strep antigen that isn't suppressed in kids with PANDAS (i.e., others seem to suppress 24.3.1) -- I think this is why IVIG might work. It is unknown what the rate of fall is for ASO or AntiDNAse B or for the PANDAS antibody 24.3.1. The current research by Kirvan/Cunningham indicate that the concentration of 24.3.1 is important and so its rate of fall matters. There is some evidence that CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) . Hope this and the above reference help. Regards, Buster Sorry, sometimes I get lost with all the lingo as I am trying to absorb!! Forgive me for confusing the two and Thank you so much for clarifying!! Dr K said the tests would tell him if she had had strep in the last YEAR though!!!
T_Mom Posted August 15, 2009 Report Posted August 15, 2009 ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
Buster Posted August 16, 2009 Author Report Posted August 16, 2009 Hi T.Mom, On the evidence that 24.3.1 falls at same rate as other two antibodies. There are essentially three elements: Swedo showed that system exacerbations tracked ASO titers for those PANDAS kids that had ASO response Kirvan showed that CaM Kinase II activation was substantially reduced in convalescent serum (see fig 3a in http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf) finally, Kirvan showed that antibody 24.3.1 activated Cam Kinase II (see figure 4a in http://www.pandasnetwork.org/Cunningham.NMpaper%5b1%5d.pdf) What's interesting about fig 3a in the JNI paper is that 25% of the kids did not have a substantial change in their CaM Kinase II -- to me this indicates that perhaps their blood brain barrier closed rather than the antibody going away -- however, that's just conjecture. Okay, so what is CaM Kinase II, well, that's a tough topic. Let's see if a short answer works: Upon activation, CaM Kinase II turns on glutamate receptors on synapses. This changes the electrical property of the synapse. So if CaM Kinase II is happening incorrectly, it interferes with how the synapse works -- sort of like interference on a radio. So, if 24.3.1 causes CaM Kinase II activation, then if it crosses the blood-brain barrier, it could be causing incorrect signalling in the region of the brain sensitive to lysogangliosides and glutomate signalling (namely the basal ganglia). I realize that is 3 if's in a row, but that's about as far as the research has gotten. Hope that helps -- I can point you to papers if you really want details, Regards, Buster ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
T_Mom Posted August 16, 2009 Report Posted August 16, 2009 Thank you Buster-- I have read your post twice now and believe I am getting a glimmer of the essence of what you are saying:) If you have a few refs. handy on this issue perhaps it would help me, (and hopefully others) to understand more on this -- Thank you so very much-- TMom
peglem Posted August 16, 2009 Report Posted August 16, 2009 So why isn't Cunningham testing for 24.3.1 w/ her study? I'm trying to make sense of all of this. My daughter's CaM KinaseII was in the SC range, but antilysoganglioside was not elevated. The only other elevation she had was the anti D2...does that mean she's convalescent? And I keep wondering if the blood levels correlate to brain levels? This is so confusing! Hi T.Mom, On the evidence that 24.3.1 falls at same rate as other two antibodies. There are essentially three elements: Swedo showed that system exacerbations tracked ASO titers for those PANDAS kids that had ASO response Kirvan showed that CaM Kinase II activation was substantially reduced in convalescent serum (see fig 3a in http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf) finally, Kirvan showed that antibody 24.3.1 activated Cam Kinase II (see figure 4a in http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf) What's interesting about fig 3a in the JNI paper is that 25% of the kids did not have a substantial change in their CaM Kinase II -- to me this indicates that perhaps their blood brain barrier closed rather than the antibody going away -- however, that's just conjecture. Okay, so what is CaM Kinase II, well, that's a tough topic. Let's see if a short answer works: Upon activation, CaM Kinase II turns on glutamate receptors on synapses. This changes the electrical property of the synapse. So if CaM Kinase II is happening incorrectly, it interferes with how the synapse works -- sort of like interference on a radio. So, if 24.3.1 causes CaM Kinase II activation, then if it crosses the blood-brain barrier, it could be causing incorrect signalling in the region of the brain sensitive to lysogangliosides and glutomate signalling (namely the basal ganglia). I realize that is 3 if's in a row, but that's about as far as the research has gotten. Hope that helps -- I can point you to papers if you really want details, Regards, Buster ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
Buster Posted August 16, 2009 Author Report Posted August 16, 2009 Actually Cunningham is testing for 24.3.1 but only under the general category of anti-lysogangliosides (i.e., she's looking at competitive inhibition but is using the whole serum -- she's not isolating the antibody first). This is likely a cost issue. I'd imagine isolating the antibody would be quite expensive. The presumption is that the anti-lysogangliosides found in competitive inhibition are the 24.3.1, 31.1.1 and 37.2.1. Of these 24.3.1 is the only one that seems to really drive CaM Kinase II. So I suppose your question is "if the anti-lysogangliosides are low, why is her CaM Kinase II high?" Frankly, I'm not sure. CaM Kinase II can stay active for a while, but it is surprising that it's remaining high. I would have expected the anti-lysogangliosides to be elevated if the CaM Kinase II is activated. I guess that's the whole purpose of the current study. It may mean there is another cause. In terms of blood level and brain level, it looks like this is only correlated during an exacerbation. The nature paper reports CSF and Serum levels and these correlate in exacerbations. Hence the thought that there's a BBB problem. Regards, Buster So why isn't Cunningham testing for 24.3.1 w/ her study? I'm trying to make sense of all of this. My daughter's CaM KinaseII was in the SC range, but antilysoganglioside was not elevated. The only other elevation she had was the anti D2...does that mean she's convalescent? And I keep wondering if the blood levels correlate to brain levels? This is so confusing! Hi T.Mom, On the evidence that 24.3.1 falls at same rate as other two antibodies. There are essentially three elements: Swedo showed that system exacerbations tracked ASO titers for those PANDAS kids that had ASO response Kirvan showed that CaM Kinase II activation was substantially reduced in convalescent serum (see fig 3a in http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf) finally, Kirvan showed that antibody 24.3.1 activated Cam Kinase II (see figure 4a in http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf) What's interesting about fig 3a in the JNI paper is that 25% of the kids did not have a substantial change in their CaM Kinase II -- to me this indicates that perhaps their blood brain barrier closed rather than the antibody going away -- however, that's just conjecture. Okay, so what is CaM Kinase II, well, that's a tough topic. Let's see if a short answer works: Upon activation, CaM Kinase II turns on glutamate receptors on synapses. This changes the electrical property of the synapse. So if CaM Kinase II is happening incorrectly, it interferes with how the synapse works -- sort of like interference on a radio. So, if 24.3.1 causes CaM Kinase II activation, then if it crosses the blood-brain barrier, it could be causing incorrect signalling in the region of the brain sensitive to lysogangliosides and glutomate signalling (namely the basal ganglia). I realize that is 3 if's in a row, but that's about as far as the research has gotten. Hope that helps -- I can point you to papers if you really want details, Regards, Buster ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
peglem Posted August 16, 2009 Report Posted August 16, 2009 I just had another look at her results. The anti-lysoganglioside is higher than the negative control #, (at 120mins.=160, the neg. control # is 80). Same thing with the anti-tubulin, at 120mins.=500, whereas neg. control is 250). I don't think my daughter has had a real exacerbation in over a year(since starting prophylactic zith), but her baseline is not so great, so its hard to say. So, does that mean she does show some elevation? Actually Cunningham is testing for 24.3.1 but only under the general category of anti-lysogangliosides (i.e., she's looking at competitive inhibition but is using the whole serum -- she's not isolating the antibody first). This is likely a cost issue. I'd imagine isolating the antibody would be quite expensive. The presumption is that the anti-lysogangliosides found in competitive inhibition are the 24.3.1, 31.1.1 and 37.2.1. Of these 24.3.1 is the only one that seems to really drive CaM Kinase II. So I suppose your question is "if the anti-lysogangliosides are low, why is her CaM Kinase II high?" Frankly, I'm not sure. CaM Kinase II can stay active for a while, but it is surprising that it's remaining high. I would have expected the anti-lysogangliosides to be elevated if the CaM Kinase II is activated. I guess that's the whole purpose of the current study. It may mean there is another cause. In terms of blood level and brain level, it looks like this is only correlated during an exacerbation. The nature paper reports CSF and Serum levels and these correlate in exacerbations. Hence the thought that there's a BBB problem. Regards, Buster So why isn't Cunningham testing for 24.3.1 w/ her study? I'm trying to make sense of all of this. My daughter's CaM KinaseII was in the SC range, but antilysoganglioside was not elevated. The only other elevation she had was the anti D2...does that mean she's convalescent? And I keep wondering if the blood levels correlate to brain levels? This is so confusing! Hi T.Mom, On the evidence that 24.3.1 falls at same rate as other two antibodies. There are essentially three elements: Swedo showed that system exacerbations tracked ASO titers for those PANDAS kids that had ASO response Kirvan showed that CaM Kinase II activation was substantially reduced in convalescent serum (see fig 3a in http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf) finally, Kirvan showed that antibody 24.3.1 activated Cam Kinase II (see figure 4a in http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf) What's interesting about fig 3a in the JNI paper is that 25% of the kids did not have a substantial change in their CaM Kinase II -- to me this indicates that perhaps their blood brain barrier closed rather than the antibody going away -- however, that's just conjecture. Okay, so what is CaM Kinase II, well, that's a tough topic. Let's see if a short answer works: Upon activation, CaM Kinase II turns on glutamate receptors on synapses. This changes the electrical property of the synapse. So if CaM Kinase II is happening incorrectly, it interferes with how the synapse works -- sort of like interference on a radio. So, if 24.3.1 causes CaM Kinase II activation, then if it crosses the blood-brain barrier, it could be causing incorrect signalling in the region of the brain sensitive to lysogangliosides and glutomate signalling (namely the basal ganglia). I realize that is 3 if's in a row, but that's about as far as the research has gotten. Hope that helps -- I can point you to papers if you really want details, Regards, Buster ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
Buster Posted August 16, 2009 Author Report Posted August 16, 2009 We probably should have pulled this out to its own thread, ... I agree with you that your anti-lysogangliosides are pretty close to the negative controls. There are a couple of possibilities: a ) azithromycin is having an effect on the results -- there are papers that indicate macrolides affect the distribution of the components of CaM Kinase II b ) there's some other element driving elevated CaM Kinase II Did Cunningham offer any more details? Certainly unclear to me how to read those results. Regards, Buster I just had another look at her results. The anti-lysoganglioside is higher than the negative control #, (at 120mins.=160, the neg. control # is 80). Same thing with the anti-tubulin, at 120mins.=500, whereas neg. control is 250). I don't think my daughter has had a real exacerbation in over a year(since starting prophylactic zith), but her baseline is not so great, so its hard to say. So, does that mean she does show some elevation?Actually Cunningham is testing for 24.3.1 but only under the general category of anti-lysogangliosides (i.e., she's looking at competitive inhibition but is using the whole serum -- she's not isolating the antibody first). This is likely a cost issue. I'd imagine isolating the antibody would be quite expensive. The presumption is that the anti-lysogangliosides found in competitive inhibition are the 24.3.1, 31.1.1 and 37.2.1. Of these 24.3.1 is the only one that seems to really drive CaM Kinase II. So I suppose your question is "if the anti-lysogangliosides are low, why is her CaM Kinase II high?" Frankly, I'm not sure. CaM Kinase II can stay active for a while, but it is surprising that it's remaining high. I would have expected the anti-lysogangliosides to be elevated if the CaM Kinase II is activated. I guess that's the whole purpose of the current study. It may mean there is another cause. In terms of blood level and brain level, it looks like this is only correlated during an exacerbation. The nature paper reports CSF and Serum levels and these correlate in exacerbations. Hence the thought that there's a BBB problem. Regards, Buster So why isn't Cunningham testing for 24.3.1 w/ her study? I'm trying to make sense of all of this. My daughter's CaM KinaseII was in the SC range, but antilysoganglioside was not elevated. The only other elevation she had was the anti D2...does that mean she's convalescent? And I keep wondering if the blood levels correlate to brain levels? This is so confusing! Hi T.Mom, On the evidence that 24.3.1 falls at same rate as other two antibodies. There are essentially three elements: Swedo showed that system exacerbations tracked ASO titers for those PANDAS kids that had ASO response Kirvan showed that CaM Kinase II activation was substantially reduced in convalescent serum (see fig 3a in http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf) finally, Kirvan showed that antibody 24.3.1 activated Cam Kinase II (see figure 4a in http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf) What's interesting about fig 3a in the JNI paper is that 25% of the kids did not have a substantial change in their CaM Kinase II -- to me this indicates that perhaps their blood brain barrier closed rather than the antibody going away -- however, that's just conjecture. Okay, so what is CaM Kinase II, well, that's a tough topic. Let's see if a short answer works: Upon activation, CaM Kinase II turns on glutamate receptors on synapses. This changes the electrical property of the synapse. So if CaM Kinase II is happening incorrectly, it interferes with how the synapse works -- sort of like interference on a radio. So, if 24.3.1 causes CaM Kinase II activation, then if it crosses the blood-brain barrier, it could be causing incorrect signalling in the region of the brain sensitive to lysogangliosides and glutomate signalling (namely the basal ganglia). I realize that is 3 if's in a row, but that's about as far as the research has gotten. Hope that helps -- I can point you to papers if you really want details, Regards, Buster ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
peglem Posted August 16, 2009 Report Posted August 16, 2009 She just emphacized that the D2 was rather high, only 4 of the positives were that high=16000 at 120mins. Sorry for sidetracking the thread...I don't know how to move the post. We probably should have pulled this out to its own thread, ... I agree with you that your anti-lysogangliosides are pretty close to the negative controls. There are a couple of possibilities: a ) azithromycin is having an effect on the results -- there are papers that indicate macrolides affect the distribution of the components of CaM Kinase II b ) there's some other element driving elevated CaM Kinase II Did Cunningham offer any more details? Certainly unclear to me how to read those results. Regards, Buster I just had another look at her results. The anti-lysoganglioside is higher than the negative control #, (at 120mins.=160, the neg. control # is 80). Same thing with the anti-tubulin, at 120mins.=500, whereas neg. control is 250). I don't think my daughter has had a real exacerbation in over a year(since starting prophylactic zith), but her baseline is not so great, so its hard to say. So, does that mean she does show some elevation?Actually Cunningham is testing for 24.3.1 but only under the general category of anti-lysogangliosides (i.e., she's looking at competitive inhibition but is using the whole serum -- she's not isolating the antibody first). This is likely a cost issue. I'd imagine isolating the antibody would be quite expensive. The presumption is that the anti-lysogangliosides found in competitive inhibition are the 24.3.1, 31.1.1 and 37.2.1. Of these 24.3.1 is the only one that seems to really drive CaM Kinase II. So I suppose your question is "if the anti-lysogangliosides are low, why is her CaM Kinase II high?" Frankly, I'm not sure. CaM Kinase II can stay active for a while, but it is surprising that it's remaining high. I would have expected the anti-lysogangliosides to be elevated if the CaM Kinase II is activated. I guess that's the whole purpose of the current study. It may mean there is another cause. In terms of blood level and brain level, it looks like this is only correlated during an exacerbation. The nature paper reports CSF and Serum levels and these correlate in exacerbations. Hence the thought that there's a BBB problem. Regards, Buster So why isn't Cunningham testing for 24.3.1 w/ her study? I'm trying to make sense of all of this. My daughter's CaM KinaseII was in the SC range, but antilysoganglioside was not elevated. The only other elevation she had was the anti D2...does that mean she's convalescent? And I keep wondering if the blood levels correlate to brain levels? This is so confusing! Hi T.Mom, On the evidence that 24.3.1 falls at same rate as other two antibodies. There are essentially three elements: Swedo showed that system exacerbations tracked ASO titers for those PANDAS kids that had ASO response Kirvan showed that CaM Kinase II activation was substantially reduced in convalescent serum (see fig 3a in http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf) finally, Kirvan showed that antibody 24.3.1 activated Cam Kinase II (see figure 4a in http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf) What's interesting about fig 3a in the JNI paper is that 25% of the kids did not have a substantial change in their CaM Kinase II -- to me this indicates that perhaps their blood brain barrier closed rather than the antibody going away -- however, that's just conjecture. Okay, so what is CaM Kinase II, well, that's a tough topic. Let's see if a short answer works: Upon activation, CaM Kinase II turns on glutamate receptors on synapses. This changes the electrical property of the synapse. So if CaM Kinase II is happening incorrectly, it interferes with how the synapse works -- sort of like interference on a radio. So, if 24.3.1 causes CaM Kinase II activation, then if it crosses the blood-brain barrier, it could be causing incorrect signalling in the region of the brain sensitive to lysogangliosides and glutomate signalling (namely the basal ganglia). I realize that is 3 if's in a row, but that's about as far as the research has gotten. Hope that helps -- I can point you to papers if you really want details, Regards, Buster ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
Chemar Posted August 16, 2009 Report Posted August 16, 2009 I split this off into it's own thread at Buster's request
peglem Posted August 16, 2009 Report Posted August 16, 2009 I couldn't see anything but the initial post until I hit reply, so I copied it here. Cunningham did not offer any more details. I wonder if one of her other medications could have affected the results? What else could elevate Cam Kinase II ? QUOTE(Buster @ Aug 15 2009, 11:21 PM) *We probably should have pulled this out to its own thread, ... I agree with you that your anti-lysogangliosides are pretty close to the negative controls. There are a couple of possibilities: a ) azithromycin is having an effect on the results -- there are papers that indicate macrolides affect the distribution of the components of CaM Kinase II b ) there's some other element driving elevated CaM Kinase II Did Cunningham offer any more details? Certainly unclear to me how to read those results. Regards, Buster QUOTE(peglem @ Aug 15 2009, 10:57 PM) * I just had another look at her results. The anti-lysoganglioside is higher than the negative control #, (at 120mins.=160, the neg. control # is 80). Same thing with the anti-tubulin, at 120mins.=500, whereas neg. control is 250). I don't think my daughter has had a real exacerbation in over a year(since starting prophylactic zith), but her baseline is not so great, so its hard to say. So, does that mean she does show some elevation? QUOTE(Buster @ Aug 15 2009, 10:23 PM) * Actually Cunningham is testing for 24.3.1 but only under the general category of anti-lysogangliosides (i.e., she's looking at competitive inhibition but is using the whole serum -- she's not isolating the antibody first). This is likely a cost issue. I'd imagine isolating the antibody would be quite expensive. The presumption is that the anti-lysogangliosides found in competitive inhibition are the 24.3.1, 31.1.1 and 37.2.1. Of these 24.3.1 is the only one that seems to really drive CaM Kinase II. So I suppose your question is "if the anti-lysogangliosides are low, why is her CaM Kinase II high?" Frankly, I'm not sure. CaM Kinase II can stay active for a while, but it is surprising that it's remaining high. I would have expected the anti-lysogangliosides to be elevated if the CaM Kinase II is activated. I guess that's the whole purpose of the current study. It may mean there is another cause. In terms of blood level and brain level, it looks like this is only correlated during an exacerbation. The nature paper reports CSF and Serum levels and these correlate in exacerbations. Hence the thought that there's a BBB problem. Regards, Buster QUOTE(peglem @ Aug 15 2009, 08:53 PM) * So why isn't Cunningham testing for 24.3.1 w/ her study? I'm trying to make sense of all of this. My daughter's CaM KinaseII was in the SC range, but antilysoganglioside was not elevated. The only other elevation she had was the anti D2...does that mean she's convalescent? And I keep wondering if the blood levels correlate to brain levels? This is so confusing! QUOTE(Buster @ Aug 15 2009, 06:54 PM) * Hi T.Mom, On the evidence that 24.3.1 falls at same rate as other two antibodies. There are essentially three elements: * Swedo showed that system exacerbations tracked ASO titers for those PANDAS kids that had ASO response * Kirvan showed that CaM Kinase II activation was substantially reduced in convalescent serum (see fig 3a in http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf) * finally, Kirvan showed that antibody 24.3.1 activated Cam Kinase II (see figure 4a in http://www.pandasnetwork.org/Cunningham.NMpaper[1].pdf) What's interesting about fig 3a in the JNI paper is that 25% of the kids did not have a substantial change in their CaM Kinase II -- to me this indicates that perhaps their blood brain barrier closed rather than the antibody going away -- however, that's just conjecture. Okay, so what is CaM Kinase II, well, that's a tough topic. Let's see if a short answer works: Upon activation, CaM Kinase II turns on glutamate receptors on synapses. This changes the electrical property of the synapse. So if CaM Kinase II is happening incorrectly, it interferes with how the synapse works -- sort of like interference on a radio. So, if 24.3.1 causes CaM Kinase II activation, then if it crosses the blood-brain barrier, it could be causing incorrect signalling in the region of the brain sensitive to lysogangliosides and glutomate signalling (namely the basal ganglia). I realize that is 3 if's in a row, but that's about as far as the research has gotten. Hope that helps -- I can point you to papers if you really want details, Regards, Buster QUOTE(T.Mom @ Aug 15 2009, 04:06 PM) * ..." CaM Kinase II stays activated even with falling 24.3.1. There is apparently some hysterisis for some kids. There is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids. Perhaps for kids who show a rise in ASO, the fall is also a good indicator of T-cell regulation/suppression. There is mounting anecdotal evidence that colonized strep (rather than infection) is sufficient to trigger antibody response in PANDAS kids. So it could be that colonization is sufficient to cause a rise of 24.3.1 -- or that some kids just don't have rising ASO/Anti-DNAseB during infection (Kurlan indicates 36% of kids don't have a rise of ASO and Anti-DNAse B ) ....Buster" Buster thank you for the insight-- Do you have any info. on just what is Cam Kinase II? I am struggling with understanding what it is, and what, if anything else it may represent? And when you say that "there is good evidence that 24.3.1 falls at the same rate as the other two antibodies in 75% of kids" -- which antibodies are you referring to? Thank you again for this information- TMom
Phasmid Posted June 23, 2010 Report Posted June 23, 2010 I wanted to bump this up since it is very useful in general and questions repeatedly come up regarding the significance of these.
justinekno Posted June 23, 2010 Report Posted June 23, 2010 Good idea. I don't think I've read it since we've had our Cunningham test results. Thanks. I wanted to bump this up since it is very useful in general and questions repeatedly come up regarding the significance of these.
kimballot Posted June 24, 2010 Report Posted June 24, 2010 This is a very interesting thread - originially posted before my time on the forum. I want to see if I have this straight... when antibody 24.3.1 crosses the blood-brain barrier it activates cam Kinase (at least it does in PANDAS kids). Now... what makes the body produce 24.3.1. What is it's original purpose - is it originally designed to fight strep or is it designed to fight strep and other types of infections (that would make PITANDS more understandable). Also - anyone thinking of changing the name to PANDA24.3.1?? (Just kidding) Any further explanation would be appreciated. Thanks!
wornoutmom Posted June 24, 2010 Report Posted June 24, 2010 Just thought I'd mention that all our auto-antibody results were in normal range, with a Cam score of 167. Dr Cunningham noted that they do not understand yet why the two tests do not always match. Has this happened to anyone else?
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