"Immunosenescence..." here because I am so being a CPn apologist and did not wan to be hijacking the general thread. PLEASE READ THE EARLIER POSTS THERE FIRST..marie
You are thinking long about this subject. this is what's fun about this board where we can talk and think all we want about this most important subject. We have to base treatment decisions on models that have resulted in limited success leaving many of us frustrated about wht to do in our personal cases NOW because we can't wait for research to catch up. After 15 years of MS and being told in the beginning that in 5 years there would be a cure, I have come to the conclusion that the mainstream researchers have made a serious error in the basic model.
This paper (I've read the whole citation) outlines what is wrong with MS research http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum If you are interested in the differences between EAE and MS in terms of cellular responses ie which interleukins are in EAE which MS etc, this is the bulk of this paper. The case is EXTREMELY well made that EAE is utterly different. the abstract is really understated.
After extensive reading, I believe the CPn possibility. This is my bias. Now on the the interesting questions raised
If you put apoptosis and chlamydia pneumonia in the search box you'll get lots of references. I'm not going ot pick just one. I cited in the earlier thread a paper that outlines decreased apoptosis in CMV, a known viral strategy for preserving the home of the germ Did you know CPn was at first thought to be a virus? This was because it takes over the cell and uses it to relplicate itself as viruses do. It was only later that it was seen that this bacteria has DNA not just RNA, making it a bacteria because it has that much more genetic material. And that material allows it to do many things viruses cannot do, like change forms.
Now this next point reads like a drama novel. Margaret Hammerschlag MD(MH) whose paper you quoted was an outspoken critic of the CPn MS connection. The paper you chose as Mac says is too old to be relevant. Here's what was going on back then:
Vanderbilt university (VU)produced a paper in 99 that said that MS and CPn were related and that people treated with abx got better. At that time MH was considered expert on childhood STD's thus including chlamydia trachomatis, a bacteria that shares only about 10% of it's genes with CPn http://www.ncbi.nlm.nih.gov/entrez/quer ... t=Citation . This is very little similarity actually. She commented that the link between CPN and MS was intriguing to her so she obtained CFS samples from pwMS and controls to replicate the research. They cultured the CFS for CPn, using differet methods than those used at VU, and then of course as you show did not find any connection at all. In fact they seemingly found less in MS than in regular controls. (remember this her later work offers an explanation)
Sriram responded that her methods were inaccurate.
She responded let's do a blind test and well see who finds what. They did this and it is below:
This was found here:http://www.mult-sclerosis.org/news/Jan2001/InfectiousLinkstoMSQuestioned.html This paper is largely negative about CPn and all infectious causes. Please do not cut and paste chunks of this old paper and use it to "prove" MS and CPn have no link, I included the link here and everyone else can read it just like I have. It is someone's opinion based on available research at that time, not a study and has no relevance. I want to point out the obvious from the quote above howeverSriram responded by saying, "The fact that they can't find it in the brain is not surprising at all" because of difficulties his group had finding C. pneumoniae after injecting it into the brains of mice. "We know we put the bug there," he said. "But we're having difficulty finding out exactly what the conditions are to extract it from brain tissue. I don't know why."
To help settle the dispute, Sriram agreed to participate in a blinded study with three other teams. All received spinal fluid from patients with MS and controls, sent by Michael Kaufman, MD, of the MS Center of the Carolinas Medical Center in Charlotte, NC. The results, presented at the 2000 meeting of the American Neurology Association, further isolate the Vanderbilt team, who found C. pneumoniae DNA in 22 (73%) of 30 MS cases and in 5 (23%) of 22 controls. The other teams, at Johns Hopkins, the Centers for Disease Control and Prevention, and Umeå University, detected no traces of the organism.
Hammerschlag said the mass of evidence points to contamination or a lack of experience with delicate screening tests on the part of Sriram and his colleagues. "All of his work is being published in neurology journals, and they just kind of accept the methods. None of it would get published in microbiology journals," she said.
The VU team was given a blind (they did not know what samples were from which person) batch of CFS samples from MS and controls from an unbiased third party. They found CPn in high numbers in the MS people but not controls once the study was unblinded by the impartial person. And in MH's labs, three of them, they did not find any CPn. (It is this you quoted above). She was widely quoted in the press as saying that VU had contaminated their samples. She was interviewed by the MS society and various MS related media. always her interview was her dogmatically stating her point as if it were indisputable . Uh, wait a minute excuse me??? VU found high numbers of CPn in specifically the MS samples, and in numbers similar to their other work on MS and CPn and what happened was that they contaminated the samples??? How come the 22 control samples were not similarly "contaminated" since this was blind and they could not know which was which? This is an absurd conclusion which is simply unfounded by this unusual contest between labs. The better conclusion is that the VU lab has found a way to detect these subtle persistent infections in MS patients. (In fact in later work, VU and another lab in a similar blind study had similar rates of finding CPn in MS at both labs using different tests in blind split samples, again proving their effetiveness at detecting CPn. http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum )
The fact of the matter is that the stature of our expert here was in question. Supposedly we have the US top chlamydia expert and her labs can't find what VU can. She had to slam this work or look certainly less than expert because she could not find CPn and they did. She HAD to conclude they were fools of some kind or admit she was making a mistake Her peevish comment that microbiology journals would not publish this work, that neuro journals are somehow stupid about what they accept is belied by later acceptance of several papers by the VU team on their culturing techniques in other journals, including this one the clinical and diagnostic lab journal http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
Her opinion that the culturing techniques would not be acceptible to people inside the diagnositc world was flat wrong.
In fact MH has changed her tune about culturing CPn since then, though she has not revisited the MS issue nor has she revised her earlier statements. In this later paper she says that it is impossible to culture persistent infections and therefore we cannot evaluate the efficiency of antibiotic treatment in people because we can't tell who had persistent CPn and who not. From a scientific standpoint because we can't test and see this one is infected this one not, it makes it impossible to apply the scientific method. Mind you this does not mean that abx do not help the ones who are infected, but rather according to her that we can't evaluate it, because we are incapable of making the connection between seropositivy and abx response. http://www.ncbi.nlm.nih.gov/entrez/quer ... ed_docsums OK so here is what is fact based on this paper. Some people have persistent infection That's a fact. This infection is indetectible to the average lab (though VU seems ot be able to do it). That's a fact. Why is it such a stretch that this persistent infection might potentially be in the brain? Clearly, just because we can't culture it does not mean it's not there which is exactly what this paper says.
Ok now I am going to harken you back to the fact that in MH'S earlier lab contest they did not find ANY cpn in their samples. Her above work literally negates those findings because she says labs cannot detect persistent infection. It is intersting to interject again at this point that VU wand FUMCcan and do culture it in MS brains often.
If you enter PCR and chlamydia pneumoniae in pubmed you get pages of citations almost all of which show very inconsistant results in culturing CPn. In head to head PCR approaches, some find it and some don't. but alter the samples (known to be infected with CPn) and the most effective test changes so that no one can say this part of the gneome is the one to amplify in PCR for consistent results or that this test is the one performing best. I will post a thread on this interesting material soon in this forum because it is so key
http://www.ncbi.nlm.nih.gov/entrez/quer ... d=16136465
this list is of studies related to MS anc CPn. A quick scan of these papers, which is a list of papers related to MS and CPn, 4 find no association, 4 are inconclusive and 12 find an association in at least a subset. This is NOT a weak link, nor is it one lone researcher. It is many people all over the world that find it.
This is not proven of course but let's get real, neither is the theory that MS is autoimmune, and most of us have been treated with numerous immunosuppressives. Based on the theory it will help. Few of us can say our disease has been arrested by immunosuppression, and studies bear this out.
Just quickly to address the rest: Genetics; there is no reason at all genetics and CPn are not compatible. Rheumatic fever has a genetic component, but that doesn't mean that abx do not help, they do.
The age angle: The main problem you are having is that you coming back to the idea that if you have rising titres you must necessarily have an increasing MS incidence if it's related. It seems to you a direct cause and effect: get this germ get this illness. It is not like that at all. Fact: everyone is exposed, CPn's endemic IF it is the cause of MS it is a rare complication and it happens relatively early in life if it's going to. Since rheumatic fever is also a rare complication of an endemic germ we have evidence for this happening in the germ world already. In the case of RF, and probably MS if it is related to CPn, there is a genetic component. it is susceptible people who get this rare complication and again they get it early in life.
As for the infective angle, again: It's not "get this germ get this effect". No one is saying that. The faroe islands suggest an infective angle in spite of your assertion it' can't be infective because spouses do not get MS from their affected mates. I can't stress this enough: reactions are individual based on YOU. For goodness sake, if the bird flu gets here apparently in some strains half will die, in others 10%. If spouses catch it one may die . Will you say since the other did not it was a different germ? It is never a case of get this germ get this outcome. Never. Even polio affected people all they way from benign infection where they did not know they were ill (95%) to death (extremely rare). All we are talking about here if CPn plays a role in MS development is another kind of rare complication, but it's even more rare than most.
I think you are very logical in your assessment of what is happening, but I also think your "CPn can't be it" bias is coloring your ability to assess this possibility. A good example is snipping a piece out of a 2000 paper as if it is the last word on whether or not CPn is in MS brains or not. There have been numerous papers since then finding it by many researchers, and even the author of the snipped quote producing an expert opinion later stating that we are incapable of culturing persistent infection, which clearly says that her earlier paper which found "no chlamydia pneumoniae" is completely irrelevant. Furthermoe there has been vindication of the VU approach in that it was accepted in a diagnositic lab journal for publication.
The fact is that this subject is alive and well in the reseach community. people with vastly more education and understanding than you or I are weighing on on both sides of this issue. It is not proven, but nor is it disproven. It is not short sighted or naive to do treatment empirically nor are people missing something important.
I'm the last person to say everyone should do it. In the oft discussed here luccinetti research there are 4 types of MS lesions. In my opinion some of us have this issue, some probably do not. For ME PERSONALLY it is a good candidate because I have asthma and seronegative arthritis also. While the connection to MS is pretty well just beginning to look compelling, the connection to asthma is WELL established. It is not only possible for me personally but plausible. Perhaps the other lesions are impacted by hormones.