Support for molecular mimicrytheorie The idea that molecular mimicry is the basis for the formation of autoimmune diseases, is a brilliant theoretical explanation. Due to lack of supporting research lost this theory, however, increasing credibility. Found by a research group in Leiden Cytomegalovirus
relationship between diabetes mellitus and converts the molecular mimicry all the way back on the card.
How it is that the immune system attacks at an autoimmune disorder body's own cells, is not yet clear. It seemed that there had to be sought in the direction of molecular mimicry. Since pathogenic organisms, for example, comprise peptides that correspond to structures on human cells, an auto-immune response occurs. A very beautiful theory.
Although repeatedly been shown to be pathogenic organisms and human cells have similar structures (see box), further evidence of the molecular mimicrytheorie is thin. In a review article in the New England Journal of Medicine and a half years ago set the immunologists Lori Albert and Robert Inman even that theory for any human autoimmune disorder opgaat.1 Seemed to this conclusion at that time not entirely justified, a recent discovery Leiden researchers from the mimicrytheorie even strengthened considerably.
Crossword
A loss in the article in the NEJM that is not called the disease of Guillain-Barré syndrome. These neurological autoimmune disease namely knows the strongest evidence to suggest that molecular mimicry plays a role in this neurological disorder. Structures on the lipopolysaccharide from Campylobacter jejuni correspond to gangliosides in the plasma membranes of the motoneurons. Also, there is a clear relationship between an epidemiological Campylobacter Infection and Guillain-Barré syndrome.
Moreover, there are known cases in which patients develop neurological symptoms after a Campylobacter infection that are very similar to the symptoms of patients with Guillain-Barré syndrome, but in which not the cranial nerves are affected. Finally, there is still a number of in-vivo and in-vitro studies supporting the hypothesis. To quote the American philosopher Susan Haack science: scientific crossword about the cause of Guillain-Barré syndrome has so far completed, that molecular mimicry outgrows the stage of a theory.
Why the NEJM article ignores Guillain-Barré syndrome is not clear by asking one of the two authors. Whether in a review article about a disease mechanism the sample with the strongest evidence in favor of the mimicrytheorie may be missing, dodging Robert Inman consistent. "The peer reviewers asked us to shorten the article by reducing the number of illnesses", he says in an email. "Besides, we (Albert and Inman, ed.), Rheumatologists, and we have therefore focused on our joint disorders." Asked whether Guillain-Barré syndrome have occurred in a previous version of the review article, Inman does not answer. His second argument is simply not true. The article does elaborate on the evidence of molecular mimicry in diabetes, multiple sclerosis and other neurological disorders. At least there is in placing the review article there is a strange acceptance policy. Control is also, however, not be ruled out; Also scientific journals are indeed sensitive fashion.
substantiation
Also biochemist dr. BJ Apple Milk surprising to see that the NEJM article says nothing about Guillain-Barré syndrome. The biochemist, attached to the Department of Medical Microbiology at the Free University of Amsterdam, believes that this condition satisfies all the conditions which Albert and Inman appoint a foundation of molecular mimicrytheorie. "Not that I'm an expert on Guillain-Barré" hurry Appelmelk to say. "But the procedures for the substantiation of the theory I know it very well."
That Apple Milk conditions knows so well is because of this scientist less pleasant experience. In 1996 he published an article on molecular mimicry in autoimmune phenomena in the stomach by infection with Helicobacter pylori.2 The immune system would be mistaken because structures for H. pylori are the same blood types that occur on mucosal epithelial cells. Antibodies directed against H. pylori would cause damage to the stomach lining, with gastritis and pernicious anemia as a result.
"I was convinced that mimicry was the cause of the infection by H. pylori induced autoantibodies," said Apple Milk. "But it turned out quite different to sit together. There is, however of an auto-immune response as a result of an infection with H. pylori, but plays no role of molecular mimicry. " A year after the article on mimicry Appelmelk published the data earlier findings tegenspraken.3 4
"A condition for molecular mimicry is, of course, that there is question of cross-reactive T-cells or antibodies. However, it has become clear in the course of the time that T-cells themselves behave promiscuous. Screening for example thousand peptides proliferation assay in a T-cell cross-reactivity occurs much more than you would expect based on the amino acid sequence. Now how many genes there are some known and how much protein coding genes and knowing that there are a lot of viruses, it is not surprising that cross-reactivity occurs. Purely on the basis of probability. But that need not have biological significance. Without further clinical evidence cross-reactivity means no more than a good start. "
In the 'further proof' of the examination Appelmelk ran spoke at a given time. In spite of the identical epitopes showed that it stomach wall cells, but does not recognize the bacterium the serum of patients with H. pylori infection. This was clear to the Amsterdam research that there is no mimicry.
"The article by Albert and Inman describes very well what requirements must be met, wants a disease by molecular mimicry come about," Apple Milk continues. "The gist of their piece is that it has been demonstrated in animal models, but that the molecular mimicrytheorie is not impervious to humans. The literature on molecular mimicry has been so extensive, however, that there are quite a review article can be written that the theory does support. It's just what selection you applied. "
The review article in the NEJM be very one-sided, perhaps related to the figurative mimicrymoeheid that followed the hype surrounding this topic. "At one time the cause was any autoimmune disease sought in mimicry," explains researcher Bart diabetes Call of the department Immuno Haematology and Blood Transfusion of the Leiden University Medical Center Post. "Disappointing research have faith in molecular mimicry then greatly affected. That was true for myself. After another publication about the alleged relationship between infection with Coxsackie virus and diabetes mellitus I had had it with the theory. "
Meanwhile, call back all the way. More or less by chance came across his research on the relationship between diabetes and cytomegalovirus. T-cells from a patient with stiff man syndrome (Neuromyotonia), a neurological disorder that is often accompanied by diabetes mellitus type 1, bleaching directed against both human GAD65 protein as opposed to a piece of a protein of the cytomegalovirus.5 This patient appeared before they recorded it got stiff man syndrome, with severe CMV infection. " The cross-reactivity can lead to two completely different syndromes caused by different reactions of the immune system, "explains Cry. In diabetes, there is a T-cell reaction, in the formation of an antibody Neuromyotonia, so that nerves are affected. This leads to sudden and prolonged contractions of the skeletal muscles.
Literature study strengthened the evidence for the mimicrytheorie. An epidemiological link had already been proven. In addition, the virus is specifically able to infect the insulin-producing beta cells, nerve cells and immune cells. Furthermore, in animal research is clear that infection with CMV in mice immediately leads to destruction of the islets of Langerhans.
Further evidence must come from research to show whether the cross-reaction occurs in more diabetic patients. "We'll figure out in the short term," says Call. More support, for example, come from a project of the National Health Service. In that study defines minutely from birth when children get the infection. However, the epidemiological study will only give answers on a minimum of fifteen years. '
Although it is evident that there are other mechanisms that lead to auto-immune diseases, and it is established that not all diabetes is a result of infection with CMV, doubts call there is absolutely not indicate that there is, in any case, in the specific patient of molecular mimicry . "I dare to put it to my head on the block." Several scientific journals have had considerably more doubt. Call before the article in the prestigious Proceedings of the National Acadamie of Sciences (PNAS) published, he received twice a negative response after submitting the article. "Nature Medicine complimented us with research, but did not dare to publish them. Lancet we received similar comments. She thought it was too good to be true. The resistance to the mimicrytheorie is apparently great. "
Vaccination
Mimicrytheorie that is not embraced by everyone, is not strange. As mentioned, the evidence long remained very sketchy. Also, it is still largely unclear why there are so relatively few patients with auto-immune diseases, while infection infinitely often occurs. Moreover, has never been demonstrated that there is a relationship between auto-immune diseases and vaccination, while nevertheless the potential hereby homologous epitopes are administered to human beings. It is also clear that an infection by different mechanisms may lead to auto-immunity. Auto-immune T-cells that are not escaped in the thymus to selection, for example, be able to proliferate by an infection. And even if there is any mimicry, this does not have to be the cause of the auto-immunity. It may, according to immunologists also a result of it. The gay homology can be caused by infectiegemedieerde epitoopveranderingen, as can be seen in the NEJM article of Albert and Inman.
Without substantive examination of the publication of Call - Inman knows the investigation is not - keep the door well ajar for molecular mimicry. "PNAS is a good magazine. If this research meets the criteria for pathogenesis as we have noted in the review article, I'm convinced. " As befits a good scientist, Inman apparently realizes that there are many roads that lead to Rome. <<
relationship between diabetes mellitus and converts the molecular mimicry all the way back on the card.
How it is that the immune system attacks at an autoimmune disorder body's own cells, is not yet clear. It seemed that there had to be sought in the direction of molecular mimicry. Since pathogenic organisms, for example, comprise peptides that correspond to structures on human cells, an auto-immune response occurs. A very beautiful theory.
Although repeatedly been shown to be pathogenic organisms and human cells have similar structures (see box), further evidence of the molecular mimicrytheorie is thin. In a review article in the New England Journal of Medicine and a half years ago set the immunologists Lori Albert and Robert Inman even that theory for any human autoimmune disorder opgaat.1 Seemed to this conclusion at that time not entirely justified, a recent discovery Leiden researchers from the mimicrytheorie even strengthened considerably.
Crossword
A loss in the article in the NEJM that is not called the disease of Guillain-Barré syndrome. These neurological autoimmune disease namely knows the strongest evidence to suggest that molecular mimicry plays a role in this neurological disorder. Structures on the lipopolysaccharide from Campylobacter jejuni correspond to gangliosides in the plasma membranes of the motoneurons. Also, there is a clear relationship between an epidemiological Campylobacter Infection and Guillain-Barré syndrome.
Moreover, there are known cases in which patients develop neurological symptoms after a Campylobacter infection that are very similar to the symptoms of patients with Guillain-Barré syndrome, but in which not the cranial nerves are affected. Finally, there is still a number of in-vivo and in-vitro studies supporting the hypothesis. To quote the American philosopher Susan Haack science: scientific crossword about the cause of Guillain-Barré syndrome has so far completed, that molecular mimicry outgrows the stage of a theory.
Why the NEJM article ignores Guillain-Barré syndrome is not clear by asking one of the two authors. Whether in a review article about a disease mechanism the sample with the strongest evidence in favor of the mimicrytheorie may be missing, dodging Robert Inman consistent. "The peer reviewers asked us to shorten the article by reducing the number of illnesses", he says in an email. "Besides, we (Albert and Inman, ed.), Rheumatologists, and we have therefore focused on our joint disorders." Asked whether Guillain-Barré syndrome have occurred in a previous version of the review article, Inman does not answer. His second argument is simply not true. The article does elaborate on the evidence of molecular mimicry in diabetes, multiple sclerosis and other neurological disorders. At least there is in placing the review article there is a strange acceptance policy. Control is also, however, not be ruled out; Also scientific journals are indeed sensitive fashion.
substantiation
Also biochemist dr. BJ Apple Milk surprising to see that the NEJM article says nothing about Guillain-Barré syndrome. The biochemist, attached to the Department of Medical Microbiology at the Free University of Amsterdam, believes that this condition satisfies all the conditions which Albert and Inman appoint a foundation of molecular mimicrytheorie. "Not that I'm an expert on Guillain-Barré" hurry Appelmelk to say. "But the procedures for the substantiation of the theory I know it very well."
That Apple Milk conditions knows so well is because of this scientist less pleasant experience. In 1996 he published an article on molecular mimicry in autoimmune phenomena in the stomach by infection with Helicobacter pylori.2 The immune system would be mistaken because structures for H. pylori are the same blood types that occur on mucosal epithelial cells. Antibodies directed against H. pylori would cause damage to the stomach lining, with gastritis and pernicious anemia as a result.
"I was convinced that mimicry was the cause of the infection by H. pylori induced autoantibodies," said Apple Milk. "But it turned out quite different to sit together. There is, however of an auto-immune response as a result of an infection with H. pylori, but plays no role of molecular mimicry. " A year after the article on mimicry Appelmelk published the data earlier findings tegenspraken.3 4
"A condition for molecular mimicry is, of course, that there is question of cross-reactive T-cells or antibodies. However, it has become clear in the course of the time that T-cells themselves behave promiscuous. Screening for example thousand peptides proliferation assay in a T-cell cross-reactivity occurs much more than you would expect based on the amino acid sequence. Now how many genes there are some known and how much protein coding genes and knowing that there are a lot of viruses, it is not surprising that cross-reactivity occurs. Purely on the basis of probability. But that need not have biological significance. Without further clinical evidence cross-reactivity means no more than a good start. "
In the 'further proof' of the examination Appelmelk ran spoke at a given time. In spite of the identical epitopes showed that it stomach wall cells, but does not recognize the bacterium the serum of patients with H. pylori infection. This was clear to the Amsterdam research that there is no mimicry.
"The article by Albert and Inman describes very well what requirements must be met, wants a disease by molecular mimicry come about," Apple Milk continues. "The gist of their piece is that it has been demonstrated in animal models, but that the molecular mimicrytheorie is not impervious to humans. The literature on molecular mimicry has been so extensive, however, that there are quite a review article can be written that the theory does support. It's just what selection you applied. "
The review article in the NEJM be very one-sided, perhaps related to the figurative mimicrymoeheid that followed the hype surrounding this topic. "At one time the cause was any autoimmune disease sought in mimicry," explains researcher Bart diabetes Call of the department Immuno Haematology and Blood Transfusion of the Leiden University Medical Center Post. "Disappointing research have faith in molecular mimicry then greatly affected. That was true for myself. After another publication about the alleged relationship between infection with Coxsackie virus and diabetes mellitus I had had it with the theory. "
Meanwhile, call back all the way. More or less by chance came across his research on the relationship between diabetes and cytomegalovirus. T-cells from a patient with stiff man syndrome (Neuromyotonia), a neurological disorder that is often accompanied by diabetes mellitus type 1, bleaching directed against both human GAD65 protein as opposed to a piece of a protein of the cytomegalovirus.5 This patient appeared before they recorded it got stiff man syndrome, with severe CMV infection. " The cross-reactivity can lead to two completely different syndromes caused by different reactions of the immune system, "explains Cry. In diabetes, there is a T-cell reaction, in the formation of an antibody Neuromyotonia, so that nerves are affected. This leads to sudden and prolonged contractions of the skeletal muscles.
Literature study strengthened the evidence for the mimicrytheorie. An epidemiological link had already been proven. In addition, the virus is specifically able to infect the insulin-producing beta cells, nerve cells and immune cells. Furthermore, in animal research is clear that infection with CMV in mice immediately leads to destruction of the islets of Langerhans.
Further evidence must come from research to show whether the cross-reaction occurs in more diabetic patients. "We'll figure out in the short term," says Call. More support, for example, come from a project of the National Health Service. In that study defines minutely from birth when children get the infection. However, the epidemiological study will only give answers on a minimum of fifteen years. '
Although it is evident that there are other mechanisms that lead to auto-immune diseases, and it is established that not all diabetes is a result of infection with CMV, doubts call there is absolutely not indicate that there is, in any case, in the specific patient of molecular mimicry . "I dare to put it to my head on the block." Several scientific journals have had considerably more doubt. Call before the article in the prestigious Proceedings of the National Acadamie of Sciences (PNAS) published, he received twice a negative response after submitting the article. "Nature Medicine complimented us with research, but did not dare to publish them. Lancet we received similar comments. She thought it was too good to be true. The resistance to the mimicrytheorie is apparently great. "
Vaccination
Mimicrytheorie that is not embraced by everyone, is not strange. As mentioned, the evidence long remained very sketchy. Also, it is still largely unclear why there are so relatively few patients with auto-immune diseases, while infection infinitely often occurs. Moreover, has never been demonstrated that there is a relationship between auto-immune diseases and vaccination, while nevertheless the potential hereby homologous epitopes are administered to human beings. It is also clear that an infection by different mechanisms may lead to auto-immunity. Auto-immune T-cells that are not escaped in the thymus to selection, for example, be able to proliferate by an infection. And even if there is any mimicry, this does not have to be the cause of the auto-immunity. It may, according to immunologists also a result of it. The gay homology can be caused by infectiegemedieerde epitoopveranderingen, as can be seen in the NEJM article of Albert and Inman.
Without substantive examination of the publication of Call - Inman knows the investigation is not - keep the door well ajar for molecular mimicry. "PNAS is a good magazine. If this research meets the criteria for pathogenesis as we have noted in the review article, I'm convinced. " As befits a good scientist, Inman apparently realizes that there are many roads that lead to Rome. <<
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