Study on identical twins shows early form of Multiple Sclerosis has special pattern
They are about as “easy” to find as the proverbial needle in the haystack: identical twins, one of whom has Multiple Sclerosis (MS) and one doesn’t. Neuroimmunologists in Munich have – to stay with the image – put together an entire set of needles, and their colleagues in Münster have analysed the blood samples taken from these twins. Now, on the basis of 43 such sets of twins, they looked to see whether there are certain indicators in the immune system which account for MS – in other words, something like a “signature” of the diseases. The study produced a surprising result. The results are published in the journal PNAS.
They are about as “easy” to find as the proverbial needle in the haystack: identical twins, one of whom has Multiple Sclerosis (MS) and one doesn’t. Neuroimmunologists in Munich have – to stay with the image – put together an entire set of needles, and their colleagues in Münster have analysed the blood samples taken from these twins. Now, on the basis of 43 such sets of twins, they looked to see whether there are certain indicators in the immune system which account for MS – in other words, something like a “signature” of the diseases. The study produced a surprising result.
The team found that there is hardly any difference in the composition of the individual cell types in the blood. This would not be surprising in healthy sets of twins, given that they share the same genes and environmental influences. “But MS also has hardly any influence on signatures in the blood,” comments Claudia Janoschka, a PhD student in the team headed by Prof. Luisa Klotz, a neuroimmunologist and consultant in Münster. Only around one percent of the differences between twins where one is healthy and the other has the illness can in fact be explained by the MS. In view of the far-reaching damage which this insidious illness causes to the nervous system – and, as a consequence, to movement, language and thinking ability – this is remarkable. By way of comparison: the factor “age” alone is responsible for four percent of the differences in the composition of the immune cell network.
But there was one important feature which the researchers did discover: not all of those twins who appeared to be the healthy one were in fact free of any indications of MS. Some of them showed latent indications of this disease of the central nervous system – even in cases where the disease had not broken out at all. “These people, with MS in a possible preliminary stage, should actually be more similar, as regards the composition of their immune cells, to patients in whom the disease has been diagnosed than to those who have no indications of the disease,” says Janoschka. Indeed, the researchers – working within Collaborative Research Centre (CRC) TR128, “Multiple Sclerosis”, funded by the German Research Foundation (DFG) – did find one thing in common: there was a clear match especially in CD4-positive effector T cells which are involved in the inflammation process. “Presumably, therefore, these play an important role in the early stages of MS,” concludes Janoschka, one of the two lead authors of the study, which has now been published in the highly respected journal PNAS. “These exciting results are another example of how research involving twins can make very valuable contributions to understanding MS,” comments co-lead author Dr. Lisa Ann Gerdes from the Institute of Clinical Neuroimmunology at Munich University Hospital (LMU).
The fruitful collaboration between the researchers in Munich and Münster was made possible by setting up a clinical translation platform for the systematic and standardised study of patient material in the “Multiple Sclerosis” CRC. “The technical possibilities now established here enable us to examine challenging questions by directly using patient samples,” explains Prof. Klotz, who heads the collaborative project.
These findings are equally important for the development of new forms of treatment. Multiple Sclerosis has to be treated as fast as possible – if not, it leaves behind irreversible damage. In other words, medicines which inhibit CD4-positive effector T cells could be used as a strategy in the prevention of MS in risk candidates.
Background: the MS twin cohort
The national MS twin cohort currently comprises 85 sets of identical twins, where one twin in each pair has MS and the other is, at least “clinically”, healthy. As each set of twins has the same genes, this constellation opens up unique opportunities for research into the role of non-genetic influences on the development of MS – e.g. the influence of intestinal flora (microbiota) or the role played by epigenetic changes. The national MS twin cohort at Munich University Hospital is headed by Dr. Lisa Ann Gerdes and Prof. Reinhard Hohlfeld. It is funded by, among others, the German Research Foundation (SyNergy Cluster of Excellence), the non-profit making Hertie Foundation, and the German Multiple Sclerosis Society (both the national association and the Bavarian association)
Medizinische Fakultät der Westfälischen Wilhelms-Universität Münster
Klinik für Neurologie mit Institut für Translationale Neurologie
PD Dr. Lisa Ann Gerdes
Institut für Klinische Neuroimmunologie
Gerdes LA, Janoschka C, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A, Ertl-Wagner B, Barkhof F, Meuth SG, Kümpfel T, Wiendl H, Hohlfeld R, Klotz L. Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proc Natl Acad Sci U S A. Doi: 10.1073/pnas.2003339117