How does multiple sclerosis differ from other autoimmune diseases

Why drugs for autoimmune diseases do not help with multiple sclerosis

Kirill Stasevich, Compulenta

Researchers have found a mutation that distinguishes multiple sclerosis from other autoimmune disorders and makes it resistant to the therapy common for such ailments.

Multiple sclerosis: immune cells of the nervous system (yellow)
they attack oligodendrocytes, the "support service" of neurons.
(Photo by Dr John Zajicek.)

When people talk about the genetic causes of diseases such as diabetes, cancer or multiple sclerosis, the first thing you can hear is that there is no single culpable gene here. In most cases, the disease occurs due to a variety of genetic problems. Individually, they do not greatly increase the likelihood of an ailment, but in total, the percentage runs up serious. Therefore, when looking for mutations that cause cancer or multiple sclerosis, the work goes on the scale of the genome, the complete DNA sequences of different people are analyzed and compared.

And although there really is no one genetic root cause for such diseases, it is possible to determine what each individual mutation is responsible for. And it is even necessary: because sometimes it gives the clinical picture of the disease something that distinguishes it from others. This is exactly the case with multiple sclerosis. This is an autoimmune disease, but when they try to treat it with the help of standard medications in such cases, it only gets worse.

Autoimmune disorders are known to occur due to malfunctioning TNF protein, or tumor necrosis factor. This protein has a partner-a receptor that sits on the surface of cells and catches TNF molecules floating by. This pair is responsible, among other things, for the detection and destruction of cancer cells by the immune system, but if something goes wrong in molecular interactions, a harmful autoimmune attack is triggered.

The paradox is that drugs that block the TNF receptor and usually help with autoimmune disorders are useless at best in multiple sclerosis. Researchers from Oxford (Great Britain) tried to find out what was the matter, for which they thoroughly analyzed the genomic maps of those suffering from multiple sclerosis. It turned out that there is one mutation in the TNF gene that increases the likelihood of getting multiple sclerosis by 12%. The mutation is reduced to two nucleotide substitutions in the protein gene (two adenine "letters" are changed to two guanine), as a result of which a shortened version of the TNF receptor is synthesized.

Usually the receptor sits in the membrane, but in a shortened form it leaves it, moving away into the intercellular space. And those drugs that prevent TNF from connecting to its receptor and that help so well, for example, with autoimmune rheumatoid arthritis, do not work with multiple sclerosis. And not only do they not work, but they even increase the disease. There are, of course, many mysteries here: for example, in experiments on mice, the same drugs worked very well against multiple sclerosis. Obviously, the human variant of the disease has some specifics.

Further: blocking the interaction of TNF and its receptor obviously plays into the hands of multiple sclerosis, but why this is so, why a free–floating TNF receptor contributes to the disease - all this needs to be studied and studied. However, even now, doctors could take the data obtained into service and use genetic methods in advance to select a treatment for the patient that at least did not harm him.

The results of the study (Gregory et al., TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis) are published in the journal Nature.

Prepared based on materials from Oxford University: Gene link to MS explains drug side effects.

Portal "Eternal youth" http://vechnayamolodost.ru11.07.2012