05 November 2008

Autoantibodies will help predict brain diseases

Garbage for removalAlla Astakhova, "Results" No. 45-2008

According to WHO, about 20 percent of the world's inhabitants suffer from hypertension. The consequences of this disease are strokes and chronic brain diseases called encephalopathies. In Russia in 2007 there were more than 400 thousand strokes, in Moscow and St. Petersburg recently it is the main cause of death. Encephalopathies are no less dangerous: according to experts, about 500 million people suffer from them on the planet. At the same time, you can not notice the first manifestations of the disease for a long time. There are different symptoms - someone has a headache, someone has tinnitus, someone has memory problems. They are often attributed to age, considered manifestations of fatigue. When the appropriate diagnosis is made, it turns out that the treatment is overdue. But it is known that almost half of the patients suffering from Alzheimer's disease have passed the stage of chronic encephalopathy. Clinicians in such cases just shrug their hands: of course, it would be good to be able to predict how hypertension will end for a particular patient, and to prevent serious consequences... However, it seems that a solution will be found soon - and a molecular test based on the analysis of the composition of autoimmune antibodies of the body, developed by scientists of the P.K. Anokhin Research Institute of Normal Physiology of the Russian Academy of Medical Sciences, will help in this.

About the benefits of garbage "The difficulty lies in the fact that there are practically no methods for assessing early brain disorders," says Vladimir Sherstnev, deputy director of the Institute, head of the Laboratory of Functional Neurochemistry.

 - It is very difficult to catch early changes in attention, memorization." The questionnaires and scales accepted in psychology are quite subjective. In addition, there are not enough relevant neuropsychologists in Russian clinics. Early pathological changes occurring in the brain are not recorded by magnetic resonance imaging. The processes go on at a very subtle level in the brain structures. Perhaps, only by identifying changes in the molecular composition of brain tissues, it would be possible to make a preliminary diagnosis. However, how to "disassemble into molecules" a living working brain?

Antibodies, special molecules produced by lymphocytes, came into the field of view of scientists. For a long time it was believed that antibodies appear in the body in response to foreign proteins penetrating into it and that this is how the immune system fights the factors attacking it. Each such molecule is able to bind to a certain fragment of the molecule of its "own" protein according to the "key - lock" principle. Antibodies act as "scavengers" in the body, sending proteins to the enzyme melting furnace of the body. However, later it turned out that the body produces antibodies not only to other people's proteins, but also to its own. Why is this necessary? For example, in order to fight the products of cellular decay. After all, hundreds of thousands of cells die in the human body every day. And autoantibodies-"scavengers" rake out a lot of proteins - from the liver, pancreas, brain…

But that's not all. There comes a time when autoantibodies have done their job. They also need to be disposed of. And for this, their own antibodies appear. "There are antibodies of several orders," says Vladimir Sherstnev. - The whole process looks like this. A first-order antibody is produced to a protein molecule, then a second-order antibody is produced on it, and so on. Now up to 14 orders of antibodies have been detected." It turns out that by the composition and number of antibodies in human blood, it is possible to judge the processes that occur with the "working machines" of the body - proteins. Scientists have found out that this way you can look into the most mysterious human organ, the brain. "We found out that early indicators of chronic encephalopathy can be autoantibodies to components of brain tissues, especially to those substances that are characteristic only of the nervous system," says Sherstnev. "These are proteins that are not present in other organs and are directly related to ensuring the functioning of the brain."

Killers and helpers Twenty-five years ago, when scientists started working on the problem, everything did not look so simple.

"We started our research with other brain diseases," says Marina Gruden, a leading researcher at the Laboratory of Functional Neurochemistry at the Research Institute of Normal Physiology. "Our first wards were patients with epilepsy and schizophrenia." At that time, psychiatrists treated such experiments at least cautiously, and often even called it quackery. It was believed that the brain is a barrier organ: no antibodies can simply penetrate it. Only in the 80s of the last century, scientists still found immune cells in it. "Our experiments have shown that the brain is permeable," says Gruden. - In our experiments, we labeled proteins with radioactive iodine, which were injected into the blood of laboratory rats. We then found about 25 percent of this iodine in the brain."

The first diagnostic task that scientists tried to solve using the new method was the problem posed by neonatologists. According to Marina Gruden, up to 50-60 percent of newborns suffer from brain disorders. The cause is both fetal hypoxia and viral diseases in the mother. After conducting an examination, we found quite a lot of maternal antibodies in infants, which acted as regulatory factors that did not allow the structures of the child's brain to develop normally at the fetal level. The research was carried out for several years. As a result, it turned out that about 1-3 percent of babies with an increased titer of certain antibodies to neurospecific antigens, in particular proteins, were at risk for cerebral palsy, others later experienced mental retardation. So scientists with the help of antibodies were able to prove that many problems are rooted in early disorders of brain activity, which are signaled by certain antibodies. The next step was to study this problem in adults.

Scientists have summed up a serious theoretical basis for their reasoning. "We proceeded from the fact that there is a single regulatory system in the human body, and we have never separated the nervous, immune and endocrine systems," says Vladimir Sherstnev. This thesis, put forward in the XIX century by Russian scientists, was forgotten for a long time, and only in the 80s of the last century in the USA announced the existence of a new science, psychoneuroimmunology. The second principle underlying the new concept was the thesis that the birth, development and death of an organism are interrelated processes. Therefore, the "molecular wave" associated with some process inevitably covers the entire brain. As it turned out, the same molecules are involved simultaneously in the processes of cell development, growth and death. The same molecules, in particular neurospecific proteins, with different contents in cells perform a different role. "In low concentrations, these are factors with neurotrophic activity that support certain groups of neurons," says Gruden. "But if the content or expression of these proteins increases and their intracellular concentration increases, they perform a completely different function - they cause cell death." It turns out that at the molecular level, the body does not need to have "killers" and "helpers". The same molecules act like soldiers: what task was given, what genetic program worked, such a function they perform.

"We went further and discovered that there are so-called intersystem factors that can perform a variety of functions - for example, work in the brain and simultaneously participate in the differentiation of tumor cells," says Marina Gruden. - At first, it was very difficult for me to explain to doctors why, for the diagnosis of encephalopathy, we chose a factor whose work was investigated in human leukemia, and now we are studying its work in the brain in animals and humans. Although, I must admit, I myself was surprised to find this factor in the hippocampus in laboratory animals. I even had a thought: "What is he doing here?" But the reason was simple: he acts in accordance with the task that he received in the body."

Insulin test Scientists have based their test systems on a number of factors.

For example, when testing Parkinson's disease, they used antibodies to insulin, changes in the metabolism of which no one has ever associated with neurodegenerative diseases. It just never occurred to anyone to look at what happens with the production of antibodies to insulin. Scientists stumbled upon an amazing result by accident. When investigating Parkinson's disease, scientists first used a very expensive protein as a marker. The experiments were costly, and scientists tried to find a cheaper factor. We tried insulin, which is now produced for the needs of diabetics in huge quantities and therefore is inexpensive. And then it turned out that it can serve as a marker.

Creating test systems, scientists worked with antibodies of the first and second order. "By how quickly the "response" antibodies to primary antibodies appear, one can judge the level of their production," says Marina Gruden. - If this level drops sharply or increases, it can be assumed that there has been a malfunction of the body system." It is very important to understand at what stage of the disease the patient is. "If he has a primary system failure, then most likely he will not need harsh therapy," Vladimir Sherstnev believes. - Relaxing procedures, swimming in the pool and so on will help a person. But if it is at an advanced stage, it can and should be treated." Test systems include proteins that are directly related to the work of the brain. The conclusions reached by scientists often seem paradoxical. For example, there are proteins whose constant increase in expression during the development of brain diseases indicates that there have been dramatic changes in the natural balance between the cells being born and dying. Usually, doctors in such cases prescribe drugs to patients that reduce cell death. However, knowledge of the complex mechanics of the processes dictates a different approach to treatment. "Rather, it is necessary to stimulate the birth of new cells, rather than block their natural death," says Marina Gruden.

The scientists compared nine molecular indicators with sixty clinical parameters of a patient with encephalopathy and subjected their data to special mathematical processing. As a result, a disease formula of six parameters appeared. This formula was based on research data. The researchers obtained a fairly strict quantitative ratio of indicators of various antibodies to special proteins, indicating a certain stage of the development of the disease. Now they are going to create a computer program based on this model for clinicians, with which it would be possible to process the analysis data. The future program will give the doctor a diagnosis and prognosis of the disease, as well as help calculate the necessary doses of drugs.

"Now, with a certain degree of confidence, we can give a person not only a forecast for 3-5 years, but also advice," says Marina Gruden. - When we talk about genetic diseases, there is, frankly, little that can be changed. But if Alzheimer's disease is acquired, if stroke has the same origin… In this case, you can do a lot. Having changed his life at least a little, having learned to rest and relax, receiving the right therapy, a person can give himself an additional 10-15 years of health." A huge gift, if we recall the average life expectancy in our country.

Portal "Eternal youth" www.vechnayamolodost.ru05.11.2008

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