Innovative technologies in laboratory diagnostics

Medicine of the presentSvetlana Sinyavskaya, STRF.ru
On October 30, the scientific and practical conference "Innovative technologies in Laboratory Diagnostics" was held at the Research Institute of Physico-Chemical Medicine of the FMBA.

The organizer of the event – the research and production company "Litech" - presented its latest developments in laboratory diagnostics of various diseases. And even if a medical and preventive institution (LPU) does not yet have the opportunity to purchase this or that diagnostic equipment, doctors have learned which tests can be outsourced.

Modern diagnostics means not just the detection of the disease at an early stage, but rather the statement of the risk of a disease that has not yet begun. What is happening now in the so-called personalized and, let's pay attention, already practical medicine, impresses even professionals! "It is not the measurement of parameters that is not available for practice, but some kind of algorithmization of what reasons to prescribe tests and how to interpret them correctly," Vadim Markovich Govorun, president of NPF Litech and deputy director of the Research Institute of Physico–Chemical Medicine of Roszdrav, told the assembled doctors. The solution of this difficult task will largely depend on the union of the doctor and the service clusters (manufacturers of diagnostic equipment, pharmaceutical industry, etc.). The Union, sanctified not only by profit, but also by the desire to make the Patient healthy. It's no joke – the cause of death from competently – from the point of view of medicine of the XX century – prescribed drugs in the United States ranks fifth. To find out how a particular medication acts on a particular person, you can use molecular diagnostics. "In clinical practice, molecular diagnostics not only provides the principle of evidence–based medicine, but also allows you to control the development of the disease, diagnose socially significant diseases at early stages," Vadim Govorun explained the need to switch to medicine of the XXI century.

I will not undertake to describe the devices with which doctors intend to prolong our active life (the golden billion is getting old!), but I can say that science fiction writers who intend to surprise readers with a miracle diagnostician implanted in a person can put the keyboard aside - perhaps very soon their wild dreams will become reality. For example, I was convinced at the conference that it is not far from a laboratory on a chip offered by the NPF Litech to a cyborg (combining a kind of laboratory with a patient). Yes, of course, it is possible to talk for a long time and not unreasonably about the lag of Russian medicine from Western medicine, but we also have separate islands of progress. For example, in September of this year, the FDA (the American Food and Drug Administration) approved a new test to determine the risk of ovarian cancer in women with a detected tumor in the pelvis. At the conference, Vadim Govorun spoke about the initiative of NPF Litech to create a similar test and invited clinicians to cooperate to conduct appropriate tests. For patients, participation in the program will be free of charge.

Vadim Govorun also introduced doctors to the new profiles of the NPF "Litech": "Men's Health", "Maternity Hospital" and "Hepatitis and cirrhosis". Knowing these profiles, the doctor can, for example, determine the nature of prostatitis, which means saving the patient time and money.

A little routineWhat needs to be done in order for the islands of progress to become continents?

Have innovative technologies been introduced into the routine practice of a clinician? With such a report ("Introduction of new methods of laboratory research of infectious diseases into routine practice") Elena Ilyina, Head of the Laboratory of Molecular Genetics of Microorganisms of the Research Institute of Physico-Chemical Medicine of Roszdrav, Candidate of Biological Sciences, spoke. According to her, DNA chips are already used in the clinic to indicate pathogens of bacteremia, enterococcal infection, tuberculosis (in ecology they are used to assess the degree of contamination of water, soil, air; in the food industry to assess the quality of food products). "The created DNA micro-matrices make it possible to identify 50 species of bacteria, mainly anaerobes and microaerophiles, colonizing human mucous membranes." Elena Ilyina also told about the results of the clinical use of these DNA micro-matrices. They, for example, "allowed us to establish the leading role of anaerobic flora in the formation of bacterial vaginosis in women and nonspecific balanoposthitis in men. The use of DNA micro-matrices for the effectiveness of the therapy was particularly relevant." In particular, because the researchers have slightly revealed the secret of genetically determined drug resistance. "Our laboratory has developed a method for quickly determining the resistance of tuberculosis strains to anti–tuberculosis drugs," Elena Ilyina added. "The method is based on the study of resistance markers (mutations in the genome of a bacterium associated with its resistance) to a particular drug."

Today, such diagnostics are used on the technological line of proteogenomic monitoring of gonococcus in the Central Research Institute of Roszdrav and the technological line of genetic monitoring of tuberculosis in the Central Research Institute of Tuberculosis of the Russian Academy of Medical Sciences. Integrated circuits of genomic-proteomic analysis of pneumococcus, staphylococcus, hepatitis B and C viruses have been worked out; similar technological approaches for nosocomial infections are being developed; genomic-proteomic analysis of the causative agent of syphilis Treponema pallidum is being developed, Elena Ilyina said. As she told the correspondent STRF.ru Anna Ermak, head of the prenatal diagnostics department of the Family Planning and Reproduction Center (CPSIR), "we are interested in pushing the authorities to purchase such diagnostic equipment, but now we will be able to refer patients to the NPF "Litech"for the necessary analysis".

And what is the inheritance?As you can see, even a medicine can be harmful if the genes "want" it.

Eduard Generozov, Candidate of Biological Sciences and employee of the Federal State University of the Institute of Physico-Chemical Medicine of Roszdrav, offers to live with them in friendship, who spoke at the conference with the report "Human genetic typing. Personalized medicine today."

He drew the attention of those present to the fact that genetic research not only allows this very personalized medicine to be, but also raises a number of ethical questions. And if there are no objections to adequate monitoring of the use of drugs, against studying the phenotypic manifestations of early stages of diseases using proteomic and other diagnostic technologies, then genetic analysis to determine the risk of developing socially significant diseases causes an ambiguous reaction in society.

And yet… Just think, if yesterday it was believed that only rare monogenic diseases (1:15 000-1:40000) associated with a mutation of one gene and a high penetrance of the mutant allele were genetically determined (in medicine, this means a high probability of the disease, but not its severity), now experts are talking about the genetic conditionality of multifactorial diseases, diseases widely common, with an unclear type of inheritance and low penetrance of the mutant allele. Until recently, the role of genetics in preventive medicine was reduced to the registration of families of patients with monogenic hereditary pathologies, but the possibilities of modern genetics are much wider, Eduard Generozov noted and gave a table in which an analysis of the concordance (presence of a certain sign) of the development of the disease in monozygotic and dizygotic twins is given:

What is the proportion of heredity in "non-genetic" diseases? Here are the results of a study conducted at the Royal Stockholm Institute and involving more than 11 million people with the analysis of family data since 1932: the risk for women in the development of coronary heart disease increases by 43% compared to the norm if her mother suffered from such a disease, and by 17% – if her father suffered from such a disease. For men, such indicators are 55% and 41%, respectively. If both parents were ill, then the risk of the disease becomes even higher and is more than 80% regardless of gender. "But it's not enough to see a pattern. It is necessary to know its mechanisms, – said Eduard Generozov. – Are the genetic components of these diseases known? In many ways, yes! The opportunity to better understand these mechanisms has emerged as a result of the success of genomic projects. Surprisingly, the identity of the genomic DNA of two individuals is 99.9%. Only 0.01% of the differences are responsible for all the diversity associated with both external data and other indicators, including predisposition to certain diseases."

The most common type of genomic variation is point nucleotide polymorphism, or SNP (single nucleotide polymorphisms). "Simply put, SNPs are minor changes in the structure of genes that can lead to significant changes in their properties, and in the medical sense – to the development of the disease," said Eduard Generozov. And he added that polymorphisms are not an immediate and obligatory cause of the development of the disease, but may cause a greater or lesser risk of its development. Eduard Generezov reminded the doctors about the "SNP-express" test (the format of reagent kits for the analysis of genetic polymorphisms by PCR), as well as about current directions for genetic analysis. First of all, these are cardiovascular diseases, which occupy the first place in the cause of mortality, neurodegenerative diseases, metabolic diseases. Eduard Generozov also noted that if the nature of nutrition can aggravate a genetic defect, then why not prevent the phenotypic expression of this defect with the help of nutrition? The results of the research presented by the speaker show that the formulation of the question is correct.

He reminded the doctors that there are already minimal diagnostic profiles for assessing the risk of venous thrombosis, hypertension, for the study of lipid metabolism disorders and said that the Research Institute has "the possibility of carrying out large-scale genetic studies in groups including more than 300 nucleotide polymorphisms, informative in various nosological groups, primarily such as cardiovascular, oncological and metabolic diseases.

In general, from an interesting lecture by Eduard Generozov, I learned that

• genetic factors play a role in the formation of predisposition to many multifactorial diseases;
• many of these factors can be analyzed today;
• information about the presence of an unfavorable genotype makes it possible to prevent the development of the disease or to identify it at an early stage;
• information about the genotype can be useful when choosing the optimal therapy regimen;
• genetic analysis of the selected variants of genes is enough to do only once;
• genetic analysis data can be informative when planning a family.

Was there a boy?The head of the Laboratory of Clinical Genetics of the Kulakov Federal State University Scientific Center of Obstetrics, Gynecology and Perinatology of Rosmedtechnology (NC AGiP), Doctor of Medical Sciences, Professor Vladimir Bakharev also spoke for family planning.

His report is "Congenital malformations and hereditary diseases at the present stage. Prenatal screening of congenital fetal pathology" – most of the conference participants were waiting for: probably, there will always be more questions in this area than answers.

But first, a little statistics. According to Vladimir Bakharev, the frequency of congenital and hereditary pathology in the population does not change and is on average 5% of the number of newborns. Of these, malformations account for 2.5%, chromosomal abnormalities – 0.8% and monogenic diseases - 1%. These figures may mean little to a non–specialist, but here are other data - in the structure of perinatal mortality, congenital and hereditary pathology ranks second or third. On average, 3-3.5 thousand children with severe disabling diseases are born annually per 10 million population (taking into account their average life expectancy in a region with a population of 10 million, there are about 100,000 such patients on medical care and social assistance).

As a rule, all these diseases can be detected during pregnancy. For this purpose, mandatory prenatal biochemical screening has been introduced in a number of regions (for example, in Moscow): it is non-invasive, does not cause complications and is suitable for mass use. The main thing is that screening allows you to identify a group for subsequent invasive prenatal diagnosis (examination of fetal material – chorionic villi cells, placenta, amniotic fluid and blood). The professor reminded the doctors about the algorithm of prenatal monitoring for trimesters of pregnancy and stressed the absolute importance of ultrasound screening. In his opinion, ultrasound should be done three times during pregnancy (9-11; 17-20; 30-32 weeks, which is somewhat different from the recommendations of Order No. 457 of the Ministry of Health and Social Development). Of course, the quality of ultrasound depends primarily on the qualifications of the staff. "In Russia and in developed countries, according to sample studies, the detection of congenital malformations in first–level institutions is 20%, second-level - 55%, in perinatal centers – 90%. In the NC AGiP, this figure is 94%."

According to Vladimir Bakharev, the following indications are available for medical and genetic counseling:

• the birth of a child with hereditary diseases or congenital malformations;
• the presence of a chromosomal rearrangement, hereditary disease or malformation in one of the spouses;
• consanguineous marriage;
• the age of the mother is over 35 years old;
• adverse effects of environmental factors in early pregnancy (infectious diseases, massive drug therapy, rengenodiagnostic procedures, occupational hazards);
• the presence of spontaneous miscarriages, stillbirths of unknown origin, primary amenorrhea; primary infertility of spouses (after exclusion of gynecological pathology);
• the onset of pregnancy as a result of the use of assisted reproductive technologies.

"Unfortunately, mostly those who have already had some problems come to us. Our center is rarely visited before they want to have a child. It's a pity!" – Professor Vladimir Bakharev concluded his lecture.

So far, it cannot be said that the technologies presented at the conference at the NPF Litech have been massively implemented, and they are known only to doctors seeking. But I want to believe that thanks to such people and similar events, a new quality of life will become habitual faster.

The frequency of occurrence of some congenital and hereditary pathologyPathology

The main causes of perinatal mortality and morbidity of newborns in the Russian Federation in 2006Reason

Additional information about genetic certification and new diagnostics can be found on the websites www.lytech.ru , www.pynny.ru ; information system on medically significant nucleotide polymorphisms of the human genome is presented on the website www.genepassport.ruPortal "Eternal youth" http://vechnayamolodost.ru

06.11.2009