RU2587785C1 - Method for prediction of sensitisation to formaldehyde in adolescents - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to laboratory diagnosis, and can be used in diagnosis of organism sensitisation to formaldehyde. For this purpose, method includes determining relative content of autoantibodies to membrane antigens of pulmonary parenchyma LuM and to β2-glycoprotein. Diagnostic index is calculated by formula: y=exp(-0.222+0.004×auto-AT β2-GP I+0.026×auto-AT LuM)/(1+exp(-0.222+0.004×auto-AT β2-GP I+0.026×auto-AT LuM)), where: y is a diagnostic coefficient, -0.222 is a constant, 0.004 and 0.026 are predictor coefficients. Predictors used are auto-AT LuM - relative content of auto-AT to membrane antigens of pulmonary parenchyma LuM, auto-AT β2-GP I - relative content of auto-AT to β2-glycoprotein I. If y is less than 0.5 is determined, absence of organism reaction to formaldehyde, and absence of organism sensitisation to formaldehyde is predicted. If y is more than 0.5 reaction to formaldehyde is considered to be positive and a body sensitisation to formaldehyde is predicted.

EFFECT: using given method enables to predict sensitisation to formaldehyde on basis of immunological values of auto-AT LuM and auto-AT β2-GP I.

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Description

The invention relates to medicine, namely to preventive medicine. The invention can be used in the diagnosis of changes in immunological parameters during sensitization of the body with formaldehyde.

According to the World Health Organization, about 20% of the risk of health problems falls on the state of the environment. Environmental pollution with various chemical compounds has a negative impact on public health, including increasing the likelihood of changes in immunity and, as a result, causes an increase in morbidity [1, 2, 3, 4, 5,]. The children's population is most sensitive to external factors, since the body is exposed to the negative effects of the environment when detoxification systems, adaptive mechanisms and the immune system are still immature. Moreover, adolescence refers to one of the critical periods of the formation of the immune system in ontogenesis, therefore, the influence of exogenous factors on the immune system at this time becomes very important and can affect the processes of the formation of the immune system.

A variety of chemical compounds, including formaldehyde, are thrown into the air by enterprises in the chemical, woodworking, and pulp and paper industries. According to the degree of danger of exposure to the body, formaldehyde belongs to highly hazardous chemicals (hazard class 2). It has a general toxic, sensitizing and allergenic effect on the body.

In Russia, about a quarter of the population suffers from some form of allergy, and in industrial cities and ecologically unfavorable regions this indicator is more than double [6, 7]. It was previously established that the incidence of diseases such as allergic rhinitis and bronchial asthma among children living in industrial cities of Eastern Siberia is 28-36% [8]. In recent years, a number of authors have noted a significant increase in the frequency of development of allergic intolerance to various chemicals, including those which are quite inert [9].

To diagnose the sensitization of the body to various substances from laboratory methods, a method is known for determining the levels of specific immunoglobulins E in blood serum and a test for the natural migration of leukocytes [10, 11].

There is a method for diagnosing the body’s sensitization to chemical compounds, which is based on a change in the rate of leukocyte migration with the addition of hematractants - the inhibition of leukocyte migration (RTML) [11, 12,].

To carry out this method under sterile conditions, a leukemia suspension is isolated from the blood, incubated at a temperature of 37 ° C for 24 hours in test tubes with and without antigen (control).

Then, the boundaries of leukocyte migration are determined using an eyepiece micrometer and the migration index relative to the control is calculated.

The disadvantage of this technique is its complexity, duration, the need for sterile conditions. In addition, in the applied method, the isolation of leukocyte suspension must be carried out in the next few hours after blood sampling, which makes it inaccessible for screening examinations of the population from remote areas.

The prototype is a method for determining the sensitization of the body, in which for guinea pigs use leukemix of guinea pigs and human serum [13]. The disadvantage of this invention is also the high complexity, the duration of the study, the presence of sterile conditions and guinea pigs. These shortcomings reduce the value of this diagnosis.

The objective of the invention is to develop a method that allows to predict sensitization to formaldehyde and suitable for use in screening examinations of urban and rural populations, as well as residents of remote areas by health care institutions and scientific organizations.

The problem is solved by calculating a diagnostic indicator that predicts the sensitization of the body to formaldehyde, using immunological indicators.

The method is as follows: in a patient on an empty stomach, blood is taken from the cubital vein using vacuum systems with an activator of blood coagulation (to obtain serum). Using the semiquantitative ELISA method, the relative content of autoantibodies (auto-antibodies) of the IgG class to membrane antigens of the lung parenchyma - LuM and to β2-glycoprotein I is determined [14, 15].

The obtained patient examination results are substituted into the equation:

wherein

y is the diagnostic coefficient,

-0.222 - constant,

0.004 and 0.026 are the predictor ratios,

Auto-AT LuM - the relative content of auto-AT to membrane antigens of the lung parenchyma LuM;

auto-AT β2-GP I - the relative content of auto-AT to β2-glycoprotein I.

if y is less than 0.5, a conclusion is drawn that there is no reaction of the body to formaldehyde and the absence of sensitization of the body to formaldehyde is predicted; if y is more than 0.5, the reaction to formaldehyde is considered positive and the body is sensitized to formaldehyde.

The claimed method differs from the prototype in that the assessment of the body's response to formaldehyde is not carried out by a direct method for determining the RTML index for this chemical compound, but is calculated by changing only the immunological parameters of the blood. It is less labor intensive, does not require sterile conditions for its implementation, can be performed in the delayed period after blood collection.

Changes in the content of LuM autoantibodies to membrane antigens of the lung parenchyma make it possible to identify dystrophic and atrophic changes in the parenchyma, which reflect the onset of pathological processes, regardless of the causes that cause them. An increase in the level of autoantibodies to β2-glycoprotein I is a marker of both the phospholipid syndrome and the active infectious process. No data were found in the medical literature on the use of a combination of indicators such as the content of autoantibodies to β2-glycoprotein I and LuM in the blood to evaluate the sensitization of the body to formaldehyde.

A method for predicting the body’s sensitization to formaldehyde depending on changes in only immunological parameters with these distinguishing features has not been found in the medical, scientific and patent literature, thus, the proposed method meets the criteria of the invention of “Novelty”.

Using the mathematical method, a combination of indicators such as the relative content of auto-antibodies to membrane antigens of the lung parenchyma LuM and β2-glycoprotein I, allowed us to obtain a new result that clearly does not follow from the prior art. Thus, the claimed invention meets the criterion of "Inventive step".

The proposed method was developed during a survey of adolescents. A total of 92 people were examined, who, according to the results of RTML assessment, were divided into two groups: children with an inhibition index of leukocyte migration to formaldehyde outside the reference values (group I, n = 42), children with an index of inhibition of leukocyte migration in the normal range (group II , n = 50). The relative content of auto-antibodies to membrane antigens of the lung parenchyma LuM and to β2-glycoprotein I was studied in all children.

Using logistic regression of the personalized results of the study of the studied groups, we obtained an equation expressing the relationship of the variable (response to formaldehyde in RTML) with indicators considered as predictors, in which the following were used as predictors: the relative content of autoantibodies to membrane antigens of the lung parenchyma (auto-AT LuM) and the relative content of autoantibodies to β2-glycoprotein I (auto-AT β2-GP I).

For this model, 2 × log (Likelihood) = 101.7062, χ ² = 24.13378, df = 2, p = 0.0000058.

The statistical characteristics of the studied groups are presented in table 1, which includes the following laboratory data: arithmetic mean (Mean), median (Me), 25th and 75th percentiles (Q25-Q75), standard deviation (Std) and error medium (SE mean).

The ratio of prognosis and outcome (there is a reaction to formaldehyde or not) in the group of people who are and are not included in the training group is presented in table 2.

Diagnostic Efficiency Assessment

We calculated the prognostic indicator and calculated the coefficients: sensitivity, specificity. The sensitivity of the proposed method was 57.1%, specificity - 94.0%.

Example 1. Patient R. (girl, 16 years old) lives in an industrial city, where formaldehyde is detected in atmospheric air and residential air. The values of immunological parameters: Auto-AT to β2-GP I - -19.7%, Auto-AT LuM - -34.2%.

The diagnostic indicator of immunoreactivity is calculated by the formula:

The value of the diagnostic indicator in patient R. is in the range of less than 0.5 (no reaction to formaldehyde).

Conclusion: no sensitization to formaldehyde in the patient.

Example 2. Patient S. (girl, 14 years old) lives in an industrial city, where formaldehyde is detected in atmospheric air and residential air.

The values of immunological parameters: Auto-AT to β2-GP I - -7.7%, Auto-AT LuM - 8.1%.

The diagnostic indicator of immunoreactivity is calculated by the formula:

The value of the diagnostic indicator in patient C. is in the range of more than 0.5 (there is a reaction to formaldehyde).

Conclusion: the patient may sensitize to formaldehyde.

Example 3. Patient B. (boy, 15 years old) lives in an industrial city, where formaldehyde is detected in atmospheric air and residential air. The values of immunological parameters: Auto-AT to β2-GP I - 20.5%, Auto-AT LuM - 9.9%.

The diagnostic indicator of immunoreactivity is calculated by the formula:

The value of the diagnostic indicator in patient B. is in the range of less than 0.5 (no reaction to formaldehyde).

Conclusion: no sensitization to formaldehyde in the patient.

Example 4. Patient P. (boy, 14 years old) lives in an industrial city where formaldehyde is detected in the air and air of residential premises. The values of immunological parameters: Auto-AT to β2-GP I - 1.8%, Auto-AT LuM - 54.1%.

The diagnostic indicator of immunoreactivity is calculated by the formula:

The value of the diagnostic indicator in patient P. is in the range of more than 0.5 (there is a reaction to formaldehyde).

Conclusion: the patient may sensitize to formaldehyde.

Literature

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Claims (1)

A method for predicting sensitization to formaldehyde in adolescents, including a laboratory blood test, characterized in that the blood serum determines the relative content of autoantibodies (auto-antibodies) of the IgG class to lung membrane parenchyma antigens - LuM and β2-glycoprotein I, calculate the diagnostic coefficient by the formula :
y = exp (-0.222 + 0.004 × auto-AT β2-GP I + 0.026 × auto-AT LuM) / (1 + exp (-0.222 + 0.004 × auto-AT β2-GP I + 0.026 × auto-AT LuM) ),
Where:
y is the diagnostic coefficient,
-0.222 - constant,
0.004 and 0.026 are the predictor ratios,
as predictors use:
Auto-AT LuM - the relative content of auto-AT to membrane antigens of the lung parenchyma LuM;
auto-AT β2-GP I - the relative content of auto-AT to β2-glycoprotein I,
when y is less than 0.5, a conclusion is drawn that there is no reaction of the body to formaldehyde and the absence of sensitization of the body to formaldehyde is predicted, when y is more than 0.5, the reaction to formaldehyde is considered positive and the sensitization of the body to formaldehyde is predicted.