Bruton's disease immunology. Bruton's disease: etiology, causes, symptoms and treatment features

Genetic pathologies are rare congenital diseases that are difficult to predict in advance. They occur even at the moment when the formation of the embryo occurs. Most often they are transmitted from parents, but this is not always the case. In some cases, gene disorders occur on their own. Bruton's disease is considered one of these pathologies. It belongs to the primary This disease was discovered recently, in the middle of the 20th century. Therefore, it has not been fully studied by doctors. It is quite rare, only in boys.

Bruton's disease: a history of study

This pathology refers to X-linked chromosomal abnormalities transmitted at the genetic level. Bruton's disease is characterized by disturbances in its main symptom is susceptibility to infectious processes. The first mention of this pathology falls on 1952. At that time, the American scientist Bruton studied the anamnesis of a child who fell ill more than 10 times at the age of 4. Among the infectious processes in this boy were sepsis, pneumonia, meningitis, inflammation of the upper respiratory tract. When examining the child, it was found that there were no antibodies to these diseases. In other words, no immune response was observed after the infections.

Later, in the late 20th century, Bruton's disease was studied again by doctors. In 1993, doctors were able to identify a defective gene that causes impaired immunity.

Causes of Bruton's disease

Agammaglobulinemia (Bruton's disease) is most often hereditary. The defect is considered a recessive trait, so the probability of having a child with a pathology is 25%. The carriers of the mutant gene are women. This is due to the fact that the defect is localized on the X chromosome. However, the disease is transmitted only to the male sex. The main cause of agammaglobulinemia is a defective protein that is part of the gene encoding tyrosine kinase. In addition, Bruton's disease can be idiopathic. This means that the reason for its appearance remains unclear. Among the risk factors that affect the genetic code of the child, there are:

Alcohol and drug abuse during pregnancy.
Psycho-emotional stress.
Exposure to ionizing radiation.
Chemical irritants (harmful production, unfavorable ecology).

What is the pathogenesis of the disease?

The mechanism of disease development is associated with a defective protein. Normally, the gene responsible for encoding tyrosine kinase is involved in the formation of B-lymphocytes. They are immune cells that are responsible for the humoral defense of the body. Due to the failure of tyrosine kinase, B-lymphocytes do not fully mature. As a result, they are not able to produce immunoglobulins - antibodies. The pathogenesis of Bruton's disease is the complete blocking of humoral protection. As a result, when infectious agents enter the body, antibodies to them are not produced. A feature of this disease is that the immune system is able to fight viruses, despite the absence of B-lymphocytes. The nature of the violation of humoral protection depends on the severity of the defect.

Bruton's disease: symptoms of pathology

Pathology first makes itself felt in infancy. Most often, the disease manifests itself by the 3-4th month of life. This is due to the fact that at this age the child's body ceases to protect maternal antibodies. The first signs of pathology may be a painful reaction after vaccination, skin rashes, infections of the upper or lower respiratory tract. Nevertheless, breastfeeding protects the baby from inflammatory processes, since mother's milk contains immunoglobulins.

Bruton's disease manifests itself by about 4 years of age. At this time, the child begins to contact with other children, attends kindergarten. Among infectious lesions, meningo-, strepto- and staphylococcal microflora predominates. As a result, children may be prone to purulent inflammation. The most common diseases include pneumonia, sinusitis, otitis media, sinusitis, meningitis, conjunctivitis. With untimely treatment, all these processes can turn into sepsis. Also, a manifestation of Bruton's disease can be dermatological pathologies. Due to a reduced immune response, microorganisms multiply rapidly at the site of wounds and scratches.

In addition, the manifestations of the disease include bronchiectasis - pathological changes in the lungs. Symptoms are shortness of breath, pain in the chest, sometimes hemoptysis. It is also possible the appearance of inflammatory foci in the digestive organs, the genitourinary system, on the mucous membranes. Swelling and pain in the joints are periodically observed.

Diagnostic criteria for the disease

The first diagnostic criterion should include frequent morbidity. Children suffering from Bruton's disease suffer more than 10 infections per year, as well as several times during the month. Diseases can repeat or replace each other (otitis media, tonsillitis, pneumonia). When examining the pharynx, there is no hypertrophy of the tonsils. The same applies to palpation of peripheral lymph nodes. You should also pay attention to the reaction of the baby after vaccination. Significant changes are observed in laboratory tests. In the KLA, there are signs of an inflammatory reaction (increased number of leukocytes, accelerated ESR). At the same time, the number of immune cells is reduced. This is reflected in the leukocyte formula: a small number of lymphocytes and an increased content of neutrophils. An important study is the immunogram. It reflects the decrease or absence of antibodies. This sign allows you to make a diagnosis. If the doctor has doubts, a genetic examination can be performed.

Differences between Bruton's disease and similar pathologies

This pathology is differentiated from other primary and among them - Swiss-type agammaglobulinemia, HIV. In contrast to these pathologies, Bruton's disease is characterized by a violation of only humoral immunity. This is manifested by the fact that the body is able to fight viral agents. This factor differs from Swiss-type agammaglobulinemia, in which both humoral and cellular immune responses are impaired. To conduct a differential diagnosis with DiGeorge syndrome, it is necessary to make (thymus aplasia) and determine the calcium content. To exclude HIV infection, palpation of the lymph nodes, ELISA is performed.

Methods for the treatment of agammaglobulinemia

Unfortunately, it is impossible to completely defeat Bruton's disease. Treatment methods for agammaglobulinemia include substitution and symptomatic therapy. The main goal is to achieve a normal level of immunoglobulins in the blood. The amount of antibodies should be close to 3 g/l. For this, gamma globulin is used at the rate of 400 mg/kg of body weight. The concentration of antibodies should be increased during acute infectious diseases, as the body cannot cope with them on its own.

In addition, it is carried out. Most often, antibacterial drugs "Ceftriaxone", "Penicillin", "Ciprofloxacin" are prescribed. Skin manifestations require topical treatment. It is also recommended to wash the mucous membranes with antiseptic solutions (irrigation of the throat and nose).

Prognosis for Bruton's agammaglobulinemia

Despite lifelong replacement therapy, the prognosis for agammaglobulinemia is favorable. Continuous treatment and prevention of infectious processes reduce the incidence to a minimum. Patients usually remain able-bodied and active. With the wrong approach to treatment, complications can develop up to sepsis. In the case of advanced infections, the prognosis is poor.

Prevention of Bruton's disease

In the presence of pathology in relatives or suspicion of it, it is necessary to conduct a genetic examination during the first trimester of pregnancy. Also, preventive measures should include exposure to air, the absence of chronic infections and harmful effects. During pregnancy, the mother is contraindicated in stress. Secondary prevention includes vitamin therapy, the introduction of gamma globulin, a healthy lifestyle. It is also important to avoid contact with infected people.

One of the diseases that are inherited is characterized by agammaglobulinemia. Also known as agammaglobulinemia, Bruton's disease. This is one of the types of immunodeficiency. The disease is caused by a mutation in the gene encoding Bruton's tyrosine kinase. Agammaglobulinemia is characterized by an almost complete absence, which protect the human body from various bacteria and.

The first mention of the disease agammaglobulinemia, which was recorded in the United States by pediatrician Ogden Bruton, dates back to 1952. The physician happened to meet an eight-year-old boy who, over the last four years of his life, had pneumonia fourteen times, sinusitis and otitis media did not bypass him, suffered meningitis and. After a medical examination, no antibodies were found in the child.

In 1993, scientists, after conducting research, announced the causes of this disease. It turned out that X-linked agammaglobulinemia arises due to mutations in the gene for non-receptor tyrosine kinase, which was later called Bruton's tyrosine kinase. Photos of Bruton's disease were also presented.

Characteristic features of the disease

What is its peculiarity, how is Bruton's disease characterized? The presence of a mutated protein in the gene is the cause of the disease. Bruton's disease is inherited through an X-linked recessive type. Agammaglobulinemia is diagnosed only in boys, as they have an XY chromosome in their DNA. Having XX chromosomes, girls cannot get sick. Even if the females are heterozygous, then the gene with the presence of the mutation is replaced by the normal one.

Bruton's disease can be detected in one boy out of 250,000. Women, on the other hand, can only be carriers of such a gene and pass it on to their sons.

The first symptoms of Bruton's disease begin before the age of 1 year, at about 3-6 months. During this period, the level of antibodies received from the mother in the baby's blood falls. What will be the manifestations and signs of agammaglobulinemia?

One of the main signs of Bruton's disease is the presence of chronic and recurrent infections caused by pyogenic bacteria. These can be microorganisms of pneumococci, staphylococci, Haemophilus influenzae and others. They have the ability to cause purulent inflammation.

The disease of the child is associated with the ENT organs, the baby may have problems with the skin and subcutaneous fat, disorders in the gastrointestinal tract, respiratory tract.

A boy with Bruton's disease may be physically smaller than his peers who are healthy. This is provoked by slow growth and recurrent infections.

He can get pneumonia, otitis media, sinusitis, meningitis, encephalitis. In a child suffering from agammaglobulinemia, most often, autoimmune diseases, oncological pathologies, disorders in the structure of connective tissue (arthritis of large joints). Vaccination against polio or hepatitis B leads to the development of these diseases. During the examination, the small size of the lymph nodes and tonsils, or their complete absence, can be detected.

Diagnostics

In order to identify Bruton's disease, a number of studies need to be carried out. Diagnosis of agammaglobulinemia is recommended as early as possible to prevent the development of secondary infections and reduce the number of deaths from the disease. Mandatory examination of the patient, laboratory tests, x-rays.

The results, carried out in the laboratory, show that there are no gamma globulins in the proteinogram. There is a hundred-fold decrease in the levels of Ig A and Ig, and Ig G - ten times. Less than the norm and the number of B-lymphocytes. At the stage of pregnancy planning, it is recommended to conduct a molecular genetic examination, which will detect the presence of a defective gene encoding non-receptor tyrosine kinase.

Radiography can reveal the absence of tonsils or their underdevelopment, the pathology of the lymph nodes, as well as changes in the spleen. Children over the age of five need to have lung function tests (bronchoscopy) done in order to diagnose a violation in their work in time. Endoscopy and colonoscopy are also used to assess the extent and progression of inflammatory bowel disease.

Treatment and prognosis

The whole essence of the treatment of Bruton's disease is supportive therapy, that is, gamma globulin preparations are administered to the patient. The dose is selected individually, but the result should be a serum concentration of 3 grams / liter.

Throughout life, medications are used to maintain the functioning of the immune system. That is, the patient is injected with antibodies that his body cannot produce. Therapy should begin at 9 to 12 weeks of age. With exacerbations of infectious diseases, antibiotics are used to remove the symptoms of Bruton's disease. Preparations based on penicillins, cephalosporins, sulfonamides can be used.

With constant therapy with immunoglobulins and antibiotics, agammaglobulinemia has a favorable prognosis. If you violate the mode of administration of gamma globulins and untimely use of antibacterial drugs, this can lead to serious consequences. There is a possibility of the development of a pathological process or the onset of death.

Prevention of agammaglobulinemia

Bruton's disease is characterized by a genetic nature, so prevention is not possible here. If there is a family history of this disease, it is recommended that couples undergo an examination and consult a geneticist.

If a child has agammaglobulinemia, measures must be taken to prevent complications and recurrence of infections.

It can be:

use only inactivated vaccine;
compliance with adequate treatment of diseases;
prophylactic, long-term antibiotic therapy.

Bruton's disease, or Bruton's agammaglobulinemia, is a hereditary immunodeficiency that is caused by mutations in the gene encoding Bruton's tyrosine kinase. The disease was first described by Bruton in 1952, after whom the defective gene was named. Bruton's tyrosine kinases are critical in the maturation of pre-B cells to the differentiation of mature B cells. The Bruton tyrosine kinase gene was found on the long arm of the X chromosome in the band from Xq21.3 to Xq22; it consists of 37.5 kilobases with 19 exons that encode 659 amino acids; it is these amino acids that complete the formation of cytosolic tyrosine kinase. In this gene, 341 unique molecular events have already been recorded. In addition to mutations, a large number of variants or polymorphisms have been found.

Agammaglobulinemia Bruton. The reasons

Mutations in the gene that underlie Bruton's disease interfere with the development and function of B-lymphocytes and their offspring. The basic idea is that in a healthy person, pre-B cells mature into lymphocytes. And in people with this disease, pre-B cells are either in small numbers, or they may have problems in functionality.

Agammaglobulinemia Bruton. Pathophysiology

In the absence of a normal protein, B-lymphocytes do not differentiate or do not fully mature. Without mature B-lymphocytes, antibody-producing plasma cells will also be absent. As a consequence, the reticuloendothelial and lymphoid organs in which these cells proliferate, differentiate, and store are poorly developed. The spleen, tonsils, adenoids, intestines, and peripheral lymph nodes may all be reduced in size or absent altogether in individuals with X-linked agammaglobulinemia.

Mutations in each of the gene regions can lead to this disease. The most common genetic event is the missense mutation. Most mutations result in protein truncation. These mutations affect critical residues in the cytoplasmic protein and are highly variable and evenly distributed throughout the molecule. However, disease severity cannot be predicted using specific mutations. Approximately one third of point mutations affect CGG sites, which typically contain the code for arginine residues.

This important protein is essential for the proliferation and differentiation of B-lymphocytes. Men with protein abnormalities have a complete or near complete absence of lymphocytes in their plasma cells.

Agammaglobulinemia Bruton. Symptoms and manifestations

Recurrent infections begin in early childhood and persist throughout adulthood.

The most common manifestation of Bruton's disease or Bruton's agammaglobulinemia is an increase in susceptibility to encapsulated purulent bacteria, such as Haemophilus influenzae infections, and certain Pseudomonas species. Skin infections in patients with the disease are mainly caused by group A streptococci and staphylococci, and may present as impetigo, cellulitis, abscesses, or boils.

A form of eczema that resembles atopic dermatitis may be evident, along with an increase in cases of pyoderma gangrenosum, vitiligo, alopecia, and Stevens-Johnson syndrome (due to increased drug use). Other infections that are commonly present in this disease include enterovirus infections, sepsis, meningitis, and bacterial diarrhea. Patients may also have autoimmune diseases, thrombocytopenia, neutropenia, hemolytic anemia, and rheumatoid arthritis. Persistent enterovirus infections very rarely lead to fatal encephalitis or dermatomyositis-meningoencephalitis syndrome. In addition to neurological changes, the clinical manifestations of this syndrome include edema and an erythematous rash on the skin over the extensor joints.

Men may develop unusually severe and/or recurrent otitis media and pneumonia. The most common pathogen is S pneumonia, followed by influenza B virus, staphylococci, meningococci, and moraxella catarrhalis.

In children under 12 years of age, typical infections are caused by encapsulated bacteria. Common infections in this age group include recurrent pneumonia, sinusitis, and otitis media caused by S pneumonia and influenza B virus, which are difficult to treat at this age.

In adulthood, skin manifestations become more common, usually due to staphylococcus aureus and group A streptococcus. Otitis media is replaced by chronic sinusitis, and lung disease becomes a constant problem, both in a restrictive form and in an obstructive form.

Both infants and adults can have autoimmune diseases. Typically, these disorders include arthritis, autoimmune hemolytic anemias, autoimmune thrombocytopenia, autoimmune neutropenia, and inflammatory bowel disease. Inflammatory bowel disease can be very difficult to control and often contribute to chronic weight loss and malnutrition. Diarrhea is common and is caused by Giardia or Campylobacter species. Patients are prone to enterovirus infections, including poliovirus.

Physical examination

Male infants with Bruton's agammaglobulinemia may be physically smaller than male infants without the disease due to stunted growth and development from recurrent infections.

On examination, lymph nodes, tonsils, and other lymphoid tissues may be very small or absent.

The disease is diagnosed when the child repeatedly becomes ill in the presence of various infections, otitis or staphylococcal skin infections and conjunctivitis that do not respond to antibiotic therapy. These severe infections may be associated with neutropenia.

Pyoderma gangrenosum, for example in the form of ulcers and cellulitis of the lower extremities, may also be seen in some patients.

Agammaglobulinemia Bruton. Diagnostics

Early detection and diagnosis is essential to prevent early morbidity and death from systemic and pulmonary infections. Diagnosis is confirmed by abnormally low levels or no mature B lymphocytes, and low or no μ heavy chain expression on the lymphocyte surface. On the other hand, the level of T-lymphocytes will be elevated. The ultimate determinant of disease is molecular analysis. Molecular analysis is also used for prenatal diagnosis, which can be done by chorionic villus sampling or amniocentesis when the mother is known to be a carrier of the defective gene. IgG levels less than 100 mg/dl support the diagnosis.

Rarely, the diagnosis can be made in adults in their second decade of life. This is believed to be due to a mutation in the protein rather than its complete absence.

Laboratory tests

The first step is to quantify IgG, IgM, immunoglobulin E (IgE), and immunoglobulin A (IgA). IgG levels should be measured first, preferably after 6 months of age when maternal IgG levels begin to decline. Second, IgG levels below 100 mg/dL are usually indicative of Bruton's disease. As a rule, IgM and IgA are not detected.

Once the antibody level has been determined to be abnormally low, confirmation of the diagnosis will be achieved by analysis of B-lymphocyte and T-lymphocyte markers. CD19+ B cell levels below 100 mg/dL. T cell assay values (CD4+ and CD8+) tend to increase.

Further analysis can be carried out by detecting IgG responses to T-dependent and T-independent antigens, by immunization, for example after administration of unconjugated 23-valent pneumococcal or diphtheria, tetanus and H influenza type B vaccines.

Molecular genetic testing can establish an early confirmation of the diagnosis of congenital agammaglobulinemia.

Other tests

Lung function studies are central to the monitoring of lung disease. They should be done annually in children who can perform the test (usually from 5 years of age).

Procedures

Endoscopy and colonoscopy can be used to assess the extent and progression of inflammatory bowel disease. Bronchoscopy can be helpful in diagnosing and tracking chronic lung disease and infections.

Agammaglobulinemia Bruton. Treatment

There is no cure for this disease. The introduction of immunoglobulin is the main method of controlling the disease. Typical doses of 400-600 mg/kg/month should be given every 3-4 weeks. Doses and intervals may be adjusted based on individual clinical responses. Therapy should begin at 10-12 weeks of age. Therapy with IgG should begin with a minimum level of 500-800 mg/dL. Therapy should begin at 10-12 weeks of age.

Ceftriaxone may be used to treat chronic infections, pneumonia, or sepsis. If possible, clinicians should obtain antibiotic susceptibility cultures, as many organisms are already showing resistance to many antibiotics. Strep infections, in particular, may require ceftriaxone, cefotaxime, or vancomycin.

Bronchodilators, steroid inhalers, and regular lung function tests (at least 3-4 times a year) may be a necessary part of therapy in addition to antibiotics.

Chronic dermatological manifestations of atopic dermatitis and eczema are controlled by daily moisturizing of the skin with special lotions and steroids.

Surgery

Surgery may be limited to severe acute infections. The most common procedures include those used to treat patients with recurrent otitis media and those with chronic sinusitis.

Agammaglobulinemia Bruton. Complications

Complications include chronic infections, enteroviral infections of the central nervous system, increased incidence of autoimmune diseases, and skin infections. Patients have an increased risk of developing lymphoma.

Agammaglobulinemia Bruton. Forecast

Most patients can survive until the end of their fourth decade of life. The prognosis is good as long as patients are diagnosed and treated early with regular intravenous gamma globulin therapy.

Serious enterovirus infections and chronic lung disease are often fatal in adulthood.

Bruton's disease is a rather rare phenomenon, but nevertheless occurring. This disease is based on a genetic predisposition, that is, with a lack of body production of antibodies that can resist viruses.

A little about pathology

This pathology is an immunodeficiency inherited and caused by mutational changes in the genes for encoding Bruton's tyrosine kinase or intracellular signal exchange. This disease was once correctly formulated by a scientist in the year 52 of the last century, and the gene itself was named after him.

Molecules are involved in maturation and energy exchange at the intercellular level. The gene was found on the X chromosome, encoding more than 500 amino acids necessary for the final formation of tyrosine kinase.

Mutational changes in the disease do not allow B-lymphocytes to develop and function in the future, the purpose of which is the production of antibodies and memory cells. A healthy person is distinguished by the fact that these cells develop into B-lymphocytes, while in sick people their number is small and they are less active.

Organs such as the spleen, adenoids, intestines, lymph nodes and tonsils in patients with this pathology have small size parameters or may be completely absent. Hypogammaglobulinemia - this pathology is caused by a lack of B-lymphocyte cells in relation to a decrease in the size and number of antibodies.

Symptoms of the disease

Infections that provoke this disease can begin their development at an early age and remain at the same level throughout life. Bruton's agammaglobulinemia is manifested in the body's vulnerability to viral diseases, including purulent inflammatory processes, hemophilia and Pseudomonas aeruginosa.

Skin lesions are provoked by group A streptococci and staphylococci. Manifestations on the epidermis can be in the form of an abscess, furuncle and cellulitis. Eczema resembles allergic skin rashes.

Other infectious diseases include manifestations such as bacterial diarrhea, meningitis and sepsis. Patients may be affected by autoimmune hereditary pathologies, arthritis and thrombocytopenia.

Regular exposure of the patient to infection can lead to meningoencephalitis or encephalitis, which is subsequently fatal. And also puffiness and skin rashes appear on the body in places of extension of the joints.

Symptoms by age

The representatives of the stronger sex can develop such diseases:

the last stage of otitis media;
pneumonia;
influenza B virus;
meningococci and staphylococci.

In children under the age of 12, due to this pathology, bacteriosis develops, enclosed in separate capsules. Infection received from external negative factors develops otitis media, pneumonia, sinusitis and influenza B virus. All of these received diseases are difficult to treat.

In adulthood, problems associated with skin rashes remain for a long time due to the constant supply of staphylococcal or streptococcal infections, and otitis media gradually develops into chronic sinusitis.

Both young children and people of any age can be affected by autoimmune diseases.

Data based on examination by specialists show that male babies have small parameters for weight and height, due to the fact that they cannot develop due to Bruton's disease. Lymph nodes or tonsils on examination may not be determined at all, or be extremely small.

The pathology itself can be detected only when the child feels worse, that is, he becomes ill with a viral disease and no medications, including antibiotics, can help. But the development of gangrene in the form of ulcers on the skin and the presence of cellulite on the lower extremities is also not excluded.

Clinical picture of the disease

After the birth of a child, the pathology does not manifest itself in anything, since the content of immunoglobulin is at a normal level. But at 3–5 months of life, sepsis or pyoderma may occur, which cannot be treated with antibiotics. Further, the disease affects the lungs, middle ear and gastrointestinal tract. Pathologies such as meningitis, osteomyelitis and pansinusitis are noted.

Diagnosis of pathology

Early detection of Bruton's disease will help to avoid its further development and death from infections and lung diseases. The very fact of the pathology is confirmed by the absence or very low level of B lymphocytes, while at the same time a high level of T lymphocytes.

All this is determined on the basis of molecular analysis, which can be done at the stage of pregnancy in a mother who carries such a gene. An immunoglobulin test showing less than 100 units indicates confirmation of this disease. Sometimes Bruton's disease is discovered after the age of 20, because a mutation has occurred in the protein.

Laboratory tests include:

Conducting measurements of quantitative indicators of immunoglobulin E and A, testing for antibodies, the latter being best measured after reaching 6 months during the period of decrease in maternal antibodies. If less than 100 units of these indicators are found, this means that Bruton's disease is present.
After determining a prohibitively low level of antibodies, it is necessary to confirm this detection of a value. If the protein located on the surface of B-lymphocytes is also below 100 units, but the value for the analysis of T-cell lymphocytes increases.
Next comes the analysis needed to determine susceptibility to vaccines, such as pneumococcal.

In this way, you can verify the presence of Bruton's disease.

Along with the main ongoing studies, the condition of the lungs should be constantly monitored, as a rule, this is performed for children aged 5 years and over.

Treatment of the disease

To maintain the vital functions of the body, therapy throughout life is necessary. As a rule, intravenous vaccination with immunoglobulin or native plasma taken from healthy donors is used.

When the pathology is recognized for the first time, substitution treatment is carried out to saturate to a normal level of immunoglobulin over 400 units. If at this time the patient does not have inflammatory and purulent processes, then you can continue to put this vaccine as a prophylaxis.

If there is a disease such as a purulent abscess, regardless of its location, treatment with antibiotics is required.

In the treatment of symptoms of the disease, washing of the nasal sinuses with disinfectants, vibration massage of the chest and postural drainage of the lungs are performed.

Pathology predictions

If Bruton's disease is detected in a person at an early age, before the onset of its more severe manifestation, then properly prescribed and timely therapy will help maintain normal life activity.

But, nevertheless, statistics confirm that many cases of the disease are detected late in the period of inflammatory processes, then this circumstance threatens the unfavorable further development of the pathology.

Preventive actions

This disease has a genetic origin, so any preventive measures are powerless here. In order to prevent the manifestation of pathology, couples should be checked and consulted by a specialist before the birth of a child. If the newborn has signs of this disease, then the following should be done:

carrying out therapeutic measures;
well-prescribed therapy;
vaccination with inactivated drugs.

Bruton's disease is a primary humoral immunodeficiency that has arisen due to mutations in a gene that is inherited, as a result of which the human body is more susceptible to various infectious diseases, since the body does not produce enough immune molecules, the so-called immunoglobulins, which are required to protect the body from bacteria.

American pediatrician Ogden Bruton first described the disease in 1952. It was a boy suffering from Bruton's disease who was ill with various infectious diseases. Somewhere since the age of 4, he had pneumonia about 14 times, was treated for otitis media, meningitis, and sepsis. The analysis did not reveal antibodies. A group of scientists in 1993 independently conducted an experiment, as a result of which it was proved that the X-linked chromosome arose as a result of a mutation in the gene for a non-receptor tyrosine kinase, later it became known as Bruton's tyrosine kinase.

The reasons

Agammaglobulinemia (Bruton's disease) is a rather rare disease that mainly affects men, in rare cases it can be a woman. It is provoked at the genetic level, this disease is constrained to the X chromosome, resulting in a blockage in the growth of perfectly healthy immune pre-B cells, the so-called B-lymphocytes. This is directly related to the occurrence of defect tyrosine kinase. It takes part in the transduction of maturation of B-lymphocytes. The gene with the defect is located at the limit of the Xq21 chromosome. In order for immunoglobulins to fully protect the body from a variety of viruses and bacteria, sufficient production of them in the blood is required. But due to this disease, the production of immunoglobulins slows down or stops altogether. As a rule, the disease manifests itself when the child is more than six months old and it has the character of a chronic and recurrent disease of the bronchopulmonary apparatus. Allergic reactions to drugs often occur.

People who are exposed to this disease have a very high risk of infection with bacteria such as: Haemophilus influenzae, streptococci, pneumococci. Very often, as a result of concomitant infections, the gastrointestinal tract, lungs, skin, upper respiratory tract, and joints are affected. There is a high probability that relatives of the patient may also be affected by this disease, since Bruton's disease is hereditary.

Symptoms

The disease can be accompanied by a number of the following symptoms: diseases of the upper respiratory tract, skin lesions, conjunctivitis (inflammation of the eyeball), bronchitis, pneumonia, etc. Most often, these symptoms are observed in children aged 4 years. It can also be noted in a number of symptoms of bronchiectasis - bronchial dilatation and asthma attacks, and for no reason. During the period of illness, patients do not have an increase in lymph nodes, they do not suffer from hyperplasia of the tonsils, adenoids. Agammaglobulinemia occurs due to a mutation of the X chromosome gene encoding Bruton's tyrosine kinase (tkB, Btk - Brutontyrosinekinase). TKB plays a very important role in the development and maturation of B-lymphocytes. Antibodies and B-lymphocytes cannot form without TKB, so boys may have very small tonsils and lymph nodes that do not develop. This disease is usually prone to recurrent purulent infections of the lungs, paranasal sinuses, skin with encapsulated bacteria (Streptococcus pneumoniae, Hemophilus influenzae), and there is also a high probability of damage to the central nervous system, due to vaccination with live oral polio vaccine, Echo and Coxsackie viruses. These infections usually occur as progressive dermatomyositis, which may or may not be accompanied by encephalitis.

Diagnostics

Diagnose by flow cytometry to measure the number of B-lymphocytes that circulate in the blood. Serum immunoelectrophoresis is performed, using nephelometry, the amount of immunoglobulins contained in the blood is measured.

Treatment

During treatment, the patient is administered intravenous immunoglobulin preparations 400 mg per 1 kg of body weight to strengthen and maintain the immune system as a whole, and antibiotics are also used, which inhibit and slow down the spread and development of various bacteria. Of particular importance is the timely conduct of antibiotic therapy, if the progression of the infectious process suddenly occurs, and with the replacement of antibiotics, it is desirable to treat bronchiectasis. With intravenous treatment, the well-being of patients suffering from agammaglobulinemia improves sufficiently. The prognosis for recovery will be favorable if adequate and appropriate treatment is prescribed in the early stages of the disease. But if treatment is not started on time, there is a high probability that severe concomitant diseases can lead to the death of the patient.

Hereditary hypogammaglobulinemia requires parenteral antimicrobial therapy. For best results, it should be carried out simultaneously with concomitant or replacement therapy. The duration of antibiotic treatment is approximately 10-14 days, but can increase up to 21 days. The most common antimicrobial drugs that are used in the treatment are cephalosporins, aminoglycosides, sulfonamides and penicillin antibiotics.

From the medical history

A case that was recorded in 1985. A male baby was born with a normal weight of 3500 g and a height of 53 cm, the birth was successful without deviations from the norm. The mother, being pregnant, suffered ARVI at 4 months. In the first month of life, the boy had conjunctivitis. After 1 year, the boy becomes a regular patient with a diagnosis of acute respiratory infections, bronchitis with a suffocating cough, with stable enterocolitis. At 2 years old, the child suffers pneumococcal meningitis. And he will face generalized edema at the age of 5 years, there is also increased shortness of breath, cyanosis. He has pain in his joints and in his heart. The liver and spleen were examined and their size increased by several times, the baby was urgently hospitalized. After a thorough examination in the laboratory, tests were taken, in which they found severe lymphocytopenia, as well as traces of immunoglobulins of all classes. Before hospitalization, antibiotic treatment was carried out to eliminate the focus of infections. In view of this disease, intravenous immunoglobulin was used, including antibiotic therapy. The patient's condition improved after appropriate treatment, there were almost no foci of infections left in the body. And a year after the illness, the patient was hospitalized again, but with bilateral conjunctivitis, as well as bronchopneumonia. Treatment was repeated with intravenous gamma globulin, simultaneously with antibiotic therapy. After the treatment, the patient was discharged with the following recommendations: continuous intake of gamma globulin under careful monitoring of blood levels. At the same time, the boy's parents are absolutely healthy.