Agammaglobulinemiya – it is hereditary the caused disease at which heavy primary immunodeficiency (defect of immune protection of an organism) with the expressed decrease in level of gamma globulins develops in blood. The disease usually in the first months and years of life of the child when repeated bacterial infections begin to develop is shown: otitis, sinusitis, pneumonia, piodermiya, meningitis, sepsis. At inspection in peripheral blood and marrow there are practically no serumal immunoglobulins and B-cages. Treatment of an agammaglobulinemiya consists in lifelong replacement therapy.
Agammaglobulinemiya (hereditary gipogammaglobulinemiya, Bruton's disease) – the congenital defect of humoral immunity caused by mutations in a genome of cages that results in insufficiency of synthesis of B-lymphocytes. Formation of immunoglobulins of all classes is as a result broken, and their content in blood sharply decreases up to total absence, primary immunodeficiency develops. Low reactivity of immune system leads to development of a serious repeated pyoinflammatory illness of ENT organs, bronchial tubes and lungs, digestive tract and brain covers. Bruton's disease occurs only at boys and is observed approximately at 1-5 people from one million newborns, irrespective of race and ethnic group.
The X-linked form of a hereditary agammaglobulinemiya arises owing to damage of one of X-chromosome genes (it is located on Xq21.3-22.2). This gene is responsible for synthesis of the enzyme of a tyrosinekinase participating in process of education and a differentiation of B-cages. As a result of mutations of this gene and blocking of synthesis of a brutonovsky tyrosinekinase formation of humoral immunity is broken. At an agammaglobulinemiya young forms ( - B - cages) are present at marrow, and their further differentiation and receipt to the blood course is broken. Respectively, development of all classes of immunoglobulins is practically not made, and the organism of the child becomes defenseless at penetration of pathogenic bacteria (most often it is streptococci, staphylococcus and a sinegnoyny stick).
The similar mechanism of violations is noted also in a case with other form of a hereditary agammoglobulinemiya - linked to the X-chromosome and insufficiency of hormone of growth. Autosomno-retsessivnaya the form develops as a result of a mutation of several genes (µ-heavy chains, a gene λ5/14.1, a gene of adaptor protein and a gene of the alarm molecule IGA).
Allocate three forms of a hereditary agammaglobulinemiya:
- linked to the X-chromosome (85% of all cases of congenital gipogammaglobulinemiya, are ill only boys)
- autosomno-recessive sporadic the Swiss type (occurs at boys and girls)
- the agammaglobulinemiya linked to the X-chromosome and insufficiency of hormone of growth (occurs extremely seldom and only at boys)
The reduced reactivity of humoral immunity at agammaglobulinemiya leads to development of repeated pyoinflammatory diseases on the first year of life of the child (as a rule, after the breastfeeding termination – in 6-8 months). At the same time protective antibodies from mother do not come to the child's organism any more, and the immunoglobulins – are not produced. To 3-4 summer age inflammatory processes pass into a chronic form with tendency to generalization. The purulent infection at an agammaglobulinemiya can affect various bodies and systems.
From ENT organs purulent antritises, etmoidita, otitises are frequent, and purulent otitis develops on the first year of life of the child more often, and sinusitis – in 3-5 years. From diseases of bronchopulmonary system repeated bronchitis, pneumonia, lung abscesses are observed.
Often damage of digestive tract meets the persistent diarrhea (ponosa) caused by a chronic infectious enterokolit (the main activators – campylobacters, lyambliya, a rotavirus). On integuments impetigo, microbic eczema, recuring , abscesses and phlegmons is found.
Damage of eyes (purulent conjunctivitis), oral cavities (ulcer stomatitises, gingivita), bone and muscular system is frequent (osteomiyelita, purulent arthritises). In general the clinical picture of an agammaglobulinemiya is characterized by a combination of the general symptoms observed at a purulent infection (high temperature of a body, a fever, muscle pains and a headache, the general weakness, a sleep disorder and appetite etc.) and signs of defeat of concrete body (cough, short wind, the difficulty of nasal breath purulent separated diarrhea, etc.).
Any infectious and somatic disease at the patient with an immunodeficiency proceeds hard, is long and is followed by complications. The heavy current of an agammoglobulinemiya can be complicated by development of meningitis, viral encephalomyelitis, vaccine-challenged paralytic poliomyelitis, sepsis. Against the background of a disease the probability of development of autoimmune and oncological diseases is increased. Death of patients often occurs from infectious and toxic shock.
At clinical examination of the patient by the doctor by the allergist-immunologist the signs of pyoinflammatory defeat of this or that body (fabric) and symptoms confirming the reduced reactivity of immune system come to light: hypoplasia of almonds, reduction of peripheral lymph nodes. Also lag signs are expressed in physical development of the child.
Laboratory blood test reveals the expressed decrease in level of immunoglobulins in an immunogramma (IgA and IgM < 20 / – , IgG < 200 / – ) . B- ( 1%), . , T- . () .
Differential diagnostics of a hereditary agammaglobulinemiya is carried out with other primary and secondary immunodeficiency (genetic disorders, HIV and a Cytomegaloviral infection, a congenital rubella and toxoplasmosis, malignant new growths and system violations, an immunodeficiency owing to intoxication medicines, etc.).
Treatment of an agammaglobulinemiya
Lifelong replacement therapy by antitelosoderzhashchy medicines is necessary. Introduction of intravenous immunoglobulin is usually used, and at its absence – native plasma from healthy constant donors. At for the first time the established diagnosis of an agammaglobulinemiya replaceable treatment is carried out in the saturation mode before achievement of level of IgG immunoglobulin higher than 400 mg/dl then in the absence of active pyoinflammatory process in bodies and fabrics it is possible to pass to the supporting therapy with introduction of preventive doses of the medicines containing immunoglobulins.
Any episode of a bacterial purulent infection, irrespective of localization of inflammatory process, demands performing adequate antibacterial therapy which is carried out along with replaceable treatment. More often at an agammaglobulinemiya antibacterial means from group of tsefalosporin, aminoglycosides, macroleads, and also antibiotics of a penicillinic row are used. Treatment duration at the same time several times exceeds standard at this disease.
Symptomatic treatment is carried out taking into account concrete defeat of this or that body (washing of okolonosovy bosoms of a nose by antiseptics, performance of vibration massage of a thorax and a posturalny drainage at bronchitis and pneumonia etc.).
If the agammaglobulinemiya is found at early age before heavy complications, and replacement therapy adequate to a condition of the patient is begun in due time, preservation of a normal way of life for many years is possible. However in most cases diagnosis of inherited disorders of humoral immunity is performed too late when irreversible chronic pyoinflammatory diseases of bodies and systems of an organism already developed. In this case the forecast at an agammaglobulinemiya adverse.