IMUNOGENETICS

It is estimated that about 0.5% of the global population suffers from the disease, and the frequency of this allele in the Caucasian population is 7-9%. The HLA-B27 allele has been found in 90-95% of all patients with Bechterew's disease.

The first symptoms of the disease most often appear between the ages of 18 and 30. The disease gradually causes damage to or ossification of joint capsules and ligaments, leading to limited joint mobility. Clinically, it is manifested by pain and stiffness initially in the sacroiliac joint and lumbar spine, especially when the body is in the same position for a long time. Chest pain may also occur, especially with deep breathing, and chronic and severe fatigue is common.

Other health problems may also indicate the presence of the disease, e.g., psoriatic skin changes and inflammation of the iris and ciliary body (in 40% of patients), idiopathic intestinal inflammation (Crohn's disease and ulcerative colitis), autoimmune heart and aortic disease, and antibody deposition (especially IgA) in the kidneys. The cause of Bechterew's disease is still not completely clear, but the relationship of the disease with the HLA-B27 antigen has long been known. The presence of the HLA-B27 allele alone does not cause Bechterew's disease, but other factors are needed to cause it, the nature of which we do not yet know.

HLA-B27 antigen carriers are about 300 times more likely to develop the disease than individuals without the antigen. The indication for genetic testing is a differential diagnostic consideration associated with clinical symptoms (unilateral anterior eye chamber uveitis, back pain, positive family history, skin manifestations and associated rheumatic diseases). Molecular genetic detection of the HLA-B27 allele is indicated especially in patients with an equivocal flow cytometry result (the result is marked as reactive, not positive).

Gene, specification: HLA-B27 (Human Leucocyte Antigen) allele

Type of material to be examined: blood, buccal swab

Indicating specialists: medical genetics, rheumatology, allergology and clinical immunology

The disease affects the lining of the small intestine. However, the clinical picture varies from gastrointestinal manifestations to extraintestinal (Duhring's dermatitis) and to an asymptomatic form.

Celiac disease can manifest at any age, often after mental or physical stress - for women it can be childbirth, for both sexes any surgery, usually between 30 and 40 years. Until then, the individual may have unexplained anaemia caused by impaired absorption of important nutrients and iron. In children, gastrointestinal symptoms, failure to thrive to failure to grow and iron deficiency anaemia predominate.

The basis of diagnosis is the detection of antibodies against tissue transglutaminase type 2 (anti-TG2), which plays a role in the pathogenesis of celiac disease. However, at the time of the examination, the patient must consume a diet with sufficient gluten (at least 15 g/day). The detection of the risk genotype cannot be interpreted as a confirmation of the celiac disease diagnosis, as about 35-40% of the Caucasian population is HLA-DQ positive, but only about 1% develop celiac disease during their lifetime (low positive predictive value of the test).

Final confirmation of the diagnosis in adults is possible only during enterobiopsy. Therefore, genetic testing is used to exclude celiac disease in the differential diagnostic considerations, as the negativity of HLA-DQ2 and HLA-DQ8 virtually excludes the diagnosis of celiac disease (high sensitivity of the test). HLA-DQ typing is recommended in patients with an unclear diagnosis, in patients with a positive family history of celiac disease, and in patients with diseases that have an association with celiac disease. Diseases clearly associated with celiac disease in childhood include type 1 diabetes mellitus, juvenile idiopathic arthritis, IgA nephropathy, serum IgA deficiency, autoimmune thyroiditis, autoimmune hepatitis, Down syndrome, Turner syndrome and Williams syndrome.

The diagnosis without enterobiopsy is made only by a paediatric gastroenterologist based on meeting all the criteria. In adult patients with a strong clinical suspicion of celiac disease and high levels of specific antibodies, the use of genetic HLA-DQ typing can be considered to confirm the diagnosis of celiac disease without the need for invasive biopsy.

Celiac disease is an incurable disease whose only successful treatment is a strict gluten-free diet. The main genetic factors associated with celiac disease include Major Histocompatibility Complex (MHC) class II molecules, which are essential for the body's immune response. Carriers of HLA-DQ2 or HLA-DQ8 haplotypes have an increased risk of developing celiac disease, with approximately 95% of celiac patients carrying the HLA-DQ2 haplotype and the remaining 5% the HLA-DQ8 haplotype.

Gene, specification: HLA alleles (Human Leucocyte Antigen) DQA1, DQB1 (haplotypes DQ2cis, DQ2trans, DQ8

Type of material to be examined: blood, buccal swab

Indicating specialists: medical genetics, gastroenterology and hepatology, paediatrics (only in children with antigliadin antibodies 10 times above the norm), allergology and clinical immunology

Intolerance can also arise secondary to another disease, e.g., celiac disease. Lactose intolerance presents clinically with a variety of intestinal symptoms such as bloating, abdominal colic and diarrhoea after ingestion of lactose-containing foods. It is estimated that up to 36% of the Caucasian population is lactose intolerant to varying degrees. Intolerance manifests itself at any age and both men and women are affected equally. The lactase enzyme (phlorizin hydrolase) is encoded by the LCT gene, which is located on chromosome 2q21. Single nucleotide polymorphisms C/T-13910 and G/A-22018, which are 14 and 22 kb upstream of the LCT gene, are associated with reduced enzyme activity and reduce gene transcription and thus enzyme levels. We are talking about lactase nonpersistence - lactose intolerance. If these polymorphisms are not proven or only one is proven, we speak of lactase persistence - normal lactase activity.

Gene, specification:  LCT gene, polymorphisms C/T-13910, G/A-22018

Type of material to be examined: blood, buccal swab

Indicating specialists: medical genetics, gastroenterology and hepatology, allergology and clinical immunology

The incidence of this disease is not precisely known, but is reported to be in the range of 1 : 12,000 and 1 : 58,000 The disease is caused by a deficiency of the enzyme aldolase B. Clinical signs appear shortly after the infant is given milk replacer and fruit containing sucrose (which is broken down into fructose and glucose) or honey.

Symptoms begin non-specifically with vomiting and diarrhoea with episodes of hypoglycaemia. Prolonged intake of fructose can lead to severe liver and kidney damage, which can result in death (especially in young children). The treatment is complete elimination of fructose from the diet, along with vitamin C supplementation, as a fructose-free diet requires elimination of most natural sources of vitamin C. Sorbitol must also be eliminated from the diet.

The ALDOB gene for aldolase B is localized on chromosome 9. More than three dozen mutations have been described in this gene, with the most common mutations in the European population being A149P, A174D and N334K, which account for more than 85% of all HFI mutant alleles.

Gene, specification: ALDOB (del4E4, p.A149P, p.A174D, p.N334K)

Type of material to be examined: blood, buccal swab

Indicating specialists: medical genetics, gastroenterology and hepatology, paediatrics, allergology and clinical immunology

Diamine oxidase is an enzyme highly expressed in the intestine that breaks down histamine in the body. Histamine intolerance means an elevated level of histamine and manifests itself in a variety of symptoms, including flatulence, cramps, diarrhoea, difficulty breathing, headaches, hypotension, arrhythmias, and allergy-like symptoms such as rhinitis, urticaria, pruritus and others. In the differential diagnosis of the above-mentioned disorders, it is recommended to test the activity of the DAO enzyme in the blood and perform genetic testing for hereditary predisposition. The genetic test has the advantage of distinguishing between primary (genetic) and secondary (probably reversible) forms of intolerance.

The treatment of histamine intolerance is an individually adjusted low-histamine diet (the patient can tolerate a certain amount of histamine in the diet) or complete elimination of histamine from the diet. The DAO enzyme is encoded by the AOC1 gene, in which more than 50 mutations have been described. In the Caucasian population, four mutations occur most frequently: c.-691G>T, c.-594A>T, c.47C>T and c.995C>T, which alter the functionality of the enzyme.

Gene, specification: AOC1 gene (c.-691G>T, c.-594A>T, c.47C>T, c.995C>T)

Type of material to be examined: blood, buccal swab

Indicating specialists: medical genetics, gastroenterology and hepatology, internal medicine, allergy and clinical immunology, paediatrics, GP for children and adolescents, general practical medicine