FEATURE LABORATORY DIAGNOSTICS 029
HLA-Cw6 determination is particularly important in the differential diagnosis of chronic inflammatory skin diseases, since this variant is strongly associated with type 1 psoriasis vulgaris and guttate psoriasis, but only comparatively weakly associated with type 2 psoriasis vulgaris. Since type 1 psoriasis vulgaris has a more severe course than type 2, the presence of HLA-Cw6 indicates a more serious form of disease. An accurate diagnosis can help with decisions concerning therapy and preventative measures to be implemented.
HLA-B27 IN ANKYLOSING SPONDYLITIS Ankylosing spondylitis (Bechterew’s disease) is a chronic inflammatory disease of the axial skeleton, extremity joints and tendon insertions, which affects predominantly men between the ages of 15 and 30. It is not curable, and therapy focuses on reducing symptoms and managing pain. There is a clear relationship between ankylosing spondylitis and the tissue antigen HLA-B27. Around 90% of patients are carriers of HLA-B27, compared to 6-9% of the general population. However, only 3-6% of carriers actually develop the disease. HLA-B27 is also linked to a number of other conditions, including Reiter’s syndrome, inflammatory eye disorders, various forms of arthritis and chronic inflammatory bowel diseases. HLA-B27 determination is an important component in the diagnosis of ankylosing spondylitis and associated rheumatic diseases. Further, discrimination between different HLA-B27 subtypes is critical, since some HLA-B27 subtypes are associated with disease, while others are not. Thus, a thorough genetic analysis encompassing a comprehensive differentiation of subtypes is a prerequisite.
FACTOR V AND II MUTATIONS IN THROMBOPHILIA Thrombophilia is a increased tendency for blood coagulation. It can be fatal, with deep and superficial thrombosis and thromboembolism of the brain and coronary vessels the most frequent causes of death. The condition results from a combination of genetic and acquired factors. The latter include old age, long-term immobility, varicose veins, use of oral contraceptives and hormone replacement therapy. The most important genetic risk factor is the factor V Leiden
transglutaminase antibodies and anti-endomysium antibodies that can be now employed to diagnose CD without biopsy in these individuals. HLA- DQ2/DQ8 is also a useful exclusion parameter for clarifying ambiguous cases, especially in infants and persons already on a gluten-free diet, and for differentiating CD from other intestinal diseases.
HLA-CW6 IN PSORIASIS Psoriasis is a chronic inflammatory autoimmune disease, which manifests predominantly on the skin, but can also affect other organs such as joints, eyes and vascular system. It is one of the most common inflammatory skin diseases, and affected individuals often suffer stigmatisation and social exclusion. There is currently no cure, and treatment is based on the relief of symptoms and psychosocial therapy. There is a strong genetic component to psoriasis. Around 40% of
psoriasis cases are familial, with a concordance rate in identical twins of 62-70% and in non-identical twins of 21-23%. The most powerful genetic marker for this disease is the allele coding for the tissue antigen HLA-Cw6. Around 67% of psoriasis patients exhibit HLA-Cw6, compared to 10-20% of the general population. But not all predisposed persons develop psoriasis, as further triggers such as infections, drugs and extreme stress must also be present.
mutation. This is a point mutation in the factor V gene, which results in the exchange of one amino acid. The altered factor V cannot be sufficiently inactivated by activated protein C (APC) leading to an increased thrombotic tendency (APC resistance). Around 3-7% of the population has the heterozygous genotype, while homozygous mutations are relatively rare (approximately 0.2%). The mutation 20210G>A in the factor II (prothrombin) gene is also a major genetic risk factor. This mutation, located in the promoter region of the gene, leads to an increase in the prothrombin level in the plasma. Around 1-3% of the population is a heterozygous carrier, and less than 0.1% has the homozygous mutation. If both the factor V and factor II mutations are present, the risk of venous thrombosis is increased twenty fold, and this combination is frequently found in thrombophilia patients. Analysis of factor V and II mutations is indicated in patients with thrombosis or embolism, particularly at a young age, at an atypical location or of unknown origin. Genetic clarification is also recommended in cases of recurring miscarriages, APC resistance, or protein C or S deficiency. Moreover, a genetic analysis is advised before giving oral contraceptives or hormone replacement therapy to women considered at risk of thrombosis or embolism.
INNOVATIVE MICROARRAY TECHNOLOGY Genetic disease factors can be analysed using microarray technology, such as the EUROArray system — a state-of-the-art molecular
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