Antibodies to nucleic antigens (antinuclear factor) in blood

In healthy people, the titer of antibodies to nuclear antigens in the blood serum is 1:40-1:80 (clinically significant titer is ≥1:160 when using the indirect immunofluorescence method; when using screening methods - below 1:50).

Antinuclear factor - antibodies to the whole nucleus. This is a heterogeneous group of autoantibodies that react with various components of the nucleus. Determination of antibodies to nuclear antigens in the blood serum is a test for systemic connective tissue diseases. Screening for the presence of antinuclear antibodies in the blood serum is carried out by radioimmunoassay (RIA), complement fixation reaction (CFR) or ELISA.

Positive screening results should be confirmed by the indirect immunofluorescence method. Preparations prepared from a suspension of cells with large nuclei [from human epithelial cells of the HEp-2 line - laryngeal cancer cells, or mouse liver sections] are used as a cellular substrate. The type of staining (the nature of the distribution of the fluorescent label in the cells) is different for different diseases and determines the direction of further determination of the specificity of antinuclear antibodies.

• Diffuse staining (uniform distribution of the label) is the least specific, possible in systemic lupus erythematosus, drug-induced lupus syndrome and other autoimmune diseases, as well as in elderly individuals. In case of diffuse staining of cells, the reaction must be repeated with a higher dilution of the blood serum being tested. If the staining type remains the same, it is most likely that the antigen against which the antinuclear antibodies are directed is deoxyribonucleoprotein.
• Homogeneous or peripheral staining is observed when antibodies to double-stranded DNA predominate in the serum being examined. This type of staining is most often found in systemic lupus erythematosus.
• Spotted or mottled staining is due to antibodies to extractable nuclear antigens and is usually seen in mixed connective tissue disease, Sjögren's syndrome, and drug-induced lupus syndrome.
• Nucleolar staining (label distribution in the nucleoli) is caused by antibodies to ribonucleoprotein (see below). This type of staining is typical for systemic scleroderma, and is occasionally possible in other autoimmune diseases.
• Centromeric or discrete speckled staining is caused by antibodies to the centromere (a specialized domain of chromosomes) and is characteristic of CREST syndrome and other autoimmune rheumatic diseases.

The main goal of the study for antinuclear antibodies is to identify systemic lupus erythematosus, since in this disease they appear in the blood serum of 95% of patients within 3 months after its onset.

Determination of antibodies to nuclear antigens is of great importance for diagnostics of collagenoses. In nodular polyarteritis, the titer (using screening methods) can increase to 1:100, in dermatomyositis - to 1:500, in systemic lupus erythematosus - to 1:1000 and higher. In systemic lupus erythematosus, the test for detection of antinuclear factor has a high degree of sensitivity (89%), but moderate specificity (78%) compared with the test for detection of antibodies to native DNA (sensitivity 38%, specificity 98%). Antibodies to nuclear antigens are highly specific for systemic lupus erythematosus. Maintaining a high level of antibodies for a long time is an unfavorable sign. A decrease in the titer foretells remission or (sometimes) a fatal outcome.

In scleroderma, the frequency of detection of antibodies to nuclear antigens is 60-80%, but their titer is lower than in systemic lupus erythematosus. There is no relationship between the titer of antinuclear factor in the blood and the severity of the disease. In rheumatoid arthritis, SLE-like forms of the disease are often distinguished, so antibodies to nuclear antigens are detected quite often. In dermatomyositis, antibodies to nuclear antigens in the blood are detected in 20-60% of cases (titer up to 1:500), in nodular polyarteritis - in 17% (1:100), in Sjögren's disease - in 56% when combined with arthritis and 88% of cases in Gougerot-Sjögren's syndrome. In discoid lupus erythematosus, antinuclear factor is detected in 50% of patients.

In addition to rheumatic diseases, antibodies to nuclear antigens in the blood are detected in chronic active hepatitis (in 30-50% of cases), and their titer sometimes reaches 1:1000. Autoantibodies to nuclear antigens can appear in the blood in infectious mononucleosis, acute and chronic leukemia, acquired hemolytic anemia, Waldenström's disease, liver cirrhosis, biliary cirrhosis, hepatitis, malaria, leprosy, chronic renal failure, thrombocytopenia, lymphoproliferative diseases, myasthenia and thymomas.

In almost 10% of cases, antinuclear factor is detected in healthy people, but in low titers (no more than 1:50).

In recent years, an enzyme immunoassay method for determining antinuclear antibodies of various spectra has been developed, which is easy to perform and is gradually replacing the immunofluorescence method.

A number of drugs can lead to a false-positive increase in the titer of antinuclear antibodies: aminosalicylates, carbamazepine, isoniazid, methyldopa, procainamide, iodides, oral contraceptives, tetracyclines, thiazide diuretics, sulfonamides, nifedipine, β-blockers, hydralazine, penicillamine, nitrofurantoin, etc., due to the ability of these drugs to cause interference during the study.

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