Antibodies to nuclear antigens (antinuclear factor) in the blood

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

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

Positive screening results should be confirmed by indirect immunofluorescence. As a cellular substrate, preparations prepared from a suspension of cells with large nuclei [from human cells of the human epithelial cells (larynx cells or murine liver slices) are used. The type of staining (the character of distribution of the fluorescent label in the cells) for different diseases is not the same and determines the direction of further establishment of the specificity of antinuclear antibodies.

• Diffuse staining (uniform label distribution) is the least specific, possibly with systemic lupus erythematosus, drug lupus syndrome and other autoimmune diseases, as well as in elderly people. With diffuse staining of cells, the reaction must be repeated with a large dilution of the blood serum under study. If the type of staining remains the same, it is most likely that the antigen against which antinuclear antibodies are directed is deoxyribonucleoprotein.
• Homogeneous or peripheral staining is observed when antibodies to double-stranded DNA predominate in the test serum. This type of staining is most often found in systemic lupus erythematosus.
• Spotted or mottled staining is due to antibodies to extracted nuclear antigens and is usually observed with mixed connective tissue disease, Sjogren's syndrome, drug lupus syndrome.
• The nucleolar (nucleolar) staining (label distribution in the nucleolus region) is due to antibodies to the ribonucleoprotein (see below). This type of staining is characteristic of systemic scleroderma, and occasionally it is possible with other autoimmune diseases.
• Centromeric or discrete speckled staining is due to antibodies to the centromere (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 the detection of systemic lupus erythematosus, since in this disease they appear in the blood serum of 95% of patients within 3 months after its onset.

The determination of antibodies to nuclear antigens is of great importance for the diagnosis of collagenosis. With nodular polyarteritis, the titer (using screening methods) can increase to 1: 100, with dermatomyositis - up to 1: 500, in systemic lupus erythematosus - up to 1: 1000 and above. In systemic lupus erythematosus, the antinuclear factor test has a high sensitivity (89%), but moderate specificity (78%) compared to the test for antibodies against native DNA (sensitivity 38%, specificity 98%). Antibodies to nuclear antigens are highly specific for systemic lupus erythematosus. Preservation of a high level of antibodies for a long time is an unfavorable sign. A decrease in titre heralds a remission or (sometimes) a fatal outcome.

With scleroderma, the detection rate of antibodies to nuclear antigens is 60-80%, but their titer is lower than with systemic lupus erythematosus. Between the titre of the antinuclear factor in the blood and the severity of the disease, the relationship is not traced. With rheumatoid arthritis SCR-like forms of flow are often isolated, therefore antibodies to nuclear antigens are often detected. With dermatomyositis antibodies to nuclear antigens in the blood are detected in 20-60% of cases (titer up to 1: 500), in case of nodular polyarteritis - in 17% (1: 100), in Sjogren's disease - in 56% when combined with arthritis and 88% cases with Guzero-Sjogren's syndrome. In discoid lupus erythematosus, the 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 kidney failure, thrombocytopenia, lymphoproliferative diseases, myasthenia and thymomas.

Almost in 10% of cases antinuclear factor is found in healthy people, but in low titer (no more than 1:50).

In recent years, an enzyme-linked immunosorbent assay for the detection of antinuclear antibodies of various spectra has been developed that is easy to perform and gradually displaces 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-adrenoblockers, hydralazine, penicillamine, nitrofurantoin, etc., due to the ability of these drugs to cause interference during the study.

[1], [2], [3], [4],