Titer of antibodies to nuclear antigens( antinuclear factor) in serum
In healthy people, the titre of AT to nuclear arteries in serum 1: 40-1: 80( clinically significant titer -> 1: 160 using indirect immunofluorescence method, using screening methods - below 1:50).
Antinuclear factor - AT to the whole nucleus. This is a heterogeneous group of autoantibodies that react with different components of the nucleus. Determination of AT for nuclear arteries in blood serum is a test for systemic diseases of connective tissue. Screening for the presence of antinuclear antibodies in the blood 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 distribution of the label) is the least specific, possibly with SLE, drug lupus syndrome and other autoimmune diseases, and in the elderly. 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 Ar, against which antinuclear ATs are directed, is deoxyribonucleoprotein.
■ Homogeneous or peripheral staining is observed when the AT is dominated by the double-stranded DNA in the test serum. This type of staining is most often detected with SLE.
■ Spotted or speckled staining is due to AT to the extracted nuclear Ag and is usually observed with mixed connective tissue disease, Sjogren's syndrome, drug lupus syndrome.
■ Nucleolar( nucleolar) staining( label distribution near the nucleoli) is due to AT to ribonucleoprotein. 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 AT to centromere( a specialized domain of chromosomes) and is characteristic of CREST-syndrome and other autoimmune rheumatic diseases.
The main objective of the study for antinuclear AT is the detection of SLE, since in this disease they appear in the serum of 95% of patients within 3 months after its onset.
The determination of AT to nuclear Ag 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, with SLE - up to 1: 1000 and above. With SLE, the antinuclear factor detection test has a high sensitivity( 89%), but a moderate specificity( 78%) compared to the AT test for native DNA( sensitivity 38%, specificity 98%).AT to nuclear Ar are highly specific for SLE.Preservation of a high level of AT for a long time is an unfavorable sign. Reducing titre heralds remission or( sometimes) death.
With scleroderma, the frequency of detection of AT to nuclear Ar is 60-80%, but their titer is lower than with SLE.Between the titre of the antinuclear factor in the blood and the severity of the disease, the relationship is not traced. In rheumatoid arthritis SCR-like forms of flow are often isolated, therefore, AT is often often identified with nuclear arteries. In the case of dermatomyositis of AT to nuclear arteries, blood is 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 antinucleary factor is detected in 50% of patients.
In addition to rheumatic diseases, AT to nuclear Ag in the blood is detected in chronic active hepatitis( in 30-50% of cases), and
Fig. Algorithm for diagnosis of rheumatic diseases [Lehman C. A., 1998]
Fig. Algorithm for the diagnosis of rheumatic diseases [Lehman C. A., 1998]
their titer sometimes reaches 1: 1000.Autoantibodies to nuclear Ag 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, CRF, thrombocytopenia, lymphoproliferative diseases, myasthenia and thymomas.
Almost 10% of cases of antinuclear factor are 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, which differs in its simplicity 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, p-adrenoblockers, hydralazine, penicillamine, nitrofurantoinand others, due to the ability of these drugs to cause interference during the study.