Systemic lupus erythematosus. Laboratory research. Tests for lupus

Laboratory research

Thrombocytopenia is usually detected in patients with APS. Very rarely, autoimmune thrombocytopenia develops associated with the synthesis of AT to platelets.
. An increase in CRP is unusual; noted in most cases in the presence of concomitant infection. Moderate increase in CRP concentration (<10 мг/мл) ассоциируется с атеросклеротическим поражением сосудов.

General urine analysis
Proteinuria, hematuria, leukocyturia are detected, the severity of which depends on the clinical and morphological variant of lupus nephritis.

Biochemical studies
Changes in biochemical parameters are nonspecific and depend on the predominant damage to internal organs during different periods of the disease. Immunological studies
. Antinuclear factor (ANF) is a heterogeneous population of autoantibodies that react with various components of the cell nucleus. ANF ​​is detected in 95% of patients with SLE (usually in high titer); its absence in the vast majority of cases argues against the diagnosis of SLE.

Antinuclear AT. ATs to double-stranded (native) DNA (anti-DNA) are relatively specific for SLE; detected in 50-90% of patients ♦ AT to histones, more typical for drug-induced lupus. AT to 5m antigen (anti-Sm) are highly specific for SLE, but they are detected only in 10-30% of patients; AT to small nuclear ribonucleoproteins is more often detected in patients with manifestations of mixed connective tissue disease ♦ AT to Ro/SS-A antigen (anti-Ro/SSA) is associated with lymphopenia, thrombocytopenia, photodermatitis, pulmonary fibrosis, Sjögren's syndrome. AT to La/SS-B antigen (anti-La/SSB) is often found together with anti-Ro.

APL, false-positive Wasserman reaction, lupus anticoagulant and AT to cardiolipin are laboratory markers of APS.

Other laboratory abnormalities
In many patients, so-called lupus cells are detected - LE (ot lupus erythematosus) cells (leukocytes that have phagocytosed nuclear material), circulating immune complexes, RF, but the clinical significance of these laboratory abnormalities is small. In patients with lupus nephritis, a decrease in the total hemolytic activity of complement (CH50) and its individual components (C3 and C4), which correlates with the activity of nephritis (especially the C3 component), is observed.

Diagnostics

American Rheumatology Association Criteria

3. Photosensitivity: A skin rash that occurs as a result of an unusual reaction to sunlight.
4. Oral ulcers: ulceration of the oral cavity or nasopharynx; usually painless.

5. Arthritis: non-erosive arthritis affecting 2 or more peripheral joints, manifested by tenderness, swelling and effusion.
6. Serositis: pleurisy (pleural pain, or pleural friction rub, or the presence of pleural effusion) or pericarditis (confirmed by echocardiography or auscultation of a pericardial friction rub).

7. Kidney damage: persistent proteinuria >0.5 g/day or cylinder (erythrocyte, hemoglobin, granular or mixed).
8. Damage to the central nervous system: convulsions or psychosis (in the absence of taking drugs or metabolic disorders).

9. Hematological disorders: hemolytic anemia with reticulocytosis, or leukopenia<4,0х109/л (зарегистрированная 2 и более раза), или тромбоцитопения <100х109/л (в отсутствие приёма ЛС).

10. Immunological disorders ♦ anti-DNA or ♦ anti-Sm or ♦ aPL: -increased level of IgG or IgM (AT to cardiolipin); - positive test for lupus anticoagulant using standard methods; - false-positive Wasserman reaction for at least 6 months with a confirmed absence of syphilis using the Treponema pallidum immobilization test and the fluorescent adsorption test of treponemal AT.
11. ANF: increase in ANF titers (in the absence of taking drugs that cause lupus-like syndrome). The diagnosis of SLE is made when 4 or more of the 11 criteria listed above are found.

Diagnostic criteria for APS

II. Laboratory criteria
1. AT to cardiolipin (IgG and/or IgM) in the blood in medium or high titers in 2 or more studies with an interval of at least 6 weeks.
2. Plasma lupus anticoagulant in 2 or more studies at least 6 weeks apart, determined as follows:
. prolongation of plasma clotting time in phospholipid-dependent coagulation tests;
. lack of correction for prolongation of clotting time of screening tests in tests of mixing with donor plasma;
. shortening or correction of prolongation of the clotting time of screening tests when adding phospholipids;
. exclusion of other coagulopathies. A specific APS is diagnosed based on the presence of one clinical and one laboratory criterion.

If SLE is suspected, the following studies should be performed:
. general blood test with determination of ESR and counting the content of leukocytes (with leukocyte formula) and platelets. immunological blood test with determination of ANF. general urine analysis. chest x-ray
. ECG, echocardiography.

Systemic lupus erythematosus

Systemic lupus erythematosus is an autoimmune disease characterized by damage to the skin, musculoskeletal system, heart, kidneys and other internal organs.

Normally, cells of the immune system detect and destroy various foreign objects in the body (for example, infectious agents). In autoimmune processes, the immune system aggressively attacks the body's own cells and tissues, causing their inflammation and destruction.

The exact causes of the development of this disease are unknown, although researchers have identified some risk factors: genetic predisposition, exposure to certain infections (for example, Epstein-Barr virus), environmental factors (for example, exposure to sunlight, smoking).

Symptoms of systemic lupus erythematosus are varied. The disease may have an acute onset or progress slowly with mild clinical manifestations. The most common and characteristic symptom is damage to the skin and mucous membranes. In this case, red spots form on the face in the area of ​​the nose and cheeks, shaped like a butterfly.

Along with the skin, joints, kidneys, lungs, heart, and nervous system can be involved in the pathological process with the development of corresponding symptoms.

The prognosis depends on the severity of systemic lupus erythematosus. In some cases, during treatment it is possible to achieve long-term remissions (periods of complete absence of symptoms of the disease). Ten-year survival rate in developed countries is about 90%.

Synonyms Russian

Libman-Sachs disease.

English synonyms

Systemic Lupus Erythematosus, Libman-Sacks Disease.

Symptoms

• Increased body temperature;
• general weakness, fatigue;
• pain, swelling, limited mobility in joints;
• erythema (intense redness of the skin) in the nose and cheeks;
• erythematous rashes that may be slightly raised above the surface of the skin (lesions on the skin may appear or enlarge when exposed to sunlight);
• ulceration of the mucous membrane of the nasal cavity, mouth;
• hair loss;
• chest pain;
• dyspnea;
• paleness, coldness, feeling of numbness in the fingers and toes in the cold;
• disturbance of consciousness;
• memory loss;
• convulsions.

General information about the disease

Systemic lupus erythematosus is an autoimmune disease characterized by damage to various internal organs. It is based on autoimmune mechanisms. Cells of the immune system begin to destroy body structures, mistaking them for foreign objects. Complexes of immune cells (antibodies) and antigens (body cells) are formed in the blood, which spread throughout the body, causing inflammation in the affected organs. The vessels of the microvasculature (microscopic blood vessels: arterioles, venules, capillaries) are exposed to the aggressive effects of the immune system.

The exact causes of the disease are unknown. There are a number of factors that contribute to the development of systemic lupus erythematosus.

• Genetic predisposition. According to researchers, in the case of maternal disease, the risk of developing systemic lupus erythematosus in a girl child is 1:40, and in a boy child – 1:250.
• Infectious agents (for example, Epstein-Barr virus) can provoke autoimmune reactions that occur in systemic lupus erythematosus.
• Medicines (for example, some anticonvulsants, antihypertensives) can cause manifestations of systemic lupus erythematosus. As a rule, symptoms disappear after discontinuation of drugs.
• Exposure to sunlight in individuals predisposed to SLE may trigger the development of the disease.
• Hormonal changes in women. Scientists have found that the administration of estrogens during the postmenopausal period may increase the risk of SLE.

The most common syndrome with systemic lupus erythematosus is damage to the skin and mucous membranes. On the face in the area of ​​the nose and cheeks, erythema (intense redness formed as a result of the inflammatory process in the blood vessels) forms in the shape of a butterfly. In other areas of the body, erythematous spots may appear that are slightly raised above the surface of the skin. Ulcerations are found on the mucous membranes. Damage to small blood vessels causes trophic (caused by impaired tissue nutrition) changes in the skin. The consequence of this is brittle nails and hair loss.

From the musculoskeletal system, joint pain and manifestations of arthritis occur. Deformities in the affected joints rarely develop.

Involvement of the lungs in the pathological process can lead to pleurisy (inflammation of the membrane lining the chest cavity from the inside and the lungs from the outside), inflammation of the pulmonary vessels, the formation of blood clots in the pulmonary vessels, and pulmonary hemorrhages.

Sometimes myocarditis (inflammation of the heart muscle), endocarditis (inflammation of the inner lining of the heart involving the valve apparatus) develops. Vasculitis of the coronary arteries is also a serious complication.

Kidney damage can occur at any stage of the disease. The activity of the pathological process varies from asymptomatic to severe, rapidly progressive forms of glomerulonephritis (inflammation of the renal glomeruli), which lead to renal failure.

Foci of lesions form in the nervous system as a result of the involvement of its various parts in the pathological process. This is accompanied by headaches, seizures, deterioration of memory, thinking and other neurological disorders. The consequence of lupus vasculitis of the cerebral vessels can be severe complications in the form.

Systemic lupus erythematosus occurs with periods of exacerbations and remissions (time periods without signs of the disease). Given the lack of treatment methods that can achieve a complete cure, the main goal is to reduce the severity of individual symptoms, slow down the progression of the disease, and achieve stable remission.

Who is at risk?

• Systemic lupus erythematosus is more common in women.
• Persons aged 15-45 years.
• African Americans, Latinos, Asians.
• Persons whose close relatives suffer from systemic lupus erythematosus.

Diagnostics

Diagnosis of systemic lupus erythematosus consists of identifying the characteristic symptoms of the disease, markers of autoimmune reactions specific to it, and conducting a series of studies.

Laboratory research

• Antinuclear antibodies (anti-Sm, RNP, SS-A, SS-B, Scl-70, PM-Scl, PCNA, CENT-B, Jo-1, histones, nucleosomes, Ribo P, AMA-M2), immunoblot. The study allows you to detect specific antibodies to various components of cell nuclei (antigens) of the body. For systemic lupus erythematosus, the presence of antinuclear antibodies anti-Sm, SS-A, PCNA, and antibodies to histones (a type of protein) is specific.
• . This is one of the main methods for detecting antinuclear antibodies - cells of the immune system that aggressively affect the components of the cell nuclei of their own body. Their formation is characteristic of various autoimmune diseases.
• . They are found in autoimmune diseases such as systemic lupus erythematosus, scleroderma, and Sjogren's syndrome. In SLE, their level correlates with the severity of the disease and the likelihood of complications.
• . These antibodies are formed against cell phospholipids (one of the components of cell membranes). Although their presence is more specific for antiphospholipid syndrome, they can be observed in lower concentrations in SLE.
• . Allows you to quantify the main blood parameters. In SLE, the level is reduced.
• . Nonspecific indicator of various pathological processes. In SLE, ESR is elevated due to an autoimmune inflammatory process.
• Microscopy of a blood smear. Examination under a microscope of a preparation made from a drop of blood. In SLE, altered neutrophils (a type of white blood cell) are found in it.
• . The basic physicochemical properties of urine and the presence of physiological and pathological impurities in it are assessed. When the kidneys are damaged, protein and red blood cells are found in the urine due to the development of lupus glomerulonephritis.
• . Sensitive marker of active inflammation and tissue damage. In SLE, its level is elevated.

Damage to various organs in SLE requires a comprehensive laboratory examination to assess various vital signs (for example, determination of parameters of kidney and liver function).

Other studies

• Computed tomography (CT). Allows you to obtain highly accurate layer-by-layer images of internal organs, which has great diagnostic value in identifying the extent of damage to internal organs in SLE (for example, when diagnosing lesions in the brain).
• Radiography. Can be used in SLE to detect pathological changes in the lungs and joints.
• Echocardiography. A method for studying the heart muscle based on the properties of ultrasound. This study allows you to visualize the functioning of the valvular apparatus of the heart, identify signs of myocarditis, pericarditis, which is necessary for diagnosing cardiac complications of SLE.

Treatment

Treatment is aimed at reducing the severity of individual symptoms of the disease and slowing its progression. For this purpose, drugs from several groups are prescribed:

• non-steroidal anti-inflammatory drugs – have analgesic, anti-inflammatory effects;
• glucocorticoids – preparations of hormones of the adrenal cortex; have a pronounced anti-inflammatory effect;
• immunosuppressants – reduce the activity of the immune system, thereby slowing down autoimmune processes and disease progression;
• antimalarial drugs - used for therapy, some of them are effective in the treatment of systemic lupus erythematosus.

Prevention

There are no specific methods for preventing systemic lupus erythematosus.

• Antinuclear antibodies (anti-Sm, RNP, SS-A, SS-B, Scl-70, PM-Scl, PCNA, CENT-B, Jo-1, histones, nucleosomes, Ribo P, AMA-M2), immunoblot

Literature

Dan L. Longo, Dennis L. Kasper,J. Larry Jameson, Anthony S. Fauci, Harrison's principles of internal medicine (18th ed.). New York: McGraw-Hill Medical Publishing Division, 2011. Chapter 319. Systemic Lupus Erythematosus.

Antibodies to nucleoproteins can be determined using immunological reactions.

1. Test to detect LE cells. In 1948, Hargraves et al. In bone marrow and peripheral blood smears of SLE patients, leukocytes with special inclusions, which were called LE cells, were found during incubation at 37°C. Haserick et al. showed that similar cells appear in cases where leukocytes from healthy individuals are incubated with serum or plasma from SLE patients. The LE cell test is positive in 75% of cases. They are especially often identified in the acute period. LE cells are not specific for SLE, but the more often a positive test is reproduced in repeated studies, the higher the likelihood of this diagnosis.

In a small percentage of cases, this phenomenon is also found in other diseases accompanied by the production of ANF. The latter belong to the IgG class antibodies. According to most authors, the responsible antigen is the structure of nucleoproteins; other researchers attach particular importance to antibodies to DNA.

There are two phases in the LE phenomenon:

A) immunological. Cell damage with deformation (swelling) of the nucleus and loss of chromatin, basophilia, which serves as a prerequisite for the manifestation of antibody activity. This is followed by the fixation of antibodies on the nucleus, which is masked due to the negative charge of nucleic acids;

B) nonspecific. The nuclear material in the form of a grayish-smoky mass is phagocytosed by cells that become typical for lupus erythematosus. Complement has a certain significance both during the influence of antibodies and during phagocytosis. The LE phenomenon is a consequence of both the antibody response and phagocytosis of opsonized material from cell nuclei. Phagocytes are primarily polymorphonuclear neutrophils, and less commonly eosinophilic and basophilic granulocytes. The so-called free particles have a variety of shapes. They can be homogeneously or inhomogeneously colored. In some cases, these are altered non-phagocytosed nuclei, and in others, they are nuclear structures that have already been phagocytosed and emerged from destroyed phagocytes. Large, hematoxylin-stained structures result from flocculation. The same happens in tissues.

In vivo, LE cells are present in peripheral blood, non-ricardial and pleural effusions, and in skin lesions.

The LE cell test has the following modifications:

Direct test using blood and bone marrow samples from the patient;

Indirect test using donor leukocytes as a substrate to analyze the patient's serum and assess phagocytosis.

In practice, a direct version of the test is usually used. The Rebuck method is also informative.

2. Rosette reaction. The observed rosettes consist of round or irregularly shaped LE particles surrounded by polymorphonuclear granulocytes. Probably, the central structures represent an intermediate stage between “loose bodies” and LE cells.

3. “B cells” according to Heller and Zimmermann resemble typical LE cells, but the inclusions are less homogeneous, so the differences in color between the inclusions and the nuclei of phagocytic cells are weakly expressed.

4. Nucleophagocytosis, i.e. detection of phagocytosis of nuclei without typical changes in their structures, which has no diagnostic value for SLE.

5. Other methods for detecting antibodies to nucleoproteins: RSC, Friou immunofluorescence, as well as agglutination of carrier particles conjugated with nucleoproteins. In general, there is a clear correlation with the test for LE cells.

The configuration of nucleoproteins acting as antigens is still unknown. Tan et al., using phosphate buffer, extracted the soluble fraction of nucleoprotein from calf thymus cells. This antigen reacted with antibodies to nucleoproteins from SLE patients, as well as some RA patients. After treatment of the drug with trypsin and deoxyribonuclease, antigenicity was lost. The authors suggested that both histones and DNA are involved in the formation of antigenic determinants, but most antibodies to nucleoproteins react with insoluble nucleoproteins and give homogeneous fluorescence. Antibodies to the soluble fraction of nucleoproteins are characterized by predominantly peripheral coloring (binding), which is also characteristic of antibodies to DNA. Anti-DNA sera mostly contain antibodies to nucleoproteins.

Antibodies to DNA. As analysis of experimental data has shown, native DNA is a rather weak antigen. When using denatured DNA and an adjuvant, it is possible to induce the production of antibodies. This explains why anti-DNA antibodies studied in SLE react partly with denatured DNA, partly with native DNA, and sometimes with both. The latter are heterogeneous. Antigen binding sites include a sequence of five bases (among which guanosine plays a special role) and are obviously located in different areas of the macromolecule. Adenosine and thymidine are likely to be of particular importance. Antibodies to denatured DNA often react with denatured RNA.

Antibodies to DNA deserve close attention, as they are highly specific for SLE. To decide whether they are directed against native or denatured DNA, a passive agglutination reaction is used (the antigen is pre-conjugated to a carrier: latex or erythrocytes). This is a fairly sensitive method, giving a positive result in 50-75% of cases. Using direct precipitation in an agar gel, positive results are obtained only in 6-10% of cases, and with immunoelectrophoresis - in 35-80% of cases. Evidence of the production of antibodies to native DNA is of practical importance, since this phenomenon is highly specific for SLE. For this purpose, RIM or immunofluorescence is used. The first test uses labeled DNA. After the addition of Ab-containing serum, separation of free and bound DNA occurs, usually by ammonium sulfate or polyethylene glycol precipitation, filtration through millipore filters (cellulose), or using the double antibody technique. The latter method is more specific, since it eliminates the influence of nonspecific binding of the main protein on DNA. The ability to bind sera of patients with SLE can be 30-50 times higher than that of healthy individuals. Critical factors are the different molecular weight of DNA, as well as the presence of denatured DNA and other proteins. In practice, the “solid phase” technique is often used: DNA is fixed on the surface of plastic or cellulose. At the second stage, incubation with the test serum is carried out. To bind antibodies, labeled anti-Ig is used. The origin of DNA does not play a significant role in these reactions. When antigen-antibody complexes are separated, some denaturation always occurs. Conventional purification methods do not guarantee the complete elimination of this DNA. Bacteriophage DNA is much more stable. The ELISA technique can be used in a similar way.

Thanks to the use of trypanosomes or Crithidia luciliae, it is possible to detect antibodies to DNA by immunofluorescence. In these flagellates, DNA is localized in giant mitochondria. With appropriate processing and the use of indirect immunofluorescence, only DNA antibodies can be detected. The sensitivity of this test is slightly lower than RIM. Using anti-C3 serum labeled with fluorescein isothiocyanate, C-linked antibodies to DNA can be detected, which is obviously valuable for determining the activity of the process.

Antibodies to native DNA have diagnostic value almost only in SLE (in the acute period in 80-98%, in remission - 30-70%); only sometimes they are found in certain forms of uveitis. In other diseases, the question is debated whether we are talking specifically about antibodies to native DNA. A high titer is not always combined with pronounced activity of the process. A simultaneous change in complement concentration suggests kidney damage. IgG antibodies probably play a greater pathogenetic role than IgM. A single positive test for the detection of antibodies to DNA allows one to draw a diagnostic, but not a prognostic conclusion, and only the maintenance of an elevated level of these antibodies over a long period of time can be regarded as a prognostically unfavorable sign. A decrease in level predicts remission or (sometimes) death. Some authors note a more pronounced correlation between the activity of the process and the content of complement-fixing antibodies.

When immunofluorescence, antibodies to DNA are detected mainly along the periphery of the nucleus, but sometimes they are distributed in other areas in the form of a delicate mesh formation. Using fairly sensitive methods, it is possible to detect DNA in serum with a concentration of up to 250 mg/l.

Antibodies to RNA, or antiribosomal antibodies, are found in 40-80% of SLE patients. Their titer does not depend on the level of antibodies to DNA and the degree of activity of the process. Much less frequently, antibodies to RNA are detected in Myasthenia gravis, scleroderma, rheumatoid arthritis, including Sjögren's syndrome, as well as among relatives of the patient and in healthy individuals. They react with both native and synthetic RNA. In other diseases they almost never occur. In Sharp's syndrome, antibodies predominantly to RNP are detected. Antibodies in SLE are relatively heterogeneous and react predominantly with uridine bases, and in scleroderma - with uracil bases of RNA. Antibodies to synthetic polyriboadenylic acid are found in 75% of patients with SLE, 65% of patients with discoid lupus, and 0-7% of patients with other connective tissue diseases. Antibodies are often detected in relatives of patients with SLE (mainly IgM). Ribosomal antibodies react in some cases with free ribosome RNA.

Antibodies to histone. Histones are a mixture of low molecular weight proteins that bind DNA through their base structures. Antihistone Abs are detected in lupus (primarily drug-induced) and RA. They exhibit somewhat different specificities. Thus, in SLE, these antibodies are directed mainly against HI, H2B and H3. They are detected in 30-60%, and in low titers even in 80% of patients. Antibodies to H2B are associated with photosensitivity. In prokainamid-induced lupus, the detected ANFs are directed primarily against histones. In clinical manifestations, these are mainly IgG antibodies to the H2A-H2B complex; in asymptomatic conditions, these are IgM antibodies, in which their specificity to a certain class of histones cannot be recognized. The highest titer of antihistone antibodies has been described in rheumatoid vasculitis (this is only partly due to cross-reacting RF). Highly sensitive methods, such as immunofluorescence, RIM, ELISA, immunoblotting, allow analysis using the most purified histones. Antibodies to histones are not species or tissue specific.

Antibodies to non-histone proteins- to extractable nuclear antigens. The antigen responsible is heterogeneous. Its main fragments are Sm and RNP antigens. There are probably other fractions, as evidenced by immunoelectrophoresis data using rabbit and calf thymus extracts.

Immunofluorescence demonstrates the pattern of the spot. The localization of antibodies is quite difficult to establish. The entire pool of antibodies to non-histone proteins can be determined in the passive agglutination test and RSK. Positive results were obtained for SLE in 40-60%, for rheumatoid arthritis - in 15.5% and for other connective tissue diseases - in 1% of cases. Sharpe's syndrome occupies a special place.

The antigen is extracted from the cell nuclear fraction using phosphate buffer. It is stable to ribo- and deoxyribonucleases, trypsin, ether, and heating to 56 °C. Chemically, it is a glycoprotein. In SLE, antibodies to the Sm antigen are detected in almost 30% of cases through precipitation in the gel and passive agglutination, and vice versa: when these antibodies were detected, 85% of the subjects had systemic lupus erythematosus.

Sm antibodies precipitate five small RNAs (U1, U, U4-U6). RNP antibodies recognize the 5s nucleotide sequence along with a specific polypeptide structure. In fact, splicing can be blocked using antibodies, but there is still no data indicating a pathogenetic role for these mechanisms. According to new research, the binding sites for two types of antibodies are located on the same molecule, with different epitopes. Sm-Ar may also be present in free form. Sm antibodies bind to a nucleotide sequence close to the protein structure.

Antibodies to centromere antigens directed against the kinetostructures of the centromere. The antigen is detected in metaphase. For its detection, rapidly dividing cell lines are most suitable, for example, the HEp-2 line obtained from cultured laryngeal carcinoma cells.

RM-1-complex. Apparently, this is a heterogeneous antigen that is sensitive to heat and trypsin treatment. A high content was noted in the thymus gland of calves, in particular, also in the nucleoli. Antibodies to this antigen are found in the combination of polymyositis and scleroderma in 12% of cases, with polymyositis in 9% and scleroderma in 8% of cases. Sometimes PM-1 antibodies are the only type of autoantibodies detected and thus are of particular diagnostic value. Previously reported high levels of these antibodies were caused by the presence of impurities.

PCNA. Antibodies to this antigen were detected by polymorphic immunofluorescence using a cell line.

Mi-system. As relatively new studies have shown, IgG functions as an antigen, but in a slightly modified form, but an attempt to identify antibodies using rheumatoid factor in reactions was unsuccessful. The question of the diagnostic value of antibodies can be considered unfounded.

Antibodies to nucleoli also detected in SLE (approximately 25% of cases), but much more often (more than 50%) and in high titer in the generalized form of scleroderma, in addition, in almost 8% of patients with rheumatoid arthritis.

To assess the immune system of SLE patients, it is advisable to determine the level of antibodies to DNA and complement activity. An extremely low level of the latter with a fairly high titer of complement-fixing antibodies to DNA indicates an active phase of the disease involving the kidneys. A decrease in complement titer often precedes clinical crisis. The level of IgG antibodies (to DNA and RNA) is especially correlated with the activity of immune reactions in SLE.

Treatment with corticoids and immunosuppressants often results in a rapid decrease in DNA-binding capacity, which may be explained not only by a decrease in antibody production. Anti-DNA antibodies are sometimes detected in dosage forms, particularly in hydralazine treatment.

In RA, SLE-like forms of the disease are often identified, in which LE cells are detected. In accordance with this, immunofluorescence is observed and antibodies to nucleoproteins are determined. In exceptional cases, antibodies to DNA are detected, in which case a combination of two diseases is possible. ANF ​​in rheumatoid arthritis most often belong to class M immunoglobulins.

In scleroderma, ANF is also quite often detected (60-80%), but their titer is usually lower than in RA. The distribution of immunoglobulin classes corresponds to that in SLE. In 2/3 of cases, fluorescence is spotty, in 1/3 - homogeneous. The fluorescence of the nucleoli is quite characteristic. In half of the observations, antibodies bind complement. Noteworthy is a certain discrepancy between the positive results of the general determination of ANF and the absence or production of low titre antibodies to nucleoproteins and DNA. This shows that ANF are mainly directed against substances that do not contain chromatin. There is no relationship between the presence of ANF and the duration or severity of the disease. Most often, correlations are found in those patients whose serum also contains rheumatoid factor.

In addition to rheumatic diseases, ANF is found in chronic active hepatitis (30-50% of cases). Their titer sometimes reaches 1:1000. According to various authors, with discoid lupus erythematosus, ANF is detected in a maximum of 50% of patients.

Immunofluorescence is an almost ideal screening method. When the Ab titer is below 1:50, it is not very informative (especially in elderly people). Titers above 1:1000 are observed only in SLE, lupoid hepatitis and sometimes in scleroderma. Antibodies to nucleoproteins are most often detected (94%). An informative test is the detection of antibodies to DNA.

The abbreviation SLE stands for “systemic lupus erythematosus.” This is a disease that is autoimmune in nature. The mechanism of development of the pathology is the disruption of the functioning of B and T lymphocytes. These are cells of the immune system, the malfunction of which leads to excessive production of antibodies. In other words, the body’s defenses begin to mistakenly attack its own tissues, mistaking them for foreign ones. Immune complexes formed by antibodies and antigens settle in the kidneys, skin and serous membranes. As a result, the development of a number of inflammatory processes starts in the body. SLE, diagnosis and treatment of the disease, as well as possible complications are described below.

Causes

At present, the exact etiology of the pathology has not been established. During the diagnosis of SLE, antibodies to the Epstein-Barr virus were detected in the biomaterial of most patients. Doctors concluded that systemic lupus erythematosus is viral in nature.

In addition, doctors have established some other patterns:

• The most susceptible to the disease are people who, for various reasons, are forced to stay for a long time in regions with unfavorable temperature conditions.
• People whose close relatives suffer from the disease are at risk. Thus, genetic predisposition is also a provoking factor.
• According to the results of numerous studies, SLE is a peculiar reaction of the body to the active vital activity of stimuli. The latter can be any pathogenic microorganisms. However, a malfunction of the immune system does not occur after a single irritation, but against the background of regular negative effects.
• There is a version that the development of systemic lupus erythematosus occurs when the body is intoxicated with certain chemical compounds.

Some doctors believe that SLE is hormonal in nature. However, this theory has not been confirmed by relevant research. However, any hormonal disturbances worsen the course of the disease. Smoking and drinking alcoholic beverages are also risk factors.

Regardless of the causes of SLE (systemic lupus erythematosus), diagnosis and treatment of the disease are carried out according to a standard algorithm.

The pathology is characterized by a wide range of symptoms. SLE is chronic in nature, that is, episodes of exacerbation are regularly followed by periods of remission. The disease affects most organs and systems, causing characteristic clinical manifestations.

Main symptoms of the disease:

• Constant feeling of fatigue.
• Reducing body weight.
• Rapid onset of fatigue.
• Increased body temperature.
• Decreased performance.
• Arthritis. The knees, wrists and knuckles are most often affected.
• Osteoporosis.
• Pain and weakness in muscle tissue.
• Erythema on exposed skin. Typically the face, shoulders and neck are affected.
• Alopecia in a limited area (in most cases, hair loss occurs in the temporal areas).
• Photosensitivity.
• Damage to mucous membranes.
• Pleurisy.
• Lupus pneumonitis, which is characterized by shortness of breath and cough, accompanied by the discharge of sputum mixed with blood.
• Pulmonary hypertension.
• Pericarditis.
• Pulmonary embolism.
• Myocarditis.
• Kidney damage.
• Headache.
• Hallucinations.
• Psycho-emotional instability.
• Neuropathy.
• Painful sensations in the epigastric zone.
• Nausea.
• Anemia.

This is not the entire list of clinical manifestations. The disease can affect any internal organs, causing symptoms characteristic of their damage. Since the disease does not have specific symptoms, differential diagnosis of SLE is mandatory. Only based on the results of a comprehensive examination can a doctor confirm the development of the disease and draw up a treatment plan.

Diagnostic criteria

Doctors developed a list of the main clinically significant manifestations of the pathology. The disease is confirmed if the patient has at least 4 out of 11 conditions.

Diagnosis criteria for SLE:

1. Arthritis. It is peripheral in nature without the formation of erosions. It manifests itself as painful sensations and swelling. A small amount of fluid is visualized in the joint area.
2. Discoid rash. It has an oval or ring shape. The color of the rash is red. The contours of the plaques are uneven. On the surface of the spots you can find scales that are difficult to separate.
3. Damage to mucous membranes. Manifests itself in the form of painless lesions in the oral cavity or nasopharynx.
4. High sensitivity to ultraviolet light.
5. The presence of a specific rash on the cheeks and wings of the nose. Outwardly, it resembles the outline of a butterfly.
6. Kidney damage. It is characterized by the excretion of protein from the body along with urine.
7. Damage to the serous membranes. It manifests itself as pain in the chest area, the intensity of the discomfort intensifies as you inhale.
8. A central nervous system disorder characterized by muscle cramps and psychosis.
9. Changes in the blood. Identified during the diagnosis of SLE by analysis.
10. Changes in the functioning of the immune system.
11. Increase in the rate of specific antibodies in biological material.

Determination of disease activity index

The SLEDAI system is used in the diagnosis of SLE. It involves assessing the course of pathology using 24 parameters. Each of them is expressed in points (points).

Evaluation criteria according to the SLEDAI system:

1. Presence of convulsive seizures not accompanied by disturbances of consciousness - 8 points.
2. Psychosis - 8.
3. Changes in the brain of an organic nature (impaired orientation in space, memory impairment, insomnia, incoherent speech) - 8.
4. Inflammation of the optic nerve - 8.
5. Primary damage to cranial nerve cells - 8.
6. Headache that does not subside even after taking narcotic analgesics - 8.
7. Impaired blood circulation in the brain - 8.
8. Vasculitis - 8.
9. Arthritis - 4.
10. Myositis - 4.
11. Cylinders in urine - 4.
12. More than 5 red blood cells in the urine - 4.
13. Protein in urine - 4.
14. More than 5 leukocytes in urine - 4.
15. Inflammation of the skin - 2.
16. Alopecia - 2.
17. Ulcerative lesions of the mucous membranes - 2.
18. Pleurisy - 2.
19. Pericarditis - 2.
20. Decrease in compliment C3 or C4 - 2.
21. Positive antiDNA - 2.
22. Increased body temperature - 1.
23. Decrease in the level of platelets in the blood - 1.
24. Decrease in leukocytes - 1.

The maximum result is 105 points. It indicates an extremely high degree of disease activity, when all major systems are affected. Doctors make the same conclusion when the result is 20 or more points. A score of less than 20 points is considered to indicate a mild or moderate degree of activity.

Laboratory diagnosis of SLE

To confirm or exclude the development of the disease, doctors prescribe many tests. Diagnosis of SLE using blood tests is possible, but in any case it is necessary to carry out a number of instrumental studies.

Laboratory methods:

• ANA test. Involves detection If its titer exceeds 1:160, it is customary to talk about the development of an autoimmune pathology in the body.
• AntiDNA. Antibodies are detected in half of patients.
• Anti-Sm. A test that detects antibodies to a special Smith antigen.
• Anti-SSA (SSB). These are antibodies to proteins. They are not specific for SLE and can also be detected in other systemic pathologies.
• Analysis for anticardiolipin.
• Blood test for antihistones.
• The presence of markers of the inflammatory process (increased ESR and C-reactive protein).
• Reducing the level of compliment. This is a group of proteins that are directly involved in the formation of the immune response.
• A complete blood count is not significant in the laboratory diagnosis of SLE. The level of lymphocytes, red blood cells, platelets and white blood cells may decrease slightly.
• Urine examination. In SLE, the following are observed: proteinuria, pyuria, cylindruria and hematuria.
• Blood chemistry. Alarming results are: increased creatinine, AST, ALAT and creatine kinase.

Even if the tests for diagnosing SLE are disappointing, instrumental methods are prescribed in any case. Based on the results of a comprehensive examination, the disease is confirmed or excluded.

Instrumental methods

To diagnose SLE, the doctor prescribes:

• X-ray of the joints. Allows you to detect minor changes in bone structures.
• X-ray and CT scan of the chest.
• Angiography and nuclear magnetic resonance. The study allows you to identify damage to the nervous system.
• Echocardiography. It is carried out to assess the functioning of the heart muscle.

If necessary, specific studies may be prescribed. When diagnosing SLE, doctors often resort to spinal taps and skin and kidney biopsies.

Differential diagnosis

Based on a detailed examination and careful history taking. Also important in diff. Diagnosis of SLE involves establishing the pathogenesis of the patient’s clinical manifestations. This is due to the fact that in many cases the symptoms are associated with the course of another disease, which significantly influences the choice of treatment regimen.

Systemic lupus erythematosus must be differentiated from:

• Anemia.
• Hypothyroidism.
• Viral infections.
• Intoxication of the body due to taking medications.
• Rosacea.
• Dermatitis.
• Photosensitive eczema.
• Persistent monoarthritis.
• Aseptic necrosis.
• Heart failure.
• Diabetes mellitus.
• Arterial hypertension.
• Infectious diseases of the genitourinary system.
• Thrombosis of renal vessels.
• Brain tumors.
• Infectious pathologies of the central nervous system.
• Meningitis.
• Multiple sclerosis.
• Miliary tuberculosis.

Thus, to make an accurate diagnosis, the most correct assessment of symptoms that reflect the degree of activity of the underlying disease is necessary.

Treatment

Despite significant progress in finding an effective method of therapy, it is impossible to get rid of the disease. The goal of all measures is to relieve the acute stage, get rid of unpleasant symptoms and prevent the development of complications.

A rheumatologist diagnoses and treats SLE. If necessary, he arranges a referral for consultation with other specialists of a narrow profile.

The standard treatment regimen for systemic lupus erythematosus includes the following:

• Reception and intravenous administration of glucocorticosteroids (for example, Prednisolone).
• Combined pulse therapy. Involves the simultaneous use of a cytostatic drug and a glucocorticosteroid. The first include the following drugs: Methotrexate, Cyclophosphamide.
• Taking anti-inflammatory drugs (Aertal, Nimesil).
• Administration of drugs belonging to the aminoquinoline series (Plaquenil).
• Taking biological agents that affect the mechanisms of development of autoimmune pathologies. These drugs are effective, but very expensive. Examples of drugs: Gumira, Rituximab, Embrel.
• Taking anticoagulants, diuretics, antiplatelet agents, potassium and calcium supplements.

In severe cases of SLE, the doctor makes a decision regarding the advisability of extracorporeal treatment methods (plasmapheresis and hemosorption).

All patients, without exception, must avoid getting into stressful situations and stay in direct sunlight for a long time.

Forecast

It directly depends on the timeliness of visiting a doctor and the severity of the disease. Systemic lupus erythematosus in its acute form develops at lightning speed, most internal organs are affected almost instantly. Fortunately, this situation is extremely rare; it always leads to complications and often causes death.

The chronic option is considered the most favorable. This is due to the fact that the disease progresses slowly, and internal organs are gradually affected. However, SLE even in chronic form can lead to irreversible consequences. In most cases, this is due to ignoring the problem and non-compliance with the recommendations of the attending physician.

Life-threatening complications include: renal failure, myocardial infarction, cardiosclerosis, pericarditis, cardiac and respiratory failure, thromboembolism and pulmonary edema, intestinal gangrene, stroke, internal bleeding.

Finally

This is an autoimmune disease. The pathogenesis of the disease has not yet been established, but it is known that the mechanism of development of the pathology is an erroneous attack of the body’s defense system of its own cells.

SLE has no specific symptoms; there are so many clinical manifestations of the disease that a thorough comprehensive examination is necessary. Diagnosis of pathology involves the implementation of laboratory and instrumental techniques, as well as differentiating the disease from other possible pathologies.

Lupus is a fairly common autoimmune disease: for example, it affects approximately one and a half million people in the United States. This disease affects various organs such as the brain, skin, kidneys and joints. Symptoms of lupus can be easily confused with those of other diseases, making it difficult to diagnose. It's helpful to know the symptoms and diagnosis of lupus so it doesn't catch you by surprise. You should also be aware of the causes of lupus to avoid potential risk factors.

Attention: The information in this article is for informational purposes only. If you experience any of the following symptoms, consult your doctor.

Steps

Lupus symptoms

Check to see if you have a butterfly wing rash on your face. On average, 30 percent of people with lupus develop a characteristic rash on their face, which is often described as being shaped like a butterfly or a wolf bite. The rash covers the cheeks and nose and sometimes extends all the way to the eyes.

• Also check for disc-shaped rashes on your face, scalp and neck. This rash appears as red, raised spots and can be so severe that it leaves scars.
• Pay special attention to rashes that appear or worsen when exposed to sunlight. Sensitivity to natural or artificial ultraviolet radiation can cause a rash on sunlit areas of the body and worsen the butterfly rash on the face. This rash is more abundant and appears faster than with a regular sunburn.

1. Check for ulcers in the mouth and nasal cavity. If you often have ulcers on the roof of your mouth, the corners of your mouth, your gums, or your nose, this is another warning sign. Pay special attention to painless sores. Typically, with lupus, sores in the mouth and nose do not hurt.

   • Photosensitivity of ulcers, that is, their aggravation by exposure to sunlight, is another sign of lupus.

2. Look for signs of inflammation. People with lupus often experience inflammation of the joints, lungs, and tissues around the heart (the pericardial sac). Usually the corresponding blood vessels become inflamed. Inflammation can be identified by swelling of the feet, legs, palms and eyes.

   Pay attention to your kidney function. Although it is difficult to assess the condition of the kidneys at home, it can still be done based on some signs. If lupus causes your kidneys to be unable to filter urine, your feet may become swollen. Moreover, the development of renal failure may be accompanied by nausea and weakness.

   Take a closer look at possible problems with the brain and nervous system. Lupus can affect the nervous system. Some symptoms, such as anxiety, headaches and vision problems, are also observed in many other diseases. However, lupus can also cause very serious symptoms such as seizures and personality changes.

   • Although lupus is often accompanied by headaches, this pain is very difficult to identify the disease. Headache is a common symptom and can be caused by a variety of reasons.

3. See if you feel tired more often than usual. Extreme fatigue is another sign of lupus. Although feeling tired can have a variety of causes, often those causes are related to lupus. If fatigue is accompanied by a fever, this is another sign of lupus.

   Look for other unusual signs. When exposed to cold, fingers and toes may change color (turn white or blue). This phenomenon is called Raynaud's disease, and it often accompanies lupus. Dry eyes and difficulty breathing may also occur. If all of these symptoms occur at the same time, you may have lupus.

   Learn about tests that use imaging techniques. If your doctor suspects that lupus may be affecting your lungs or heart, he or she may order a test to see your internal organs. To find out the health of your lungs, you may be referred for a standard chest x-ray, while an echocardiogram will provide insight into the health of your heart.

   • A chest x-ray sometimes shows shadowed areas in the lungs, which may indicate fluid accumulation or inflammation.
   • Echocardiography uses sound waves to measure the heartbeat and identify possible heart problems.

4. Find out about biopsy. If your doctor suspects that lupus has caused kidney damage, he or she may order a kidney biopsy. A sample of your kidney tissue will be taken for analysis. This will allow you to assess the condition of the kidneys, the degree and type of damage. A biopsy will help your doctor determine the best treatment options for lupus.