The diagnosis of SLE relies on clinical manifestations, laboratory tests, histopathology and imaging. In the classification criteria for SLE revised by the American College of Rheumatology (ACR) in 1997, laboratory tests such as hematologic abnormalities, immunologic abnormalities and positive autoantibodies were clearly included in the diagnostic criteria. Laboratory tests for SLE are important for its diagnosis, differential diagnosis and determination of activity and relapse. (1) Routine examination: Since SLE patients can often have involvement, such as hematological system abnormalities and kidney damage, routine blood examination may show anemia, leukopenia and reduced platelets; when the kidneys are involved, urinalysis may show proteinuria, hematuria, cells and granular tubularity; erythrocyte sedimentation rate (hematocrit) increases during the active phase of SLE, while it mostly decreases to normal during the remission phase. (2) Immunological examination: 50% of SLE patients have hypoalbuminemia, 30% of patients have hyperglobulinemia, especially elevated gamma globulin, and serum IgG levels during active disease. When the disease is active, complement levels are reduced due to the depletion of complement by immune complex formation and the decreased ability of the liver to synthesize complement. Individual complement components C3, C4 and total complement hemolytic activity (CH50) can be reduced during the active phase of the disease. (3) Biochemical tests: liver function tests in SLE patients are mostly mild to moderate abnormalities, more often seen during active disease, accompanied by elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Abnormalities in serum albumin tend to indicate renal failure. Quantification of urine microalbumin in renal function tests can help determine and monitor the degree of kidney damage and prognosis. When lupus nephritis occurs, serum urea nitrogen (BUN) and serum creatinine (Cr) can help determine the clinical stage and observe the treatment effect. Some patients with SLE have severe dyslipidemia and elevated inflammatory markers, along with hyperhomocysteinemia (Hcy). Serum lipid levels, hypersensitive C-reactive protein (hs-CRP) and homocysteinemia are considered to be effective predictors of CTD, and regular testing can identify patients at high risk of cardiovascular events early. (4) Autoantibody testing: At present, the routine tests for SLE-related autoantibodies are mainly anti-nuclear antibodies (ANA), anti-dsDNA antibodies, anti-ENA antibodies (including anti-sm, anti-U1RNP, anti-SSA/Ro, anti-SSB/La, anti-rRNP, anti-Scl-70 and anti-Jo-1, etc.), anti-nucleosome antibodies and antiphospholipid antibodies. Autoantibody testing should be performed in patients with a clinical suspicion of SLE. In the revised classification criteria for SLE by the American College of Rheumatology, immunological abnormalities and autoantibody positivity include anti-Sm antibody, anti-dsDNA antibody, antiphospholipid antibody and ANA positivity. (5) Histopathological examination: skin biopsy and renal biopsy are also very helpful for the diagnosis of SLE, and the positive skin lupus band test and the glomerular manifestation of “fullness” have high specificity. 2.What are the laboratory indicators to determine the activity and relapse of SLE? There are various clinical manifestations when SLE is active or relapsing, but the changes in laboratory tests and clinical symptoms are synchronized in most patients, therefore, the combination of laboratory tests can more clearly determine the disease activity and decide the treatment plan. At present, there are various systems for determining the activity of SLE disease. The laboratory tests include routine blood, urine, immunological routine (complement and C-reactive protein), autoantibodies (anti-ds-DNA), and biochemical routine (liver and kidney function), etc. 3.What is autoantibody? Autoimmune disease (AID) refers to a disease in which the body’s immune effector cells or immune effector molecules produce a pathological immune response against its own tissues or cells, and the autoimmune response is involved in the pathogenesis, leading to tissue damage or dysfunction. Autoantibody testing is essential for the diagnosis and differential diagnosis of AID, and autoantibodies have become the most important feature of autoimmune diseases. The existence of autoantibodies has been recognized since the phenomenon of lupus cells (LE cells) was first described by Hargraves in 1948. Autoantibodies are immunoglobulins against intracellular, cell surface and extracellular antigenic components of self. Autoantibodies are one of the important features of autoimmune response and autoimmune diseases, and most autoimmune diseases are accompanied by characteristic autoantibodies (spectrum) Autoantibody testing has become an important means of diagnosing autoimmune diseases. 4.What is the clinical classification of autoantibodies? Autoantibodies can be clinically classified into: ① Disease marker (Chi) autoantibodies, which are only found in certain autoimmune diseases and rarely in other diseases, and are of great diagnostic value for autoimmune diseases, but are less diverse and less sensitive, such as anti-Sm antibodies (sensitivity 20%-30%), anti-ribosomal P protein (Rrnp) antibodies (sensitivity 20%-30%), and anti-Sm antibodies (sensitivity 20%-30%) in systemic lupus erythematosus (SLE). (sensitivity 20%-30%), anti-proliferative cell nuclear antigen (PCNA) antibodies (sensitivity only 2%-7%). ②Disease-specific autoantibodies, which are highly sensitive in certain autoimmune diseases, can also be found in other diseases but with low sensitivity, such as anti-double-stranded DNA (ds-DNA) antibodies in systemic lupus erythematosus (sensitivity 70%-80% and specificity 90%-95% in active phase), and also in diseases such as type 1 autoimmune hepatitis and mixed connective tissue diseases (sensitivity (sensitivity less than 10%). ③Disease-related autoantibodies, such autoantibodies are closely related to certain autoimmune diseases, but they can also appear in other diseases, and their sensitivity is not low, such as anti-SSA antibodies in primary dry syndrome (pSS), with positive rates of 70% and 40% respectively, which are of great significance for the diagnosis of primary dry syndrome, but they are also often found in systemic lupus erythematosus, with positive rates of 50% and 30% respectively. ④Disease nonspecific autoantibodies, such autoantibodies can be found in a variety of autoimmune diseases and are not specific for disease diagnosis, such as antinuclear antibodies (ANA), which can be found in a variety of connective tissue diseases and are used as screening tests for connective tissue diseases. ⑤ Physiological autoantibodies, autoantibodies against self-antigens are often present in normal people. These autoantibodies are of low potency and are not sufficient to cause damage to their own tissues, but they can assist in the removal of aging and metamorphosis of their own components and play an immune self-stabilizing effect. 5.What is the clinical significance of autoantibody testing? Autoantibody testing has the following clinical significance: ①Diagnosis and differential diagnosis of autoimmune diseases. Different autoimmune diseases have characteristic autoantibody profiles, and disease-marking antibodies, specific antibodies or disease-related autoantibodies are of great significance for the diagnosis and differential diagnosis of autoimmune diseases, and are essential for early disease and timely treatment of autoimmune diseases. For example, anti-dsDNA antibodies, anti-Sm antibodies, anti-ribosomal P protein (rRNP) antibodies and anti-nucleosome antibodies in systemic lupus erythematosus. Certain autoantibodies are closely related to disease activity, and the waxing and waning of autoantibody potency and titer can be used to determine disease activity, observe treatment response, and guide clinical treatment. The autoantibodies commonly associated with disease activity, such as anti-ds-DNA antibodies in systemic lupus erythematosus, should be tested in the laboratory with emphasis on quantitative and regular testing. ③ Autoimmune disease course and prognosis determination, certain autoantibodies are associated with disease progression and regression. ④Research on the pathogenesis of autoimmune diseases, through the practice of clinical application of autoantibodies, the pathogenesis of autoimmune diseases can be further studied and elucidated. 6.What are the autoantibodies related to SLE? What is the value of clinical testing? In 1956, Roitt was the first to discover thyroid antibodies in the first organ-specific autoimmune disease, Hashimoto’s thyroiditis. In 1957, Holborow et al. applied an induction immunofluorescence method to detect antinuclear antibodies, and from then on, a half century of large-scale autoantibody research was launched and the process of clinical application was promoted. So far, more than 2000 autoantibodies have been reported, and the autoantibodies present in SLE alone can reach more than 100. About 100 types of SLE-related autoantibodies have been reported, acting on the nucleus, cytoplasm, cell surface antigens, and components such as complement components and coagulation factors, respectively. Autoantibody testing is important for the diagnosis, differential diagnosis, and activity determination of SLE. Autoantibodies routinely detected in SLE should include: anti-nuclear antibodies (ANA), anti-ds-DNA antibodies, anti-ENA antibodies (including anti-Sm, anti-UIRNP, anti-SSA/Ro, anti-SSB/La, anti-rRNP, anti-Scl-70 and anti-Jo-1, etc.), anti-nucleosome antibodies, anti-synuclein antibodies and antiphospholipid antibodies (including lupus anticoagulant, anti-cardiac antiphospholipid antibodies (including lupus anticoagulant, anti-cardiolipin antibody, anti-β2GPI antibody), etc. For clinical differential diagnosis with other autoimmune diseases, anti-neutrophil cytoplasmic antibody profile (anti-PR3 antibody, anti-MPO antibody), rheumatoid factor (RF), autoantibody profile for early diagnosis of rheumatoid arthritis (anti-CCP antibody), autoantibody profile for autoimmune liver disease (anti-smooth muscle antibody, anti-mitochondrial antibody, etc.) should also be tested. Differentiate from systemic vasculitis, rheumatoid arthritis and autoimmune liver disease, respectively. 7. Is there antinuclear antibody-negative SLE? Anti-nuclear antibody (ANA) is the most common autoantibody in SLE, with a positive rate of up to 95-100%, but the specificity is not high and can be used as a screening autoantibody for SLE. A small percentage of patients meet the diagnostic criteria for SLE and are consistently negative for antinuclear antibodies (ANA); this group accounts for about 2% of all SLE patients and is known as a subtype of SLE. This may be due to the absence of ANA production, the binding of autoantibodies to affected tissues (e.g., skin or kidney tissue), or because they are hidden in circulating immune complexes, or due to remission after the application of adrenocorticotropic hormones and immunosuppressive drugs, or because the patient is hypoproteinemic due to increased depletion of the renal basement membrane as the disease enters the end stage of nephropathy with massive protein excretion from the urine. It was found that non-specific damages such as fever, weight loss, arthralgia, myalgia, Raynaud’s phenomenon, oral ulcers, hair loss and other systemic damages were not significantly different in ANA-negative SLE patients compared with ANA-positive SLE patients; the incidence of pteroidal erythema and photosensitivity was slightly higher but not significantly different; the incidence of hand and foot erythema was significantly higher than that of ANA-positive SLE patients The incidence of anti-SSA/Ro antibodies in the sera of ANA-negative SLE patients was higher, and many studies showed that anti-SSA/Ro antibodies were closely related to photosensitivity, suggesting that anti-SSA antibodies and anti-SSB antibodies are important for SLE and subacute cutaneous lupus erythematosus when ANA-negative is detected by indirect immunofluorescence. The lower rate of positive anti-ds-DNA and anti-Sm antibodies in the serum of patients may be related to the lower odds of renal damage and hematologic damage in ANA-negative SLE patients and the fact that they are mostly quiescent. Overall ANA-negative SLE has less systemic damage and a better prognosis. In clinically suspected SLE patients with negative ANA test, attention should be paid to the detection of other target antigen-specific autoantibodies in the ANA spectrum, such as anti-SSA/Ro antibody, anti-SSB/La antibody, anti-ribosomal P protein (rRNP) antibody, anti-nucleosome antibody, anti-ds-DNA antibody, etc. Attention should also be paid to the detection of other SLE-related autoantibodies, such as lupus anticoagulant, Anti-cardiolipin antibody, anti-β2GPI antibody, anti-C1q antibody, etc. 8.Will SLE antinuclear antibodies turn negative when the disease improves with treatment? In general, ANA is not related to the activity of SLE disease, and its antibody potency does not change with the improvement of treatment, and the ANA titer decreases or turns negative. However, in rare cases, if the SLE patient has only or mainly autoantibodies related to SLE activity (anti-ds-DNA antibodies), the ANA titer will change as the treatment improves, and the ANA titer will decrease or even turn negative.