(Study type: Blood collected in a red-top tube; related body system: Immune and musculoskeletal systems.)

Antinuclear antibodies are autoantibodies mainly located in the nucleus of affected cells. The presence of ANA is a sensitive indicator of SLE, related collagen vascular diseases, or immune complex diseases. Women are much more likely than men to be diagnosed with SLE.

Positive findings for ANA alone lack specificity. Generally a positive ELISA for ANA IgG or IFA ANA titer greater than 1:80 is followed up with tests for other related autoantibodies. The IFA method also provides the ability to identify ANA patterns associated with the qualitative presence of related autoantibodies. Antibodies against cellular DNA are strongly associated with SLE. Anticentromere antibodies are a subset of ANA. Their presence is strongly associated with CREST syndrome (c-alcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia). Jo-1 is an autoantibody found in the sera of some ANA-positive patients. Compared to the presence of other autoantibodies, the presence of Jo-1 suggests a more aggressive course and a higher risk of mortality. The clinical effects of this autoantibody include acute-onset fever, dry and crackled skin on the hands, Raynaud phenomenon, and arthritis. The extractable nuclear antigens (ENAs) include ribonucleoprotein (RNP), Smith (Sm), SS-A/Ro, and SS-B/La antigens. ENAs and antibodies to them are found in various combinations in individuals with combinations of overlapping rheumatological symptoms.

The American College of Rheumatology’s (ACR) current classification (10 elements) begins with a positive ANA study and includes additive weighted scores from a list of seven clinical and three immunological groups of criteria associated with a diagnosis of SLE. The patient should have a score of 10 or more to establish suspicion of lupus. The signs and symptoms do not have to manifest at the same time; they can present serially or simultaneously during any time frame in which they are being evaluated. The sign or symptom is included if other diseases or conditions having the same sign or symptom have been ruled out (e.g., electrolyte imbalance, ketoacidosis, urinary tract infection) or occur in the absence of drugs or substances known to cause it (e.g., drug-induced thrombocytopenia, food- or drug-induced hemolytic anemia).

ACR Classification Criteria

• The classification process begins with a positive ANA, in the absence of a drug known to induce lupus, with a titer at least 1:80 on human epithelial-2–cell media or obtained from an equivalent positive study.
• Clinical areas evaluated:
  1. Constitutional: Fever
  2. Hematological: Autoimmune hemolytic anemia, leukopenia with WBC count less than 4 × 10³/microL, lymphopenia with a lymphocyte count less than 1.5 × 10³/microL, or thrombocytopenia with platelet count less than 100 × 10³/microL
  3. Mucocutaneous: Acute cutaneous lupus, alopecia (nonscarring), oral ulcers, or subacute cutaneous lupus or discoid lupus
  4. Musculoskeletal: Affecting joints (pain, inflammation)
  5. Neuropsychiatric: Delirium, psychosis, or seizures
  6. Renal: Proteinuria (evidenced by urine findings: protein greater than either 3+ or 0.5 g/day), biopsy scored class II or V lupus nephritis, or biopsy scored class III or IV lupus nephritis
  7. Serosal: Pleural or pericardial effusion or pericarditis (acute)
• Immunological groups:
  1. Antiphospholipids: Positive anticardiolipin (IgG) antibodies or positive anti–beta-₂ glycoprotein 1 (IgG) or positive for lupus anticoagulant
  2. Complement proteins: Either C3 or C4 level is below normal limits or C3 and C4 are below normal limits
  3. Antibodies highly specific for SLE: Anti-dsDNA antibody titer greater than 1:10 (using Crithidia luciliae) or positive anti-dsDNA (ELISA) confirmed using Crithidia luciliaeor positive anti-Smith antibody

The ACR favors the consideration of classification criteria rather than endorsement of diagnostic criteria for SLE because of the difficulty in establishing a consistent set of criteria. SLE is a disease whose cause is complex, is influenced by numerous factors, and may only intermittently display previously documented signs and symptoms. The diagnosis of SLE is made for patients on an individual basis by considering the ACR’s classification criteria in the presence of additional information unique to the patient and to the patient’s lifestyle and environment.