Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ ANA-ASSOCIATED CONNECTIVE TISSUE DISORDERS ++ Rheumatologic conditions associated with a +ANA: Systemic lupus erythematosus (SLE) Systemic sclerosis (SSc) Myositis (often ANA-negative; ~50% of dermatomyositis/polymyositis cases are ANA-positive) Mixed connective tissue disease (MCTD) Primary Sjögren’s ANA Testing Pearls: - Antinuclear antibodies (ANA) are autoantibodies that bind to the contents of the cell nucleus. The ANA test detects the ANA autoantibodies that are present in the patient’s serum. - ANA can be elevated in many disorders including autoimmune conditions, infection, and malignancy. 20% of healthy women have a positive ANA. Therefore, it is non-specific and should only be sent if clinical suspicion is high for one of the disorders above. - The level of autoantibody is reported as a titer, which is the highest dilution of the serum at which the autoantibodies are still detectable (e.g., 1:640 is more dilute than 1:80, suggesting more autoantibodies are present in the 1:640 sample). The probability of autoimmunity increases with higher ANA titers: ANA ≥1:80 required by EULAR/ACR SLE classification criteria ANA ≥1:640 → 95.8% specific for SLE - If an ELISA-based ANA test is negative but clinical suspicion for CTD high, ask the lab to carry out an immunofluorescence (IF)-microscopy-based ANA test, which is more specific. ++Table Graphic Jump LocationTABLE 9.3Test Characteristics & Clinical Associations for ANA & Sub-SerologiesView Table||Download (.pdf) TABLE 9.3 Test Characteristics & Clinical Associations for ANA & Sub-Serologies Antibody (anti-X) Target Antigen Prevalence Clinical Associations ANA Various (see below) 95% in SLE95% in SSc>80% Sjögren’s>50% PM/DM Non-specific, best screening test for SLE dsDNA dsDNA 70% in SLE 95% specific for SLE. Titer tracks with disease activity in most patients. Associated with nephritis risk. Sm Various proteins that bind to small non-coding RNAs 25% in SLE 99% specific for SLE U1RNP 40% in SLE MCTD (see below) Ro (SS-A) 30% in SLE30–70% Sjögren’s Annular subacute cutaneous lupus rash; congenital heart block. Seen in primary Sjögren’s > RA-associated seconodary Sjögren’s. La (SS-B) 10% in SLE25–40% Sjögren’s Rarely seen in the absence of Anti-Ro. Lower risk of nephritis. Histone Chromatin-associated histones 95% in drug-induced lupus 50–70% in SLE Drug-induced lupus associated with procainamide, hydralazine, isoniazid Centromere Chromosomal kinetochore proteins 15% in SSc60% in CREST Limited cutaneous SSc Scl70 Topoisomerase-I 40% in SSc Diffuse cutaneous SSc + ILD RNA-Pol-III RNA-Pol-III 4–20% in SSc Paraneoplastic SSc (+ test should trigger malignancy work-up), positive in 60% of patients with scleroderma renal crisis Mi-2 Helicase 15–20% in DM DM with fulminant skin > muscle involvement, excellent treatment response, ↓risk of associated malignancy PM-Scl Nucleolar exosome complex 4–12% of SSc PM-SSc overlap syndrome with ILD, nonerosive arthritis, Raynaud’s, mechanic’s hands +++ Systemic lupus erythematosus (SLE) ++ Pathogenesis: - Decreased clearance and increased responsiveness to self-nucleic acids → excessive IFNα production by innate immune cells (especially plasmacytoid dendritic cells) → inappropriate activation of autoreactive B cells → autoantibody production, immune complex deposition in skin, ... Your Access profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth