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Anti-Neutrophil Cytoplasmic Antibodies (ANCA)

Anti-Neutrophil Cytoplasmic Antibodies (ANCA). Ted Brown CP Case Conference February 24, 2012. ANCA. Antibodies against neutrophil cytoplasmic antigens Most common targeted antigens are myeloperoxidase (MPO) and proteinase 3 (PR3) Prevalent among adults in 50s and 60s, M=F.

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Anti-Neutrophil Cytoplasmic Antibodies (ANCA)

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  1. Anti-Neutrophil Cytoplasmic Antibodies(ANCA) Ted Brown CP Case Conference February 24, 2012

  2. ANCA Antibodies against neutrophil cytoplasmic antigens Most common targeted antigens are myeloperoxidase (MPO) and proteinase 3 (PR3) Prevalent among adults in 50s and 60s, M=F We perform 2 assays: • Indirect immunofluorescence assay: normal human neutrophils (sensitive) • Enzyme-linked immunosorbent assay: specific antigen (specific)

  3. When is ANCA testing ordered? Clinical suspicion of systemic autoimmune vasculitis Symptoms nonspecific in early disease (fever, fatigue, aches) to more diffuse in later disease (proteinuria, cough, rash/granuloma, runny nose, peripheral neuropathy, pulmonary hemorrhage and hemoptysis) Integrate clinical and laboratory info ANCA, ANA, complement, cryoglobulins, hepatitis B and C, rheumatoid factor, azotemia, hematuria, proteinuria, recent drug history

  4. Indirect Immunofluorescence Patient sera on ethanol fixed PMNs

  5. Indirect Immunofluorescence Patient sera on ethanol fixed PMNs

  6. Indirect Immunofluorescence Patient sera on formalin fixed PMNs

  7. ELISA If indirect immunofluorescence microscopy positive, perform ELISA Determine amount of antibody present: Titer determined by serial dilutions PR3 and MPO antibodies

  8. Diseases with ANCA C-ANCA and PR3: Wegener’s (90% in active, generalized granulomatous and polyangiitis disease; 60-70% in no active disease) P-ANCA and MPO: Microscopic polyangitis (70%), Churg –Strauss (50%), drugs ANCA-positivity also seen in other diseases, including gastrointestinal disorders • 60-80% with ulcerative colitis and related disorder primary sclerosing cholangitis • <30% in Chron’s disease

  9. Patient Case 48 year old female with known leukocytoclastic vasculitis and ulcerative colitis Recent use of cocaine Increased arthralgias No history of ANCA testing

  10. Cocaine and ANCA vasculitis ~70% of cocaine bought illicitly in US contaminated with levamisole Levamisole-contaiminated cocaine associated with ANCA vasculitis Clinical symptoms: arthralgias, skin lesions, fever.

  11. Clinical Applications of ANCA testing Positive test really a true positive? + Immunofluorescence and ELISA= PPV increased to 88% Negative test a true negative? Clinical presentation key Need for a tissue biopsy? Controversial: reasonable attempts should be made to obtain histologic proof due to long-term treatment commitment with toxic medications. Use of titers? Do not use as sole parameter to guide therapy.

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