ANCA Anti-neutrophil cytoplasmic antibodies (ANCAs)


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ANCA Anti-neutrophil cytoplasmic antibodies (ANCAs)

  1. 1. Prepared by Dr. Anees Al-Saadi April 2008Clinical immunology principles and practice RICH, 2nd editionMethodological update ›,
  2. 2.  ANCA auto antibodies related to inflammatory disorders. van der Woude et al. in 1985 showed ANCA related to Wegeners granulomatosis. Methodological update ANCA.mht
  3. 3.  Enzymes used in the defense against bacteria found in WBCs granules. Most reactivities were found molecular weights ≈29kD & l4OkD. Methodological update ANCA.mht
  4. 4.  Two main enzymes in ANCA take part in the killing of bacteria by:  Proteinase 3 (PR3) showing cANCA pattern.  Myeloperoxidase (MPO) showing pANCA pattern. Methodological update ANCA.mht
  5. 5.  Molecular weight of 29kD antigen:  Which is proteinase .  PR3 is a single protein chain that is glycosylated.  Is very similar to other serine proteases like elastase and cathepsin G. Methodological update ANCA.mht
  6. 6.  Myeloperoxidase (MPO)  MPO is a dimer molecular weight of l4OkD consisting of one heavy & light chain .  It is glycosylated with mannose oligosaccharide chains.  Is cleaved by heating and has a green color . Methodological update ANCA.mht
  7. 7.  Many other antigens have been described to be associated with ANCA,  i.e. elastase,  lactoferrin cathepsin G,  BPI  defensins, HMG1/2, catalase etc. Methodological update ANCA.mht
  8. 8. Methodological update ANCA.mht
  9. 9.  It is poorly understood how ANCA are developed. Two possible mechanisms of ANCA development are postulated:  Theory of molecular mimicry.  Theory of defective apoptosis. Methodological update ANCA.mht
  10. 10.  Theory of molecular mimicry.  Theory of defective apoptosis.  Superantigens have the  ANCA may be developed power to stimulate a strong either via ineffective immune response . THEY apoptosis or ineffective have regions that resemble removal of apoptotic cell self-antigens – this is the fragments, leading to the theory of molecular mimicry. exposure of the immune system to molecules  classical example in post normally sequestered inside group A streptococcal the cells. This theory solves rheumatic heart the paradox of how it could disease, where there is be possible for antibodies to similarity between M be raised against the proteins of Streptococcus intracellular antigenic pyogenes to cardiac myosin targets of ANCA.[4] and laminin. Methodological update ANCA.mht
  11. 11. p-ANCA, show a perinuclear staining patternc-ANCAs, show a diffusely granular,cytoplasmic staining patternAtypical that develop against antigens other than MPO orPR3 will occasionally result in patchy staining Methodological update ANCA.mht
  12. 12. cANCA disease : pANCA disease association: Atypical association• Primary vasculitis • Primary vasculitis • Primary Microscopic polyangitis sclerosing Churg-Strauss syndrome • Wegeners cholangitis Polyarteritis nodosa granulomatosis • Primary biliary• Collagenosis • Microscopic cirrhosis Feltys syndrome polyangitis SLE • Autoimmune Rheumatiod arthritis • Churg-Strauss hepatitis Sjögrens syndrome syndrome. • SLE• Chronic inflammatory bowel disease • RA• Chronic liver disease Primary sclerosing cholangitis Methodological update ANCA.mht
  13. 13. Definition Wegeners granulomatosis is a uncommon type of (vasculitis). It classically involves the lungs, the nasal passages (sinuses), and the kidneys. Nasal or oral inflammation:Clinical Lungs: abnormal chest X-ray .Picture Kidneys: with microhematuria or red cell casts Biopsy: granulomatous inflammation Initial treatment is corticosteroids and oral CYC. On remission treatment is changed to azathioprineTreatment or methotrexate. Duration of therapy should be at least one year.
  14. 14. • Renal GN 79%.Definition Features Treatment • daily/ • May progress to irreversible rapid intermittent progressive renal I.v • Microscopic damage If not cyclophosph polyangiitis treated . amide 6- (MPA) is • Weight loss 12months . vasculitis of 73%. small vessels. • Methotraxat • Fever 55%. e or • Pulmonary: azathioprine alveolar in remission stage of the hemorrhage. disease. Methodological update ANCA.mht
  15. 15. Definition Features Treatment • Treatment is • 1. A prodromal prednisone for mild• An eosinophil- phase cases , systemic rich form of • Allergic disease. involvement granulomatous cyclophosphamide inflammation • 2. Eosinophilia- to be added. mainly tissue infiltration involving phase: • Clinical remission • Eosinophilia. seen in 90% of the respiratory tract cases and • 3. Vasculitic phase : recurrences seen in• Asthma and 25% • Systemic eosinophilia. necrotizing vasculitis . Methodological update ANCA.mht
  16. 16.  The application of ANCA useful in both the diagnosis and monitoring of disease activity . Applications of Antineutrophil Cytoplasmic Antibody.mht
  17. 17. Microscopic Wegeners Churg- Polyangiitis Granuloma StraussANCA tosis SyndromePR3-ANCA 40 80% 10%MPO-ANCA 50% 20% 60%Negative 10% 5% 30% Methodological update ANCA.mht
  18. 18. Prevalence of ANCA in renal vasculitis Type of renal ANCA test positivity (%) vasculitis P-ANCA C-ANCA Polyarteritis nodosa 10-20% 10-20% Microscopic polyangitis 50-80% 10-20%Wegener`s granulomatosis 10-20% 80-90%Necrotizing and crescentic 50-80% 10-20% GN Clinical immunology principles and practice RICH, 2nd edition
  19. 19.  In Juvenile rheumatoid arthritis :  Occur in 10-20% of active conditions.  Showing atypical pattern.  Does not correlate with clinical parameters. Clinical immunology principles and practice RICH, 2nd edition pr
  20. 20.  Autoimmune hepatitis :  Showing p-ANCA pattern.  Seen in 65%-96% in AIH-1 not in AIH-2.  Not correlated with disease activity and liver function test. Clinical immunology principles and practice RICH, 2nd edition pr
  21. 21.  Inflammatory bowel disease:  Showing p-ANCA pattern more seen in UC than CD.  Not been used for distinguishing the 2 diseases . Clinical immunology principles and practice RICH, 2nd edition pr
  22. 22.  Drug-induced ANCA:  Picture of ANCA-associated vasculitis (AAV).  Propylthiouracil is a well-documented cause of drug- induced AAV.  Other drugs: ▪ Hydralazine,sulfasalazine. ▪ minocycline, D-penicillamine. ▪ ciprofloxacin, phenytoin. ▪ clozapine, allopurinol, and pantoprazole. AccessMedicine - ANCA induced by drugs.mht
  23. 23.  Usually of p-ANCA pattern. Slow resolving condition. Good responding to low dose of immunosuppressive agents. AccessMedicine - ANCA induced by drugs.mht
  24. 24.  Prognostic significance of ANCAs:  Increasing ANCA titers do not reliably predict relapse.  Nevertheless, many clinicians assume that ANCA titers are reliable indicators of disease activity !. ANCAClinical Applications of Antineutrophil Cytoplasmic Antibody.mht
  25. 25.