The Ultimate Rheumatology Information Sharing Source
In 2010, EuroDiagnostica is establishing an ongoing interactive dialogue focused on increasing education and the advancement of early diagnosis of RA, autoimmune and rheumatological disorders.
We are looking to kickoff this initiative, with webinars and ongoing blogs featuring individuals who are well recognized in the fields such as Walther J. van Venrooij (Inventor of CCP Assay) and Dr. Jorgen Wieslander (Founder of Wieslab & Pioneer in the Creation of Modern Diagnostic ANCA) and others. Additionally we are seeking your thoughts on topics and focus for 2010.
Please suggest the best times and days of the week for these webinars and we will add your name to our expanding invite list. Also your comments and questions are encouraged and welcome here.
December 18, 2009 at 11:46 am
Diagnosis of reno-pulmonary syndromes.
Jörgen Wieslander, Technical Director, Euro-Diagnostica AB
In 1919 Ernest W. Goodpasture described the association of kidney and lung involvement in patients during the big influenza epidemic. In1967 it was shown that the disease can be transferred with the autoantibody to the glomerular basement membrane (GBM) and then it was realized that autoantibodies could play a role in the pathogenesis. In 1985 another antibody was identified; the so called ANCA (antineutrophil cytopplasmic antibodies). It is now known that most patients presenting with RPS have one of three autoantibodies; the anti-GBM antibody, PR3-ANCA and MPO-ANCA.
The most severe cases with rapidly progressing glomerulonephritis have the anti-GBM antibody and it is usually called Goodpasture Syndrome or Goodpasture disease. The antibodies are directed to the GBM (as well as the lung basement membrane). A structure involved in the filtering of urine. One of the major proteins of the GBM is type IV collagen and the epitope of the autoantibodies is located on the NC1 domain of the alpha 3 chain. When these antibodies are found in a patient it is important to start therapy at once to remove the toxic antibodies. The therapy is plasma exchange and immunosuppressive drugs. About 1/3 of the patients also have ANCA.
The ANCA produce a cytoplasmic (C-ANCA) or perinuclear (P-ANCA) staining on ethanol fixed neutrophils. Early on it was found that C-ANCA most of the time reacted with proteinase 3 (PR3-ANCA) and P-ANCA with myeloperoxidase (MPO-ANCA) . PR3 is a neutral serine protease while MPO is the green colour of pus and kills bacteria by generating oxygen radicals. Many methods exist to detect these antibodies but comparison is difficult due to the lack of standardisation. Recently an International standard have been made available and thus in the future it should be easier to compare methods. PR3-ANCA and MPO-ANCA occur in patients with systemic vasculitis and PR3-ANCA more in Wegeners granulomatosis while MPO-ANCA more in patients with Microscopic polyangiitis, but the overlap is large.
It is advisable to always test for the three antibodies in patients presenting with rapidly progressive disease with renal involvement.
Take home messages:
1. Three autoantibodies are of importance in RPS; anti-GBM, PR3-ANCA, MPO-ANCA.
2. The anti-GBM epitope is hidden in the alpha 3 chain of type IV collagen.
3. Proteinase 3 and Myeloperoxidase are the major antigens in systemic vasculitis.