De Pellegrin, Annamaria (2008) Role of ANCA in necrotizing vasculitis and in chronic inflammatory
intestinal disease. [Ph.D. thesis]
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Background: Wegener's granulomatosis (WG), Microscopic Poliangitis and Churg-Strauss Syndrome, the necrotizing vasculitis, are a group of inflammatory diseases of the
wall small-medium calibre blood vessels. This group of diseases are hystologically characterized by the presence of necrotic tissue with a consequent inflammatory infiltration and the formation of granulomas. GW is a disease which has periods of
remission and recurrence treated by therapeutic cycles associated with several side-effects. It is caracterized by the presence in serum of anti-neutrophil cytoplasm antibodies (ANCA). ANCA are auto-antibodies against enzymatic antigens
found in primary granules of neutrophyls and in peroxydase-positive lysosomes of monocytes.The two main antigens are serin proteinase-3 (PR3), a cytoplasmatic
protein and leucocyte myeloperoxydase (MPO). Indirect immunofluorescence permits to differentiate two distinct patterns, cytoplasmic (c-ANCA) and perinuclear (p-ANCA),
according to the involved antigen, accordingly PR3 and MPO.
Both patterns of ANCA presentation, mainly p-ANCA, are found in chronic inflammatory intestinal disease (IBD), noticeably Crohn's disease (CD) and ulcerative colitis (UC).
Study goal: To evaluate the prevalence of ANCA in a population of patients with WG and one with CIID. In these two groups we studied: presentation pattern, correlation among antibody titer, clinical phase and disease localization; the role of infective
agents as factors initiating ANCA production. Finally we correlated ANCA titers with response to treatment and disease complications. Patients and methods: we studied 13 patients with WG, some of which we had treated for over 7 years. In all patients ANCA levels were titred at the moment of diagnosis
and during recurrences. Cultures were performed during episdoes of infectious disease. 37 patients with IBD admitted to a general surgical department for colic resection or for treatment of anal abscesses or fistulas were also studied, of these 12 had UC and 15 CD. Patients were studied in 2 different stages: preoperatively and 3 months after surgery. We evalutated:ANCA dosage, erythrocyte sedimentation rate, CRP, fibrinogen levels, direct or anamnestic determination of infectious episodes. Serum ANCA levels were dosed according to indirect immunofluorescence and, if positive, their presence was confirmed by ELISA.
Results: ANCA were useful, if not decisive, in 85% of patients with WG, with titers ranging from 1:160 to 1:280. c-ANCA were 100% specific in patients with WG. ANCAs reappeared during follow-up in only 3 patients . Infectious episodes seemed to have been the factor causing recurrence. The presence of Staphylococcus aureus seems to favor the reappearance of ANCA in patients with WG while bactertial and/or viral infections may be responsible for ANCA-negative. p-ANCA were detected in 83% of patients with CU and in only 20% of patients with MC before surgery. After surgical treatment, ANCA were detected in 75% of patients with CU, while remain 20% in MC patients, but with lower titer.
Conclusions: also our study demonstrates to the usefulness of the search and dosage of the ANCA in the diagnosis and follow-up of the GW. P-ANCA had a clean prevalence
in the UC but they aren't useful in other chronic diseases. Also not playing a determining role in the diagnosis and not predicting in the prognosis of the IBD, ANCA turns out from our study a useful additional test in the diagnostic one
differentiates them between UC and MC.
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