Epitope shift of proteinase-3 anti-neutrophil cytoplasmic antibodies in patients with small vessel vasculitis.

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T1 - Epitope shift of proteinase-3 anti-neutrophil cytoplasmic antibodies in patients with small vessel vasculitis.

AU - Selga, Daina

AU - Segelmark, Mårten

AU - Gunnarsson, Lena

AU - Hellmark, Thomas

PY - 2010

Y1 - 2010

N2 - Summary Anti-neutrophil cytoplasmic antibodies against proteinase 3 (PR3-ANCA) are used as diagnostic tools for patients with small vessel vasculitis (AASV). We have produced chimeric mouse/human PR3 molecules and investigate changes in reactivity over time and the possible relationship between epitope specificity and clinical course. Thirty-eight PR3-ANCA-positive patients diagnosed between 1990 and 2003 were followed until December 2005. Plasma was collected at each out-patient visit and older samples were retrieved retrospectively. Patients reacted with multiple epitopes at the time of diagnosis. At subsequent relapses 12 patients shifted reactivity, in 11 cases from epitopes located in the C-terminal towards epitopes in the N-terminal. Patients with reactivity against N-terminal parts of PR3 at diagnosis had a significantly lower relapse rate, 30% compared to 78% in the group with predominantly C-terminal reactivity (P = 0.04). The reactivity pattern did not correlate to outcome measured as death, end-stage renal disease or vasculitis activity index score (VDI) at 5 years. Further research is necessary to conclude if this is a general phenomenon.

AB - Summary Anti-neutrophil cytoplasmic antibodies against proteinase 3 (PR3-ANCA) are used as diagnostic tools for patients with small vessel vasculitis (AASV). We have produced chimeric mouse/human PR3 molecules and investigate changes in reactivity over time and the possible relationship between epitope specificity and clinical course. Thirty-eight PR3-ANCA-positive patients diagnosed between 1990 and 2003 were followed until December 2005. Plasma was collected at each out-patient visit and older samples were retrieved retrospectively. Patients reacted with multiple epitopes at the time of diagnosis. At subsequent relapses 12 patients shifted reactivity, in 11 cases from epitopes located in the C-terminal towards epitopes in the N-terminal. Patients with reactivity against N-terminal parts of PR3 at diagnosis had a significantly lower relapse rate, 30% compared to 78% in the group with predominantly C-terminal reactivity (P = 0.04). The reactivity pattern did not correlate to outcome measured as death, end-stage renal disease or vasculitis activity index score (VDI) at 5 years. Further research is necessary to conclude if this is a general phenomenon.

U2 - 10.1111/j.1365-2249.2009.04063.x

DO - 10.1111/j.1365-2249.2009.04063.x

M3 - Article

VL - 160

SP - 318

EP - 324

JO - Clinical and Experimental Immunology

JF - Clinical and Experimental Immunology

SN - 0009-9104

ER -