A Population-based Study Showing Better Renal Prognosis for Proteinase 3 Antineutrophil Cytoplasmic Antibody (ANCA)–associated Nephritis Versus Myeloperoxidase ANCA–associated Nephritis

2014 ◽  
Vol 41 (7) ◽  
pp. 1366-1373 ◽  
Author(s):  
Aladdin J. Mohammad ◽  
Mårten Segelmark

Objective.Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is usually differentiated based on clinical phenotypes, but recent data indicate that myeloperoxidase (MPO)-AAV is genetically distinct from proteinase 3 (PR3)-AAV. We reviewed a population-based cohort of AAV, focusing on differences in clinical and laboratory characteristics and to compare renal outcome between MPO-ANCA and PR3-ANCA nephritis.Methods.All new cases of AAV diagnosed between 1997 and 2009 in a geographically defined area in southern Sweden were retrieved using a validated search algorithm. Data were collected from time of diagnosis and end of followup. Renal and patient survival were analyzed according to ANCA serotype.Results.During the study period, 201 patients were diagnosed with AAV, 98 tested positive for PR3-ANCA, and 85 for MPO-ANCA. Patients with PR3-ANCA were younger, had significantly higher inflammatory activity, and had a larger number of organs involved at diagnosis, but nephritis was more prevalent among patients with MPO-associated (72/85; 85%) versus PR3-associated disease (67/98, 68%). When comparing only patients with ANCA-associated nephritis, those with MPO-ANCA were more likely to develop endstage renal disease (n = 27, 38%) than those with PR3-ANCA (n = 10, 15%), p = 0.003. The risk remained significantly elevated after adjusting for sex, age, and s-creatinine level at diagnosis (HR 2.64; 95% CI 1.25–5.58; p = 0.003). There were no significant differences in mortality rates between the 2 groups.Conclusion.The outcome in this population-based cohort indicates that among AAV patients with nephritis, renal prognosis is better in the PR3-ANCA group, even after adjustment for sex, age, and renal function at diagnosis.

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2822-2827 ◽  
Author(s):  
Christoph Hess ◽  
Salima Sadallah ◽  
Jürg-Alfred Schifferli

Abstract Antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) are the predominant autoantibodies present in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Their binding to the corresponding antigen on the surface of polymorphonuclear neutrophils (PMNs) is believed to trigger the disease process. Cytokines released during an inflammatory reaction are thought to prime resting PMNs, making them responsive to autoantibodies. In the present study we found that MPO but not PR3 could be detected on the cell surface of unstimulated PMNs after incubation with the supernatants of activated autologous PMNs. MPO was shown to be acquired from these supernatants, because PMNs did not express MPO when the supernatants were specifically MPO-depleted. In addition, purified soluble MPO bound to unstimulated PMNs. Unstimulated PMNs that had passively acquired MPO released oxygen radicals when incubated with monoclonal antibody anti-MPO or the immunoglobulin G fraction of a patient with MPO-ANCA. The data presented here suggest that, in ANCA-associated vasculitis, soluble MPO released by activated PMNs may bind to unstimulated PMNs, thereby making them reactive to anti-MPO antibodies. This mechanism of dispersing PMN activation would be specific for MPO-ANCA and may explain differences in the pathologic and clinical expression of MPO-ANCA versus PR3-ANCA vasculitis.


Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2822-2827 ◽  
Author(s):  
Christoph Hess ◽  
Salima Sadallah ◽  
Jürg-Alfred Schifferli

Antibodies against myeloperoxidase (MPO) and proteinase 3 (PR3) are the predominant autoantibodies present in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Their binding to the corresponding antigen on the surface of polymorphonuclear neutrophils (PMNs) is believed to trigger the disease process. Cytokines released during an inflammatory reaction are thought to prime resting PMNs, making them responsive to autoantibodies. In the present study we found that MPO but not PR3 could be detected on the cell surface of unstimulated PMNs after incubation with the supernatants of activated autologous PMNs. MPO was shown to be acquired from these supernatants, because PMNs did not express MPO when the supernatants were specifically MPO-depleted. In addition, purified soluble MPO bound to unstimulated PMNs. Unstimulated PMNs that had passively acquired MPO released oxygen radicals when incubated with monoclonal antibody anti-MPO or the immunoglobulin G fraction of a patient with MPO-ANCA. The data presented here suggest that, in ANCA-associated vasculitis, soluble MPO released by activated PMNs may bind to unstimulated PMNs, thereby making them reactive to anti-MPO antibodies. This mechanism of dispersing PMN activation would be specific for MPO-ANCA and may explain differences in the pathologic and clinical expression of MPO-ANCA versus PR3-ANCA vasculitis.


2014 ◽  
Vol 146 (4) ◽  
pp. 950-960 ◽  
Author(s):  
N. Jewel Samadder ◽  
Karen Curtin ◽  
Thérèse M.F. Tuohy ◽  
Lisa Pappas ◽  
Ken Boucher ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Richard A. Lau ◽  
Ramandeep Bains ◽  
Duminda Suraweera ◽  
Jane Ma ◽  
Emil R. Heinze ◽  
...  

This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases.


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