Table 3.
Similarities and differences between PR3-AAV and MPO-AAV with quality of evidence
| Feature | Evidence | PR3-AAV | MPO-AAV |
|---|---|---|---|
| Epidemiology | |||
| ♂/♀ ratio | B | Higher | Lower |
| Geographical distribution | A | More prevalent in northwestern Europe and North America | More prevalent in southern Europe, Asia and the Pacific |
| Incidence 11.3/million/yr in UK and 3/million/yr in Spain | Incidence 5.9/million/yr in UK and 7.9/million/yr in Spain | ||
| Genetics | |||
| HLA-DPB1 | A | More prevalent | Less prevalent |
| HLA-DQ | B | Less prevalent | More prevalent |
| PRTN3 | B | More prevalent | Less prevalent |
| CTLA-4 | C | Less prevalent | More prevalent |
| HLA-DRB*15 | C | More prevalent in African Americans | Not prevalent |
| Renal histopathology | C | In both serotypes granuloma formation can be seen | |
| Normal glomeruli | A | More | Less |
| Fibrosis | C | Less | More |
| Electron-dense deposits | D | Not different | |
| Immunofluorescence | C | Less C3 deposition | More C3 deposition |
| Clinical presentation | |||
| Age at onset | A | Not different | |
| Organ involvement in general | B | More ear, nose, and throat involvement | More renal-limited |
| Pulmonary | C | Cavitating lesions | Fibrosing lesions |
| Alveolar lung hemorrhage | C | More | Less |
| Ear, nose, and throat | B | Necrotizing lesions | Polyps |
| Nervous system | C | Similar frequency | |
| Skin | C | Not different | |
| Cardiac | C | Not different | |
| Ophthalmologic | C | More ophthalmologic involvement | Less ophthalmologic involvement |
| Follow-up | |||
| Relapse rate | A | Higher | Lower |
| Patient survival | C | Similar/better | Similar/worse |
| Renal survival | C | Similar/better | Similar/worse |
| Infection | D | Not different | |
| Cardiovascular | C | Fewer events | More events |
| Venous thromboembolism | D | Not different | |
| Malignancies | D | Not different | |
| Treatment | C | Not different | |
| Etiology | C | S. aureusa | Silica associateda |
| Low vitamin D levelsa | |||
| Pathophysiology | |||
| In vitro interaction of ANCA with neutrophils | D | Not different | |
| Endothelial cells | D | PR3 induces apoptosis of endothelial cell | MPO induces production of intracellular oxidants |
| Monocytes | D | PR3-ANCA induces release of sFlt1 by monocytes | MPO-ANCA does not induce release of sFlt1 |
| In vivo animal models | D | Less successful models, possibly due to different interaction of PR3 with NB1 in mice | Successful mouse and rat models resulting in vasculitis and necrotizing crescentic GN |
Quality of evidence was based on the GRADE system as follows: A, Further research is very unlikely to change our confidence in the estimate of effect; B, Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate; C, Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate; D, Any estimate of effect is very uncertain). GRADE, Grading of Recommendations Assessment, Development and Evaluation.
a
These etiologic factors remain speculative due to insufficient evidence.