Different Types of ANCA Determine Different Clinical Phenotypes and Outcome in ANCA-Associated Vasculitis (AAV)

Abstract

AimAccumulating evidence supports the use of antineutrophil cytoplasmic antibody (ANCA) type to classify different clinical entities. We aimed to evaluate whether the presence and type of ANCA determine different diseases, based on clinical phenotypes, renal involvement, and response to treatment.Patients and MethodsDifferences in terms of clinical manifestations, disease activity, laboratory parameters, and histology were recorded between patients with focal necrotizing glomerulonephritis (FNGN) due to myeloperoxidase (MPO-), proteinase 3-ANCA(+) [PR3-ANCA(+)], and ANCA(-) disease at time of diagnosis. Patients were treated with the same protocol and followed-up for 24 months, in a scheduled basis of every month for the first year and every 3 months for the second year. Primary end points were: (i) Combined end-stage renal disease (ESRD) and/or death and (ii) The presence of major or minor relapse during follow-up and secondary endpoint was the combination of ESRD and reduction of estimated glomerular filtration rate (eGFR) ≥ 50%.ResultsA total of 92 patients (M/F 39/53, mean age 59.1 ± 15 years) diagnosed with FNGN due to ANCA-associated vasculitis (AAV), 36 (39.1%) patients diagnosed with PR3-ANCA, 39 (42.4%) patients diagnosed with MPO-ANCA, and 17 (18.5%) patients diagnosed with ANCA(-) were included. Number of involved systems differed significantly between PR3-, MPO-ANCA, and ANCA(-), with only renal involvement in 3, 25.5, and 29% of patients, two systems involved in 33, 31, and 59% of patients, and > 3 systems involved in 64, 43.5, and 12% of patients, respectively (p = 0.002). Histology classification revealed focal, crescentic, mixed, and sclerotic type in 14, 64, 19, and 3% of PR3-ANCA(+), 8, 28, 18, and 46% of MPO-ANCA, and 41, 29, 6, and 24% of ANCA(-), respectively (p < 0.0001). Primary end point of ESRD ± Death was reached in 11 (30.6%), 16 (41%), and 6 (35.5%) patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), respectively (p = NS); similarly, ESRD± > 50% eGFR reduction in 8 (22.2%), 15 (38.5%), and 5 (29.4%) patients, respectively (p = NS), meaning that patients with MPO-ANCA(+) showed a propensity to decline renal function. Rate of relapse was increased in the presence of patients with PR3-ANCA(+), 14 (38.9%), 4 (11.8%), and 2 (10.3%) of patients with PR3-ANCA(+), MPO-ANCA(+), and ANCA(-), had at least one relapse during the two-year follow-up (p = 0.006).ConclusionClinical phenotype and renal histology differ significantly between PR3-ANCA(+), MPO-ANCA(+), and ANCA(-) disease and FNGN; however, renal function outcome is similar, despite the increased rate of relapses in patients with PR3-ANCA(+).

Validation of a renal risk score in a cohort of children with ANCA-associated glomerulonephritis

“…Researchers suggested that the use of ANCA specificity rather than the use of clinical syndromes, to categorize the AAVs, 28,29 because MPO-AAGN and PR3-AAGN showed differences in clinical phenotype and renal histology. 30 In our cohort, the proportion of patients with normal glomeruli >25% (68.85%) was similar to the results of Saito et al, 14 and the proportion of patients with IFTA ≤ 25% (60.66%) was similar to the results of An et al, 26 with a high positivity rate for MPO-ANCA. However, the results of Mejia-Vilet et al showed the proportion of patients with IFTA > 25% with the lowest MPO-ANCA positivity was similar to our results (39.34%).…”

Type of ANCA May Be Indispensable in Distinguishing Subphenotypes of Different Clinical Entities in ANCA-Associated Vasculitis

“…ANCA(−) vasculitis also shows a higher percentage of sclerotic lesions and interstitial fibrosis, similar to the damages found in MPO-ANCA vasculitis [ 56 ]. A recent study that evaluated the association between ANCA specificity and histopathology findings revealed that 64% of PR3-ANCA patients had the crescentic phenotype and only 3% the sclerotic one [ 57 ]. On the other hand, renal histology in MPO-ANCA and ANCA(−) patients was similar, with only 28% having the crescentic and 46% the sclerotic phenotype.…”