Latent class analysis of chest CT abnormalities to define subphenotypes in patients with MPO-ANCA-positive microscopic polyangiitis.

BACKGROUND: Patients with microscopic polyangiitis (MPA) and positive myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) may present with various abnormalities in chest computed tomography (CT). This study aimed to identify subphenotypes using latent class analysis (LCA) and to explore the relationship between the subphenotypes and clinical patterns, as well as compare the clinical characteristics of these subphenotypes in patients with MPO-ANCA-positive MPA (MPO-MPA). METHODS: The study identified subphenotypes using LCA based on chest CT findings in 178 patients with MPO-MPA and pulmonary involvement from June 2014 to August 2022. RESULTS: LCA identified 27 participants (15.2%) in class 1, 43 (24.1%) in class 2, 35 (19.7%) in class 3, and 73 (41.0%) in class 4. Class 1 was characterized by prominent inflammatory exudation, class 2 by fibrosis and architectural distortion, class 3 by predominantly bronchiectasis, and class 4 by lesions mixed with inflammation and fibrosis. Class 1 had the highest level of extrapulmonary disease activity, with 77.8% of patients experiencing diffuse alveolar hemorrhage. Class 2 had the lowest level of extrapulmonary disease activity, with 41.9% of patients showing usual interstitial pneumonia. Class 3 patients were more likely to have complications involving the ear, nose, and throat, as well as pulmonary infections before treatment, and they exhibited the best outcomes. The characteristics and outcomes of class 4 were intermediate among the four classes. CONCLUSIONS: These findings suggest that bronchiectasis may represent a unique pattern of pulmonary involvement in MPO-MPA, highlighting the importance of screening for bronchiectasis in MPO-MPA and identifying optimal management strategies.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Microscopic Polyangiitis.

OBJECTIVE: To develop and validate classification criteria for microscopic polyangiitis (MPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data-driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (-3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (-1), and eosinophil count ≥1 × 109 /liter (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% confidence interval [95% CI] 85-95%) and the specificity was 94% (95% CI 92-96%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for microscopic polyangiitis.

OBJECTIVE: To develop and validate classification criteria for microscopic polyangiitis (MPA). METHODS: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. RESULTS: The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (-3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (-1) and eosinophil count ≥1×109/L (-4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% CI 85% to 95%) and the specificity was 94% (95% CI 92% to 96%). CONCLUSION: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

The complexity of classifying ANCA-associated small-vessel vasculitis in actual clinical practice: data from a multicenter retrospective survey.

The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3 years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.

Clinical implication of chronic paranasal sinusitis for the classification of microscopic polyangiitis.

BACKGROUND: Chronic paranasal sinusitis (CPS) has been known as a surrogate marker for granulomatosis with polyangiitis (GPA). We investigated whether CPS at diagnosis may have an influence on the classification and outcomes of microscopic polyangiitis (MPA). METHODS: We retrospectively reviewed the medical records of 106 immunosuppressive drug-naïve patients with MPA. We compared variables at diagnosis of MPA patients with CPS with either MPA patients without CPS or 29 GPA patients with CPS. We applied the algorithm for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) proposed by the European Medicine Agency to 22 MPA patients with CPS and reclassify them. Death, relapse and end-stage renal disease were assessed as the poor outcomes. RESULTS: Except for ENT manifestations, only pulmonary manifestation was more frequently observed in MPA patients with CPS than those without (77.3% vs 47.6%). No proteinase 3-ANCA was detected in all MPA patients with CPS. Meanwhile, general (63.6% vs 27.6%) and renal manifestations (81.8% vs 44.8%) more often developed in MPA patients with CPS than GPA patients with CPS. Of 22 MPA patients with CPS, 21 patients underwent biopsies. When CPS was not considered as a surrogate marker for GPA, all patients with CPS were reclassified as MPA. Ground glass opacity and reticulation on high-resolution computed tomography and renal vasculitis were helpful clues supporting the classification of MPA in patients with CPS. CPS at diagnosis was not associated with the outcomes of MPA. CONCLUSION: CPS might not be a sufficient surrogate marker for GPA in the classification of AAV.

Clinical impact of subgrouping ANCA-associated vasculitis according to antibody specificity beyond the clinicopathological classification.

OBJECTIVES: In ANCA-associated vasculitis (AAV), classifications have emerged to individualize homogeneous clinical and outcomes patterns, including the recently defined anti-MPO granulomatosis with polyangiitis (GPA) subgroup. This study aimed to retrospectively evaluate the impacts of re-classification based on clinicopathological criteria and/or ANCA specificity. METHODS: A retrospective monocentric study conducted at Caen University Hospital led to the identification of PR3 or MPO-ANCA AAV patients from January 2000 or September 2011, respectively, to June 2016. Eosinophilic GPA patients were excluded. AAVs were thereby also classified either as GPA or microscopic polyangiitis (MPA) according to the European Medicines Agency vasculitis algorithm. RESULTS: A total of 150 AAV patients were included (94 GPA, 56 MPA; 87 anti-PR3 and 63 anti-MPO patients). GPA patients exhibited a worse relapse-free survival but a better renal survival (P < 0.001 and P = 0.021, respectively) than MPA patients. Overall, relapse-free and renal survival rates were similar between anti-PR3 and anti-MPO patients (P = 0.35, 0.17 and 0.15, respectively). Similarly, the prognosis was identical between anti-MPO MPA patients and anti-PR3 MPA patients (P = 0.33, 0.19 and 0.65, respectively), and between anti-MPO GPA patients and anti-PR3 GPA patients (P = 0.06, 0.99 and 0.64, respectively). Moreover, anti-PR3 GPA and anti-MPO GPA patients exhibited no differences in clinical manifestations or BVAS score. CONCLUSION: Clinicopathological classification appeared to be the strongest criterion for distinguishing among homogeneous prognoses of AAV. Individualizing the anti-MPO GPA subgroup does not appear to bring additional value to clinical practice, but multicentre studies are required to confirm this trend.

The utility of the ACR/EULAR 2017 provisional classification criteria for granulomatosis with polyangiitis in Korean patients with antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVES: We applied the ACR/EULAR 2017 provisional classification criteria for granulomatosis with polyangiitis (GPA) to 150 Korean patients with previously diagnosed antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and investigated how many patients with AAV were reclassified as GPA. METHODS: We included patients with 30 GPA, 30 eosinophilic GPA (EGPA) and 90 microscopic polyangiitis (MPA) patients. Patients can be classified as GPA, when the sum of scores is more than 5. RESULTS: At diagnosis the mean age of 150 patients with AAV was 60.1 years old, and 101 patients (67.3%) were women. Overall, 33 of 150 patients with AAV (22.0%) were classified as GPA according to the 2017 provisional criteria for GPA. The 2017 provisional criteria for GPA dropped to 10.0% of previously diagnosed GPA patients and the major factor to drop 3 GPA patients was the deletion of 2 items of the 1990 criteria, urinary sediment and infiltrates on chest radiograph. Meanwhile, one of 30 patients with EGPA (3.3%) and 5 of 90 patients with MPA (5.6%) were newly classified as GPA based on the 2017 provisional criteria for GPA. We could also find that items of the 2017 provisional criteria to contribute to reclassifying EGPA and MPA patients as GPA were PR3-ANCA, mass-like lung lesion and nasal congestion in Korean patients with AAV. CONCLUSIONS: The use of the 2017 provisional criteria for GPA excluded 10.0% of previously classified GPA patients and newly classified 3.3% of EGPA patients and 5.6% of MPA patients as GPA in Korean patients with AAV.

Different responses to treatment across classified diseases and severities in Japanese patients with microscopic polyangiitis and granulomatosis with polyangiitis: a nationwide prospective inception cohort study.

INTRODUCTION: This study aims to elucidate the prognosis and the effectiveness of current treatments for Japanese patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). METHODS: Patients with newly diagnosed MPA and GPA were enrolled in a nationwide, prospective, inception cohort study from 22 tertiary Japanese institutions, and treatment patterns and responses were evaluated for 24 months. Primary outcome measures were rates of remission (Birmingham Vasculitis Activity Score, 0) and remission with low-dose glucocorticoids (GC) (prednisolone ≤ 10 mg) (GC remission). RESULTS: Of 156 enrolled patients, 78 MPA patients and 33 GPA patients were included. Concomitant cyclophosphamide (CY) was used in 24 MPA (31 %) and 20 GPA (60 %) patients during the initial 3 weeks of treatment. After 6 months, remission was achieved in 66 MPA (85 %) and 29 GPA (87 %) patients, while GC remission was obtained in only 31 MPA (40 %) and 13 GPA (39 %) patients. During the 24-month period, 14 MPA patients and 2 GPA patients died; end stage renal disease (ESRD) was noted in 13 MPA patients but no GPA patients. Patients with severe disease, according to the European Vasculitis Study Group (EUVAS) classification, showed poorer ESRD-free and overall survival rates than those with generalized disease (p < 0.0001). There were no differences in relapse-free survival rates between GPA and MPA, among EUVAS-defined disease severity categories, and between anti-neutrophil cytoplasmic antibody subspecialties. CONCLUSIONS: The majority of Japanese patients with MPA and GPA received treatment with high-dose GC and limited CY use, and showed high remission and relapse-free survival rates but low GC remission rates in clinical practice. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry UMIN000001648 . Registered 28 February 2009.

Current landscape of antineutrophil cytoplasmic antibody-associated vasculitis: classification, diagnosis, and treatment.

This article provides an update on the diagnosis and management of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (formerly Wegener), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss). Focus is on new schemes of classification and the importance of ANCAs in the diagnosis and prognosis of these systemic vasculitides. Current therapeutic strategies consisting of glucocorticoids in conjunction with conventional or biologic agents for both induction of remission and remission maintenance are outlined. Future research directions include investigation of the optimal duration and frequency of maintenance therapy and development of targeted therapeutic agents.

Diagnosis and classification of eosinophilic granulomatosis with polyangiitis (formerly named Churg-Strauss syndrome).

Recently, a group of experts in the field suggested to rename Churg-Strauss syndrome as eosinophilic granulomatosis with polyangiitis (EGPA). This condition, first described in 1951, is a rare small- and medium-sized-vessel vasculitis characterized by an almost constant association with asthma and eosinophilia, and, by the presence of anti-myeloperoxidase (MPO) antineutrophil cytoplasm antibodies (ANCA) in 30-38% of the patients. Vasculitis typically develops in a previously asthmatic and eosinophilic middle-aged patient. Asthma is severe, associated with eosinophilia and extrapulmonary symptoms. Most frequently EGPA involves the peripheral nerves and skin. Other organs, however, may be affected and must be screened for vasculitis, especially those associated with a poorer prognosis, such as the heart, kidney and gastrointestinal tract, as assessed by the recently revised Five-Factor Score (FFS). Recent insights, particularly concerning clinical differences associated with ANCA status, showed that EGPA patients might constitute a heterogeneous group. Thus, EGPA patients with anti-MPO ANCA suffered more, albeit not exclusively, from vasculitis symptoms, such as glomerulonephritis, mononeuritis multiplex and alveolar hemorrhage, whereas ANCA-negative patients more frequently develop heart involvement. This observation led to the hypothesis that EGPA might be divided into different clinical and pathophysiological subtypes, which could be managed better with more specifically adapted therapies. For now, EGPA treatment still relies mainly on corticosteroids and, when necessary for patients with poorer prognoses, combined immunosuppressant drugs, especially cyclophosphamide. Overall survival of EGPA patients is good, despite not uncommon relapses.

The diagnosis and classification of microscopic polyangiitis.

Microscopic Polyangiitis (MPA) is a small vessel vasculitis. The disease is defined by the 2012 revised Chapel Hill Consensus Conference Nomenclature of Vasculitides [1] as necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels (i.e. capillaries, venules, or arterioles). Necrotizing arteritis involving small and medium arteries may be present. Necrotizing glomerulonephritis is very common. Pulmonary capillaritis often occurs. Granulomatous inflammation is absent. MPA belongs to the ANCA-associated vasculitides (AAV). ANCA in MPA are predominantly directed against myeloperoxidase (MPO-ANCA) but may, in a minority of patients, be directed against proteinase 3 (PR3-ANCA). Not all patients, however, have ANCA. Microscopic polyangiitis (MPA) belongs to the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides. MPA is clinically characterized by small-vessel vasculitis primarily affecting the kidneys and the lungs but other organs may be involved as well. Renal involvement, which can be the only manifestation, is clinically apparent as rapidly progressive glomerulonephritis and histopathologically as pauci-immune necrotizing and crescentic glomerulonephritis. ANCA in MPA are mainly directed to myeloperoxidase (MPO-ANCA). Besides their diagnostic significance, MPO-ANCA appear pathogenic in MPA. Rituximab with steroids is at least as effective as cyclophosphamide with steroids for induction of remission.

Validation of the consensus methodology algorithm for the classification of systemic necrotizing vasculitis in Indian patients.

AIM: Many patients with systemic necrotizing vasculitis (SNV) satisfy classification criteria of different disease entities when different classification systems are used. A new classification algorithm has been proposed recently by using the American College of Rheumatology criteria, Chapel Hill Consensus Criteria (CHCC) and Sorensen surrogate markers for a more uniform classification of patients suffering from these rare disorders. METHODS: We applied this algorithm to patients diagnosed as having systemic vasculitis between 2007 and 2011. We also analyzed the data using this algorithm by incorporating the recently proposed revised CHCC nomenclature of vasculitis in place of the older criteria. RESULTS: Seventy-nine patients with SNV were studied. One patient diagnosed as microscopic polyangiitis (MPA) had to be excluded from analysis as she had previously been diagnosed as having Behcet's disease. All patients of eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA) and MPA were reclassified to the same diagnostic subcategory after application of the algorithm. Three (16.7%) of 18 polyarteritis nodosa patients were unclassifiable after application of the consensus algorithm while two (11.1%) were reclassified as MPA. All previously unclassifiable patients could be classified either as MPA or GPA after application of the new algorithm. There was no difference in the results when the CHCC 2012 nomenclature was used instead of the older CHCC in the consensus algorithm. CONCLUSION: The new classification algorithm is a reliable method for classification of SNV for epidemiological purposes in our population.

Uncommon presentations of primary systemic necrotizing vasculitides: the Great Masquerades.

INTRODUCTION: Systemic vasculitides are great masqueraders and at times their presenting manifestations can be very different from the usual recognized patterns. Such uncommon presentations of granulomatosis with polyangiitis (Wegener's granulomatosis), classical polyarteritis nodosa and unclassifiable vasculitides are described here with the relevant review of literature. METHODS: All patients diagnosed as having systemic vasculitides and classified as having granulomatosis with polyangiitis (Wegener's granulomatosis), classic polyarteritis nodosa, microscopic polyangiitis and unclassifiable vasculitis according to EMEA consensus methodology and followed up prospectively from June 2007 to December, 2011 were included. Details of uncommon presentations of these disorders were identified. RESULTS: Seventy-nine patients with systemic vasculitides were seen under our rheumatology services during this period. These included 45 patients with granulomatosis with polyangiitis (Wegener's granulomatosis), 18 with classic polyarteritis nodosa, five with microscopic polyangiitis, four with Churg-Strauss syndrome and seven with unclassifiable vasculitis. The uncommon presentations of granulomatosis with polyangiitis were a tumefactive subcutaneous mass in the thigh; prostatomegaly with obstructive uropathy and advanced renal failure; and predominant gastrointestinal (GI) vasculitis with thrombocytopenia and coagulopathy at presentation. The uncommon manifestations of classic polyarteritis nodosa were secondary antiphospholipid antibody syndrome and Budd-Chiari syndrome. One patient with massive lower GI bleeding required surgical resection of the large bowel which showed isolated necrotizing granulomatous GI vasculitis. Single organ vasculitis of the GI tract was diagnosed. CONCLUSIONS: Systemic necrotizing vasculitides may present with uncommon manifestations and a high index of suspicion is required for early diagnosis and prompt treatment to prevent adverse outcomes.

Classification of ANCA-associated vasculitis.

Classification of the ANCA-associated vasculitides remains controversial. Existing systems, developed by the American College of Rheumatology (ACR) in 1990, the Chapel Hill Consensus Conference (CHCC) in 1994 and updated in 2012, and the European Medicines Agency algorithm, all have deficiencies, especially when applied to unselected patients. The ACR system did not include ANCA or microscopic polyangiitis, and the CHCC (1994) included MPA but not ANCA (this was rectified in the 2012 revision). These systems were developed as classification criteria and not as diagnostic criteria. There are currently no validated diagnostic criteria for AAV. The Diagnostic and Classification Criteria for Vasculitis (DCVAS) study is a global study with the objective of developing and validating diagnostic criteria.

[Vasculitis. New nomenclature of the Chapel Hill consensus conference 2012]. / Vaskulitis. Neue Nomenklatur der Chapel-Hill-Konsensuskonferenz 2012.

In recent years, many advances have been made in our understanding of vasculitis etiopathology as well as of different disease courses. The revised Chapel Hill Consensus Conference (CHCC) 2012 nomenclature reflects current knowledge about etiopathology, in addition to the descriptive principles of vessel size and type of inflammation. Anti-neutrophil cyptoplasmic antibody (ANCA)-associated vasculitides have been classified as a separate group, as opposed to immune complex small vessel vasculitis. In cases where consensus was achieved, eponyms have been replaced by systematic names, such as granulomatosis with polyangiitis (Wegener's) or eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome). Moreover, clinically important but less well-known types of vasculitis have now been included in the CHCC nomenclature. This article presents the changes, focussing on those types that are relevant to the histopathologist, and summarizes the results of important new articles on morphology and clinical picture of vasculitis.

Comparative proteomic analysis of neutrophils from patients with microscopic polyangiitis and granulomatosis with polyangiitis.

Both microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) belong to ANCA-associated vasculitis (AAV), in which neutrophils play a key role in their pathology. In this study, in order to discriminate between MPA and GPA, protein profiles of peripheral blood polymorphonuclear cells (PMNs) of 11 MPA patients and 9 GPA patients and 10 healthy controls (HC) were analyzed by 2D-DIGE. In all the 864 spots detected, intensity of 55 spots was significantly different (p<0.05) among the three groups by ANOVA. 31 out of the 55 spots were identified by mass spectrometry. Orthogonal partial-least-squares-discriminate analysis revealed that the abundance profile of the protein spots discriminated the AAV group from the HC group, and the MPA group from the GPA group completely. 13 protein spots were considered as biomarker candidates to distinguish between MPA and GPA. In those, spots whose intensity was higher in MPA than in GPA included actin with various pI values, while a considerable part of spots whose intensity was higher in GPA were proteins related with the activity of neutrophils. Among the candidate proteins, ROC analysis showed that a combination of neutrophil gelatinase-associated lipocalin and a-kinase anchor protein 7 isoforms beta had a high diagnostic potential. BIOLOGICAL SIGNIFICANCE: In this study, protein profiles of polymorphonuclear cells (PMNs) of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients and healthy controls (HC) were investigated by 2D-DIGE, and MS analysis. As a result, we found that the protein profiles of PMNs were useful for distinguishing between patients (MPA and GPA) and HC, and between patients with MPA and patients with GPA. Especially, we found that the 13 protein spots that consisted of 10 proteins considerably contributed to the discrimination between MPA and GPA. This is the first to demonstrate that protein profiles of PMNs are different among MPA, GPA and healthy control. The 10 proteins we identified in this study would be new biomarkers for the diagnosis of the diseases, and may be reflect the pathology difference between MPA and GPA.

Antineutrophil cytoplasmic antibody-associated vasculitides: is it time to split up the group?

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a heterogeneous group of diseases corresponding to necrotising inflammation of small vessels with a wide range of clinical presentations. At least two of the diseases are believed to exhibit a common ground of pathophysiological mechanisms. These are granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis) and microscopic polyangiitis (MPA). ANCA directed against proteinase 3 (PR3) are preferentially associated with GPA, and anti-myeloperoxidase (MPO) ANCA are associated mainly with MPA and eosinophilic GPA (formerly known as Churg-Strauss syndrome). Anti-MPO and anti-PR3 antibodies can activate neutrophils in vitro. In vivo data are available for humans and mice on the pathogenicity of anti-MPO but it is more controversial for PR3-ANCA. A recent genome-wide association study of patients with ANCA-associated vasculitides confirmed the genetic contribution to the pathogenesis of these conditions, with significant association of PR3-ANCA and human leukocyte antigen-DP and the genes encoding α1-antitrypsin and PR3. MPO-ANCA were significantly associated with human leukocyte antigen-DQ. Thus, recent results from epidemiological studies, genome-wide association study and therapeutic trials have suggested that these entities are, in fact, distinct. We have summarised these results and discuss the idea that these two entities should be studied separately as the nature of the two auto-antigens suggests at a molecular level despite shared ANCA involvement.