ANCA-positive Group Research Articles

The uncertain correlation of ANCAs in patients with lupus nephritis and crescents, an experience from Chinese centers.

The precise role of anti-neutrophil cytoplasmic antibodies (ANCAs) in the pathologic course of crescentic lupus nephritis (LN) remains unclear. Our study aimed to assess whether ANCA-positive serology in patients with LN and crescents is associated with different clinicopathologic features and outcomes. We reviewed the records of 658 patients diagnosed with LN between 2010 and 2022. Among them, 64 (9.7%) patients who had complete follow-up and clinical data were reclassified as crescentic glomerulonephritis. Of these, 11 patients with incomplete ANCA data and 7 patients with less than 10 glomeruli under light microscopy were excluded; ultimately, 46 patients were enrolled: 12 with ANCA positivity and 34 with ANCA negativity. Clinicopathological characteristics and outcomes were analysed and compared. Our data did not reveal any differences in clinical or laboratory parameters or histopathological features except for a significantly higher level of proteinuria or proportion of nephrotic syndrome (p < 0.05) at presentation before biopsy in the ANCA-negative group than in the ANCA-positive group,and a lower level of serum albumin (p < 0.05) in the ANCA-negative group than in the ANCA-positive group. No significant differences in complete remission or partial response were detected between the two groups based on the 2021 KDIGO criterion. Short-term follow-up (average follow-up time of less than 3 years) did not reveal any difference in outcomes between ANCA-positive and ANCA-negative crescentic LN. However, the role of ANCAs in the pathological course of crescentic lupus nephropathy and the effect of ANCAs on long-term outcomes remain to be determined.

Clinicopathological characteristics and renal outcomes of adult patients with pauci-immune necrotizing glomerulonephritis according to ANCA status.

Pauci-immune necrotizing glomerulonephritis (PING) is commonly associated with the presence of antineutrophilic cytoplasmic antibodies (ANCAs) but a significant number of patients do not have these antibodies. The significance of ANCA-negativity in the context of Berden's classification of PING is not known. A retrospective analysis was conducted on all patients with histopathological diagnosis of idiopathic PING irrespective of ANCA status diagnosed between January 1998 to December 2018 and followed up at renal clinic for > 12months. All biopsies were reclassified by Berden's classification. Clinicopathological characteristics and renal outcomes of ANCA-positive and ANCA-negative patients were compared. Out of 134 patients, 66 (49.5%) were ANCA-negative. The mean age was 34.76 ± 13.3years. Compared with the ANCA-positive patients, ANCA-negative patients had significantly greater prevalence of nephrotic-range proteinuria (74.23% Vs 57.9%, P = 0.036) with less extra-renal manifestations (P < 0.05)). On histology, focal and crescentic classes dominated with less number of globally sclerosed glomeruli (2.7% Vs 5.07%, P = 0.02) and more mesangial proliferation (22.7% Vs 4.41%, P = 0.002) in the ANCA-negative group, whereas sclerotic was predominant in the ANCA-positive group (P = 0.05). More patients achieved complete and partial recovery in ANCA-negative patients (42.4% Vs 20.5%, P < 0.05) with better renal survival (27.27% Vs 16.17%, log-rank test: P = 0.03) and less patient mortality (13.63% vs 30.8%, log-rank test: P = 0.04) at 2years. Our study confirms high prevalence of ANCA negativity among our cohort and this group presents with isolated renal involvement with better renal and patient survival. The ANCA-positive group showed significantly more patients in the sclerotic class, lower 2-year renal survival, and higher 2-year mortality as compared to the ANCA-negative group. However, the complete and partial responses to treatment were significantly better in the ANCA-negative group. Key Points • This study shows a high prevalence of ANCA negativity in cases of PING in Pakistani population, as almost half of patients in this study did not have these antibodies. • This negativity is more prevalent in the Asian populations but its significance in the context of Berden's classification of PING is unknown. • ANCA-negative group exhibited less severe phenotype and better outcomes compared with ANCA-positive group.

Anti-Citrullinated Peptide Antibody Expression and Its Association with Clinical Features and Outcomes in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Background and objectives: Anti-citrullinated peptide antibody (ACPA), a characteristic antibody detected in rheumatoid arthritis, could be linked to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) via the formation of neutrophil extracellular traps. We investigated the rate of ACPA positivity in patients with AAV and evaluated the association of ACPAs with their clinical features and outcomes. Materials and Methods: A total of 168 AAV patients with both ACPA and ANCA results at diagnosis were identified. Clinical and laboratory variables, including the disease-specific indices of Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS), were investigated. All-cause mortality, relapse, and end-stage renal disease, as well as interstitial lung disease (ILD) were evaluated as outcomes of the patients, and the Kaplan–Meier survival analysis was used to compare the event-free survival rates of the groups. Results: Fifteen (8.9%) and 135 (80.4%) patients were positive for ACPA and ANCA, respectively. There were no significant differences in the baseline variables of ACPA-negative and ACPA-positive patients. The absolute titre of ACPAs also did not significantly correlate with BVAS, FFS, erythrocyte sedimentation rate, or C-reactive protein. In addition, there was no difference noted regarding overall, relapse-free, and ESRD-free survival rates between ACPA-negative and ACPA-positive AAV patients. However, when the patients were divided into four groups according to ACPA and ANCA status, differences were present in the outcomes, and the ACPA-positive ANCA-positive group exhibited the lowest cumulative relapse-free survival rate, while no significant difference was present in the relapse between the ANCA-positive ANCA-positive, ACPA-positive ANCA-negative, and ACPA-negative ANCA-positive groups. Finally, the cumulative ILD-free survival rates were comparable between ACPA-positive and ACPA-negative AAV patients. Conclusions: The detection of ACPA expression is not uncommon in AAV. However, the presence of ACPA did not influence patients’ basal characteristics and outcomes, suggesting that further exploration of the role of this antibody is needed in patients with AAV.

Antineutrophil cytoplasmic antibody positivity and clinical implications in COVID-19.

Aim: To investigate clinical implications of antineutrophil cytoplasmic antibody (ANCA) positivity detected in COVID-19 patients during follow up. Materials and methods: A retrospective survey in a hospital database was carried out to detect COVID-19 patients in which ANCAs had been tested. Clinical, laboratory and imaging data were collected from this hospital database and compared between ANCA-negative and -positive patients. Results: ANCAs were tested in 87 COVID-19 patients. Eight had positivity in at least one ANCA test. COVID-19 symptoms on admission and rate of pulmonary involvement were similar. Acute phase reactant levels were higher in ANCA-positive patients. Rate of mortality was higher in the ANCA-positive group without statistical significance. Conclusion: ANCA positivity detected during COVID-19 in patients without a prior diagnosis of any rheumatic condition may be related with worse outcomes.

Association of antineutrophil cytoplasmic antibody (ANCA) specificity with demographic and clinical characteristics of patients with ANCA‑associated vasculitides.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by the presence of proteinase‑3 (PR3) or myeloperoxidase (MPO) ANCA. In over 90% of cases, PR3‑ANCA is associated with granulomatosis with polyangiitis (GPA). However, it is also rarely found in microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). On the other hand, MPO‑ANCA being characteristic of MPA (>90% of cases), is also found in about 40% of EGPA and 5% of GPA patients. On the ground of this overlap, clinical importance of ANCA specificity identification has been questioned. In this study, we analyzed the clinical and demographic characteristics of AAV subgroups identified by ANCA serotype. We conducted a multicenter study of AAV patients (417 GPA, 106 MPA, 102 EGPA; diagnosed between 1990 and 2016), included in the POLVAS registry. The data were systematically collected according to a standardized protocol. In the ANCA-positive group (anti‑MPO, anti‑PR3) a male-to-female ratio was 1:1, whereas in the ANCA-negative group it was 1:2, regardless of AAV diagnosis. Anti‑MPO antibodies were present in significantly older patients. Patients with MPO+GPA and MPO+EGPA were older than those with corresponding ANCA‑negative GPA and EGPA as well as PR3+AAV. Moreover, ANCA‑negative AAV was characterized by a low risk of end‑stage kidney disease and death. The presence and specificity of ANCA in AAV patients are related to sex and age, determine their organ involvement and influence mortality as previously shown. Patients with MPO‑ANCA-positive AAV constitute a clinically homogeneous group, whereas PR3‑ANCA-positive patients are much more clinically heterogeneous. ANCA-negative AAV patients are characterized by better prognosis. Thus, ANCA identification is an indispensable element and should not be omitted in establishing AAV diagnosis.

Elevated Myeloperoxidase-DNA Complex Levels in Sera of Patients with IgA Vasculitis

Introduction: IgA vasculitis is a systemic disease that results from the entrapment of circulating IgA-containing immune complexes in small-vessel walls in the skin, kidneys, and gastrointestinal tract. An excessive formation of neutrophil extracellular traps (NETs) is involved in the pathogenesis of vasculitis, especially in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This study aimed to clarify whether NETs are implicated in IgA vasculitis. Methods: Twenty-two patients with IgA vasculitis and 4 healthy volunteers were enrolled in this study. Serum levels of myeloperoxidase (MPO)-DNA complex, a fragment derived from NETs, were determined by enzyme-linked immunosorbent assay (ELISA), and the association between MPO-DNA complex levels and clinical parameters was examined. The presence of the ANCA was also assessed by ELISA specific for MPO and proteinase 3 (PR3) and indirect immunofluorescence (IIF), followed by assessing the differences in clinical parameters with and without the ANCA. Results: Serum MPO-DNA complex levels were significantly higher in patients with IgA vasculitis than those in healthy controls. A significant positive correlation between the serum MPO-DNA complex and IgA levels was noted. Interestingly, 63.6% of IgA vasculitis patients were ANCA-positive in IIF with an atypical pattern, whereas neither MPO-ANCA nor PR3-ANCA was detected by ELISA. These findings indicated that some IgA vasculitis patients possessed the so called minor ANCA. Serum IgA and MPO-DNA complex levels and the frequency of hematuria in the minor ANCA-positive group were significantly higher than in the minor ANCA-negative group. Conclusion: The collective findings suggested that NETs are certainly involved in the pathogenesis of IgA vasculitis.

Clinicopathological features of children with lupus nephritis with positive antineutrophil cytoplasmic antibody

Objective To study the clinicopathological features of children with lupus nephritis (LN) with positive anti-neutrophil cytoplasmic antibody (ANCA). Methods A retrospective analysis was performed for the children who were diagnosed with LN in the First Affiliated Hospital of Sun Yat-sen University from January 2003 to December 2019. According to the results of serum ANCA, they were divided into two groups: ANCA-positive group (n=59) and ANCAnegative group (n=454). The two groups were compared in terms of clinical manifestations, histopathological features, remission rate, and prognosis. Results Compared with the ANCA-negative group, the ANCA-positive group had a significant reduction in leukocytes and a significant increase in erythrocyte sedimentation rate (P 0.05). A total of 308 children underwent kidney biopsy. The results on light microscopy showed that compared with the ANCAnegative group, the ANCA-positive group had a significantly higher proportion of children with cellular fibrous crescents (P 0.05). Conclusions Children with ANCA-positive LN tend to have more severe renal pathological injury, which is not exactly parallel with clinical manifestations, suggesting that timely renal biopsy is of great importance.

Association between the antineutrophil cytoplasmic antibody and late coronary arterial occlusive disease in patients with Takayasu arteritis

BackgroundNo study has provided evidence of the clinical significance of the antineutrophil cytoplasmic antibody (ANCA) in patients with Takayasu arteritis (TAK). Therefore, we investigated the frequency of ANCA positivity and its clinical implications in patients with TAK. MethodsWe retrospectively reviewed the medical records of 121 patients with established TAK, who had results for ANCA status at diagnosis. We collected demographic and clinical data and the ANCA results at diagnosis. Additionally, we obtained information on patients’ medications and complications during follow-up. Early coronary arterial occlusive disease (CAOD) and late CAOD were defined based on a 30-day interval after TAK classification. The chi-square test, Fisher's exact test, Mann–Whitney test, and Kaplan–Meier survival analysis were used to analyze the data. ResultsThe patients’ mean age was 44.6 years, and 21 patients were men (17.4%). ANCA was detected in 8 patients (6.6%), of which 2 had both the myeloperoxidase ANCA (or perinuclear ANCA) and proteinase 3 ANCA (or cytoplasmic ANCA). Early CAOD was observed in 10 patients (8.3%), and late CAOD was found in 9 patients (7.4%). In the comparative analysis, the proportion of late CAOD exhibited a tendency to increase in the ANCA-positive group compared to that in the ANCA-negative group. Kaplan–Meier analysis showed that patients with ANCA exhibited a lower cumulative late CAOD-free survival rate than those without ANCA (p=0.012). When the algorithm for the classification of ANCA-associated vasculitis (AAV) proposed by the European Medicine Agency in 2007 was applied to 8 patients with ANCA, all were not reclassified as having AAV. ConclusionsANCA can be detected in a minority of patients with established TAK, and it may not contribute to the reclassification of AAV. Furthermore, ANCA positivity may be associated with late CAOD in patients with TAK.

Clinicopathologic characteristics and outcomes of lupus nephritis with positive antineutrophil cytoplasmic antibody

Aims The aim was to determine whether anti-neutrophil cytoplasmic antibody (ANCA)-positive serology in patients with lupus nephritis (LN) is associated with different clinicopathologic features and outcomes. Methods In our retrospective analysis, 283 patients were enrolled between 2013 and 2018. Thirty-six patients were ANCA-positive, and this group was compared with the remaining 247 patients who were confirmed as ANCA-negative at the time of biopsy. Results ANCA-positive LN patients exhibited higher anti-dsDNA antibody titers and serum creatinine levels and lower serum hemoglobin concentrations than ANCA-negative LN patients. On pathological evaluation, segmental endocapillary hypercellularity observed by light microscopy was significantly more common in the ANCA-positive group. This feature was not significantly different in the treatment group, but the response to treatment was significantly different, as was remission (76.1% vs 69.4%, p < 0.001), between the ANCA-negative and ANCA-positive groups. During follow-up, the times to renal replacement therapy (RRT) and death were significantly different between the two unmatched groups (chi-square test, p = 0.041). Multivariate Cox analysis revealed that neurological disorders, ANCA positivity, and the chronicity index (CI) remained independent risk factors for patient survival. Pulmonary infection was the main cause of death and was most often due to fungal infection. Conclusion ANCA-positive LN patients typically exhibited higher anti-dsDNA antibody titers, lower serum hemoglobin concentrations and worse renal function than ANCA-negative LN patients. Fungal infection was the main cause of death. We observed that ANCA positivity was an independent risk factor for patient survival.

Positive antineutrophil cytoplasmic antibody serology in patients with lupus nephritis is associated with distinct histopathologic features on renal biopsy

Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. ANCAs are present in a significant proportion of patients with lupus nephritis. Here we determine whether ANCAs are associated with distinct clinical and histopathologic features of lupus nephritis. Thirty-two ANCA-positive biopsies were compared to 222 ANCA-negative biopsies from patients with lupus nephritis. The majority (82%) of ANCA-positive patients had antimyeloperoxidase antibodies. Class IV-S lupus nephritis and glomerular necrosis were significantly more common (36% vs. 16% and 35% vs. 15%, respectively) and isolated Class V lupus nephritis significantly less common (10% vs. 29%) in the ANCA-positive group. ANCA-positive patients had significantly higher dsDNA titers (335u/ml vs. 52u/ml), significantly lower serum C4 concentrations (0.125g/L vs. 0.15g/L) and significantly higher serum creatinine (130μmol/L vs. 84μmol/L) at the time of biopsy. Hence ANCAs appear to influence the histological pattern of lupus nephritis and are associated with worse baseline renal function and more active lupus serology. There was no significant difference in outcome between groups when matched for severity of disease and treatment using propensity scoring. Thus, further studies are needed to examine whether ANCAs in patients with lupus nephritis have a pathogenic role and whether they are associated with worse renal outcomes or are simply a marker of more severe disease.

Clinicopathologic Characteristics and Outcomes of Lupus Nephritis With Antineutrophil Cytoplasmic Antibody: A Retrospective Study.

Few studies have analyzed the clinicopathologic characteristics and outcomes of lupus nephritis (LN) patients with antineutrophil cytoplasmic antibody (ANCA).The clinical and renal histopathologic data of 154 patients with biopsy-proven LN from 2011 to 2013 were analyzed retrospectively. The patients were followed up for a median period of 16.8 ± 9.4 months, and their outcomes were analyzed. Multivariate Cox analysis was used to evaluate the independent factors for poor outcomes.Among the 154 LN patients, 26 (16.88%) were seropositive for ANCA. The incidences of alopecia, oral ulcer, photosensitivity and skin lesion, and psychosomatic manifestations in the ANCA-positive group were significantly higher than in the ANCA-negative group (P = 0.007, 0.02, 0.02, and 0.03, respectively). Compared with the ANCA-negative group, the ANCA-positive group had significantly lower levels of complement C3 (P = 0.03). Additionally, the positive rate of antinucleosome antibodies, antihistone antibodies, antimitochondrial antibody M2, and anticardiolipin antibodies were higher significantly in the ANCA-positive patients than in the ANCA-negative patients (P = 0.001, 0.001, 0.03, 0.005, respectively). The ANCA-positive group had a notably higher chronic index than the ANCA-negative group (P = 0.01). During the follow-up, the complete remission rate in the ANCA-negative group was higher than that in the ANCA-positive group (P = 0.01). The cumulative renal survival rate in the ANCA-positive group was significantly lower than in the ANCA-negative group (log-rank = 6.59, P = 0.01). Multivariate Cox analysis revealed that the reduced estimated glomerular filtration rate (HR, 1.02; 95% confidence interval, 1.01 to 1.03; P = 0.005), NLR (HR, 1.20; 95% confidence interval, 1.02 to 1.40; P = 0.03), and ANCA (HR, 3.37; 95% confidence interval, 1.12 to 10.09; P = 0.03) were independent risk factors for patients’ renal survival after adjusting for age, sex, crescent formation, and glomerulosclerosis.The study found ANCA in LN patients is not rare, and patients with ANCA present with more severe clinicopathologic injuries. Thus, ANCA is an independent risk factor for poor renal outcomes in LN patients.

A historical study of American patients with anti-neutrophil cytoplasmic antibody negative pauci-immune glomerulonephritis.

Anti-neutrophil cytoplasmic antibodies (ANCA) play an important role in the pathogenesis of ANCA-associated vasculitis. The lack of ANCA antibodies may indicate a variation in clinical presentation and outcomes of this disease. We identified 74 adult patients between 1995 and 2009 with the diagnosis of pauci-immune glomerulonephritis. Demographics, histological features, and treatment outcomes were compared between ANCA-positive and ANCA-negative patients. These factors were correlated with renal function at presentation and follow-up. Of the 74 patients, 57 were ANCA-positive, and 17 were ANCA-negative. Demographics and mean Birmingham Vasculitis Activity Score were similar between ANCA-negative and ANCA-positive patients at presentation. Renal function was significantly worse at presentation in the ANCA-negative patients (eGFR 16.59 vs. 31.89ml/min/1.73m(2), p = 0.03). Patients in the ANCA-negative group had a significantly higher interstitial fibrosis score compared to the ANCA-positive group (2.1 vs.1.6, p = 0.04). The median time to remission was shorter in the ANCA-negative patients (51 vs. 78days, p = 0.01). Long-term renal function and 1-year patient and renal survival were similar between ANCA-negative and ANCA-positive patients. Baseline eGFR, percentage of normal glomeruli, glomerular sclerosis, and tubulointerstitial scarring predicted eGFR at 1year in both groups similarly. This is the first historical review of American patients with pauci-immune glomerulonephritis, comparing patients with ANCA-negative and ANCA-positive serology. Although ANCA-negative patients present with lower eGFR and more interstitial fibrosis, 1-year and long-term outcomes in both groups are similar.

Renal Neutrophils Infiltration in Antineutrophil Cytoplasmic Antibodies-Negative Pauci-Immune Crescentic Glomerulonephritis

IntroductionThis study aims to investigate the evidence of neutrophil infiltration in renal tissue from patients with antineutrophil cytoplasmic antibodies (ANCA)-negative pauci-immune crescentic glomerulonephritis (CrGN), and a comparison with their ANCA-positive counterparts was performed. MethodsRenal biopsy specimens from 31 patients with pauci-immune CrGN were collected. Twelve patients were ANCA negative, and 19 patients were ANCA positive. Neutrophil infiltration was investigated by staining of 2markers, CD15 and myeloperoxidase (MPO), using immunohistochemistry. ResultsPositive-stained cells of CD15 (CD15+) and MPO (MPO+) were mainly located in glomeruli with cellular crescents and segmental fibrinoid necrotic lesions and in periglomerular area of cellular crescents, especially at the area of ruptured Bowman capsule. Scanty positive staining was found in normal renal tissue. The number of CD15+ cells in the glomeruli and periglomerular area was significantly higher in ANCA-negative group than in ANCA-positive group (in glomeruli: 2.70 ± 1.61 versus 1.38 ± 0.85, P=0.019; in periglomerular area: 4.35 ± 4.36 versus 1.48 ± 1.67, P=0.047). The number of MPO+cells in the periglomerular area was also significantly higher in ANCA-negative group than that in ANCA-positive group. ConclusionsRenal neutrophil infiltration might play a pathogenic role in ANCA-negative pauci-immune CrGN, and the neutrophil infiltration might be more severe in ANCA-negative pauci-immune-CrGN than in ANCA-positive one.

Clinicopathologic analysis of 34 patients with microscopic polyangitis

To study the clinicopathologic features of microscopic polyangitis (MPA), and to compare the differences in anti-neutrophil cytoplasmic autoantibody (ANCA)-positive and ANCA-negative patients, as well as in ANCA-positive cases with or without glomerular immunoglobulin deposition. Thirty-four biopsy-proven cases of MPA were retrieved from the archival files of the Department during the past 7 years. The clinicopathologic characteristics between ANCA-positive and negative patients, as well as between ANCA-positive cases with and without glomerular immunoglobulin deposition, were compared. Amongst the 34 MPA patients studied, about one-fifth to one-half were accompanied by various extrarenal symptoms. Serum ANCA was positive in 26 patients (76.5%). A slight to moderate increase in urinary protein was demonstrated in 31 patients, while 3 patients had nephrotic syndrome. Elevated serum creatinine was detected in 32 cases. Renal biopsy revealed crescentic glomerulonephritis in 24 cases, focal segmental glomerulonephritis in 8 cases, vascular fibrinoid necrosis with inflammation in 7 cases, intimal thickening of arterioles in 24 cases, interstitial inflammatory cells, including neutrophil infiltration (21 cases), in 29 cases. Crescentic formation was more common in the ANCA-positive group than in the ANCA-negative group (P < 0.05). Amongst the 26 ANCA-positive cases, 10 had glomerular immunoglobulin deposits (including 1 case with IgA nephropathy). In general, these cases had a greater degree of proteinuria than those without glomerular immunoglobulin deposits (P < 0.05). The diagnosis of MPA relies on histologic examination of renal biopsy and clinicopathologic correlation. Serum ANCA seems important for glomerular crescent formation. Glomerular immunoglobulin deposition may also play a significant role in the exacerbation of proteinuria.

Antineutrophil cytoplasmatic antibodies in patients with premature atherosclerosis: prevalence and association with risk factors

Autoimmunity is suggested to play a role in premature atherosclerosis. Antineutrophil cytoplasmatic antibodies (ANCA) are a group of autoantibodies found in several inflammatory disorders in which they supposedly amplify the inflammatory process. In this study the hypothesis is tested that ANCA play a role in premature atherosclerosis. Cross-sectional study followed by nested case-control study. In a total of 286 consecutive patients with premature atherosclerosis (age < 55 years) ANCA were tested. Within the same cohort, a nested case-control study in 16 ANCA-positive patients and 32 ANCA-negative controls matched for sex, and site of atherosclerosis, was executed. University hospital outpatient clinic for lipids and premature atherosclerosis. A total of 286 consecutive patients with premature atherosclerosis (age < 55 years). Prevalence of ANCA was 5.6% (16 of 286). All cases had perinuclear ANCA (pANCA); no cytoplasmatic ANCA was found. Mean age was 42 +/- 7 in the ANCA-positive vs. 42 +/- 9 years in the ANCA-negative group (P=ns). More female parents were ANCA-positive (8M/8F vs. 200M/70F, P=0.03). Patients with ANCA had more often peripheral vascular disease (37.5 vs. 15.2%, P=0.03). In the case-control study levels of Lp(a) were higher (43.8 vs. 15.6% >300 mg x L(-1), P=0.05), whereas levels of HDL-c were lower in ANCA-positive patients (0.84 +/- 0.26 vs. 1.06 +/- 0.27 mmol x L(-1), P=0.01). Markers of inflammation, C-reactive protein (CRP) and serum amyloid A (SAA), did not differ, nor did antibodies against oxidized-LDL and malondialdehyde (MDA)-LDL, markers for the extent of atherosclerosis. Our results suggest that ANCA do not appear to play a major role in premature atherosclerosis as there was no increased prevalence of the autoantibody. Moreover, no differences in the incidence of classical cardiovascular risk factors nor in serum levels of markers of inflammation were found between the ANCA-positive group as compared with the ANCA-negative group.