ANCA-negative 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.

#2291 ANCA negative vasculitis—the unmet need within small vessel vasculitis

Abstract Background and Aims ANCA negative small vessel vasculitis with renal involvement has been described in a number of cohorts. Though comprehensive studies comparing these individuals to ANCA positive patients are lacking and they are routinely excluded from clinical trials. Whilst the numbers are smaller than those with ANCA positivity, they still make up a large proportion of small vessel vasculitidies (Fig. 1). The absence of detectable circulating ANCA is thought to indicate a distinct spectrum of the disease. There remains unanswered questions regarding the pathophysiology, diagnosis and management of patients with seronegative AAGN. We present data from Croatian referral center. Method Study included 106 AAV patients with biopsy proven renal involvement in the period from 2007-2017. Category variables were analysed with Fisher Exact test and continuous with Kruskal-Wallis test. Statistical difference was then analysed post hoc with Chi-square test. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between clinical phenotypes and finding significant predictors regarding outcomes which were defined as combined outcome end-stage renal disease and death (ESRDD), ESRD alone, the death outcome alone and relapse rate. Results 106 AAV patients with renal involvement were included: 66 (61.1%) MPA, 20 (18.5%) GPA, 20 (18.5%) RLV. 14 (13%) were PR3-ANCA positive, 57 (52.8%) MPO ANCA positive, 5 (4.6%) PR3-ANCA+MPO-ANCA and 32 (29.6%) ANCA negative patients. ANCA negative patients were comparatively younger (p = 0.02) and presented with more renal limited vasculitis (RLV; p &amp;lt; 0.001), lower BVAS (p = 0.003) and lower CRP (p = 0.001). ANCA negative patients usually presented with nephrotic syndrome compared to positive ones which presented with rapid progressive nephritic syndrome or acute nephritic syndrome (p = 0.027). 24-hour proteinuria levels were higher in ANCA negative group (p = 0.003). Though statistical difference was not reached, there was tendency for ANCA negatives to receive less plasmapheresis (p = 0.074). Histologically there were no differences between ANCA positive and ANCA-negative patients. On sub analysis ANCA negatives versus individual seropositive groups, there was tendency that ANCA negatives and MPO-ANCA patients had lower percentage of glomerular crescents (p = 0.092) but more acute tubular damage (p = 0.087). There were no differences in clinical outcomes between the groups. Conclusion ANCA negative vasculitis form a large proportion of small vessel vasculitidies and present with different clinical laboratory and histological (renal) characteristics than ANCA positive ones. More often than not disease seems to be renal limited and patients tend to be younger. Due to the rarity of the disease, there remains unanswered questions regarding the pathophysiology, diagnosis and management of these patients. This study highlights noteworthy distinctions between the two groups. Whether these differences warrant adjustments in treatment algorithms or a reconsideration of the classification of small vessel vasculitis remains to be determined. Further investigation into the pathogenetic mechanisms of seronegative AAVs is essential.

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.

MO290CLINICAL DIFFERENCES AND OUTCOMES IN ANCA ASSOCIATED VASCULITIS PATIENTS ACCORDING TO SEROLOGICAL PHENOTYPE – EXPERIENCE FROM CROATIAN REFERRAL CENTER

Abstract Background and Aims ANCA associated vasculitis (AAV) are usually classified according to clinical presentation (Chapel-Hill consensus conference). There is however suggestion by some authors that AAVs could be classified according to ANCA specificity. We aimed to compare AAV patients in our cohort according to serological phenotype. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. Category variables were analysed with Fisher Exact testom and continuous with Kruskal-Wallis testom. Statistical difference was then analysed posthoc with Chi-square test. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to &amp;lt;15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Results The study included 106 AAV patients with renal involvement: 66 (61,1%) MPA, 20 (18,5%) GPA, 20 (18,5%) RLV. There were 14 (13%) PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA and 32 (29,6%) ANCA negative patients. Average SCr was 316,5 μmol/l (IQR 207,0-548,5), 24-hour proteinuria median was 1,7g/24h (IQR 0,8-2,8). Clinicaly PR3 positive AAVs had significantly more ENT (p&amp;lt;0,001) and skin (p=0,001) involvement, and ANCA negatives had significantly less lung involvement (p&amp;lt;0,001), and less expressed constitutional symptom (p=0,031). Interestingly both MPO and PR3 positive AAV patients had approximately equal percentage of lung involvement. Both PR3 (p=0,021) and MPO (p=0,009) positive AAVs had higher BVAS score compared to ANCA negatives, while on average there was no significant difference between MPO, PR3 and double positives. PR3 (p=0,007) and MPO (p=0,003) positive AAVs had higher CRP levels than ANCA negatives, and PR3 AAVs had on average higher CRP than MPO AAVs though not statistically significant. There was strong tendency (p=0,087) to PR3 AAVs having more acute tubular damage than other groups and also strong tendency (p=0,092) of having more crescentic formations than MPO AAVs and ANCA negatives but similar to double positives. Though it was not statistically significant ANCA negatives had higher median of IFTA compared to other groups. PR3 AAVs and double positives required significantly more often treatment with PLEX (p=0,042) and dialysis (p=0,04) compared to MPO positive AAVs and ANCA negatives. We then grouped patients into ANCA positives and ANCA negatives. ANCA negative patients were younger (p=0,02), expressed clinicaly more as RLV (p&amp;lt;0,001). BVAS score was lower in ANCA negative group (p= 0,003). ANCA positive patients presented more often with RPGN (p=0,027) and ANCA negatives with nephrotic syndrome. There was tendency of ANCA positives being treated with PLEX more often (p=0,074). In the primary outcome analysis there were no statistically significant differences between serological phenotypes though for relapse rate (p=0,155) curve dynamics through follow up time seems to show higher relapse rate for PR3 and double positive AAVs after 2 years of follow up. Conclusion Serological classification of AAVs is an interesting way for overcoming the limitations of clinical classification. Apart from differences between MPO, PR3 and double positive AAVs, it appears there are even more significant differences between ANCA positive and negative ones.

What is the meaning of ANCA positivity in IgG4-related disease?

To evaluate the prevalence and meaning of antineutrophil cytoplasmic antibodies (ANCA) positivity in a cohort of IgG4-related disease (IgG4-RD). We identified patients with ANCA determination from a retrospective cohort of 69 patients with IgG4-RD. ANCA were measured by indirect immunofluorescence microscopy (IIF) and/or proteinase 3 (PR3)-ANCA and MPO-ANCA by ELISA. IIF patterns were classified as perinuclear (P-ANCA), cytoplasmic (C-ANCA) and atypical (X-ANCA). We compared the ANCA-positive vs the ANCA-negative IgG4-RD group. Out of 69 patients, 31 IgG4-RD patients had an ANCA determination. Four patients with concomitant systemic autoimmune diseases were excluded. We found positive ANCA by IIF in 14 (56%) of 25 patients tested. The most common IIF pattern was C-ANCA in eight (57.1%), followed by dual C-ANCA/X-ANCA in four (28.6%) and P-ANCA and dual C-ANCA/P-ANCA in one each (7.1%). Of the 20 patients with ANCA determination by both IIF and ELISA, four have positive ANCA by ELISA (three for MPO-ANCA and one for PR3-ANCA). Of the two patients with only ELISA determination, one was positive for MPO-ANCA. The prevalence of ANCA positivity by ELISA was 22.7% (5 out of 22 patients). ANCA was more frequent in the Mikulizc/systemic phenotype (42.9%) compared with other phenotypes (P=0.04). ANCA-positive IgG4-RD patients had more frequently lymph node and kidney involvement, high IgG1 levels and erythrocyte sedimentation rate, and positive antinuclear antibodies. ANCA are found in a significant number of patients with IgG4-RD and differed from the ANCA-negative group in terms of clinical and serological features.

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.

P0383A LONG-TERM RETROSPECTIVE OUTCOME ANALYSIS OF ANCA-NEGATIVE PAUCI-IMMUNE GLOMERULONEPHRITIS

Abstract Background and Aims Pauci-immune glomerulonephritis (GN), usually associated with circulating antineutrophil cytoplasm antibodies (ANCA), is one of the most common causes of rapidly progressive glomerulonephritis that results in high incidence of end-stage kidney disease (ESKD). Most of the existing large trials looking at treatment efficacies exclude ANCA-negative patients, and relatively few studies have reported their long-term outcomes. Therefore, we conducted a single-centre retrospective study to examine the long-term overall survival and renal outcome in this cohort of patients. Method All cases of newly diagnosed biopsy-proven pauci-immune GN from 2006 - 2019 were identified through a local histopathology database. Patients with negative anti-myeloperoxidase (MPO) and anti-proteinase-3 (PR3) serology were identified (ANCA-negative group) and comparisons made with the cohort of patients with positive serology (MPO/PR3 positive group). Patients with relapsing ANCA-GN, eosinophilic granulomatosis with polyangitis, other co-existing glomerulonephritis or missing data on induction therapy or outcome were excluded. Baseline demographics, initial serum creatinine (sCr), estimated glomerular filtration rate (eGFR), systemic involvement and histopathology features including percentage normal glomeruli, and interstitial fibrosis/tubular atrophy score of &amp;gt;25% were collected and compared. Kaplan Meier survival analysis was used to compare overall survival and end-stage kidney disease (ESKD) progression rate between the two groups. Results 178 patients were identified with a median follow-up of 44 months. 83 were female (47%) and median age was 62 years. 15 (8%) were ANCA-negative. 163 (92%) were MPO- and/or PR3-ANCA positive. There were no differences in baseline characteristics such as age, gender and proportion of patients with normal glomeruli &amp;lt;25% on initial histology. However, we observed a significantly higher proportion of patients with renal-limited vasculitis in the ANCA-negative group (67% vs 24% p=0.01) and more severe renal dysfunction at presentation (median sCr 309umol/L vs 204umol/L, p= 0.01). We also demonstrated a higher proportion of patients with an IFTA score of &amp;gt;25% on renal biopsy (53% with &amp;gt;25% IFTA in ANCA-negative cohort vs 27%, p =0.03). The ANCA-negative group were more likely to receive combination immunosuppressive therapy that included plasma exchange (47% vs 23%, p value 0.04). When considering overall survival there was significantly higher mortality (40% vs 16%, p value 0.009) and rate of progression to ESKD (53% vs 18%, p value 0.001) in the ANCA-negative group as a whole. When we compared patients with renal-limited vasculitis only however, there was no significant difference in either overall survival or rate of progression to ESKD (p=0.85 and 0.84 respectively). We found that ANCA-negative patients with systemic disease did still have significantly higher rates of both progression to ESKD and overall mortality (p=0.002 and p=0.02 respectively). Conclusion In our cohort, patients with ANCA-negative pauci-immune GN have poorer renal function and higher IFTA scores on biopsy at presentation perhaps reflecting delayed diagnosis due to a lack of diagnostic serology and the higher proportion of renal-limited disease in this subgroup. Despite intensive immunosuppressive therapy, this study observed overall higher treatment failure rates in ANCA-negative patients, largely in those with systemic disease. This possibly relates to a different underlying disease process. Larger, prospective studies are required to enhance understanding of the disease pathogenesis to allow optimal tailored treatment for these patients.

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.

Clinical characteristics of infective endocarditis in patients with antineutrophil cytoplasmic antibody or antiphospholipid antibody: a retrospective study in Shanghai

ObjectiveThis study aimed to characterise rheumatic manifestations and autoantibodies in 432 patients diagnosed with infective endocarditis (IE) in Shanghai.Design, setting and participantsA retrospective study was conducted in Ruijin Hospital from...

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.