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Purpose: To investigate the diversity of ocular manifestations in patients with positive perinuclear antineutrophil cytoplasmic antibody (p-ANCA). Methods: The clinical records of five patients exhibiting ocular manifestations and testing positive for serum MPO-ANCA were retrospectively reviewed. Results: Three out of five patients were female. The youngest patient was aged 26, whereas the eldest was 83 years old. 80% (n = 4) of them had purely anterior segment involvement, with the commonest manifestation being peripheral ulcerative keratitis and scleritis. Only one patient had posterior segment involvement, specifically posterior ischemic optic neuropathy. Two patients demonstrated unilateral involvement. There was only one patient diagnosed with systemic involvement, presenting as mixed nephrotic and nephritic syndrome, who required a course of intravenous methylprednisolone during the active stage. Three patients required second-line immunosuppressants throughout the course due to frequent relapse. Conclusion: Anterior segment ocular manifestations are not uncommon and can be the initial presentation of p-ANCA-associated vasculitis (AAV). Therefore, its evaluation should be considered in establishing the diagnosis of AAV, a life-threatening disease. [ABSTRACT FROM AUTHOR]

Introduction/objectives: Patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) experience reduced health-related quality of life (HRQoL). Global assessment tools use visual analogue scales to provide patients' and physicians' views on disease activity or the patient's overall health and well-being. The aim of this study was to examine the relationships between patient and physician global assessments (PtGA and PhGa) as they relate to overall health in people with AAV. Methods: Patients with AAV attending a tertiary vasculitis clinic participated in this prospective observational study. The primary outcome measured was PtGA and PhGA scores, with higher scores representing better health. SF-36 assessed HRQoL. Discordant scores were defined as an absolute difference of ≥ 20 between PhGA and PtGA. Results: Ninety-seven patients (mean age 58 years, 46% male) participated. Most were taking immunosuppressive therapy (88%) and had kidney involvement (79%). The mean PhGa and PtGA were similar (mean difference − 2.6, [CI] 0.5, 4.7). Physicians' global assessments were lower in the 43 (44%) patients with active disease, with a trend towards a lower PtGA in this group. Patients' global assessments were ≥ 20 points higher than PhGAs in 16 patients and ≥ 20 points lower in 10 patients. Negatively discordant patients (PtGA < PhGA) were older and less likely to have active disease than positively discordant patients. Conclusions: Physicians did not systematically overestimate patients' global health when using the global assessment tool. Discordance rates were 26%, within which, physicians were more likely to assess the patient's health lower than patients themselves. Key Points • There remains an unmet need for patient-reported outcomes assessing quality of life in AAV and other diseases. • The global assessment tool correlates with SF-36 which is commonly used as a tool for assessing quality of life. • Physicians do not tend to overestimate patient's global health both overall and within the discordant sub-group. • Assessing PtGA/PhGA discordance could identify unmet priorities for patients and improve shared physician–patient decision-making. [ABSTRACT FROM AUTHOR]

CAR-T cell therapy, a cutting-edge cellular immunotherapy with demonstrated efficacy in treating hematologic malignancies, also exhibits significant promise for addressing autoimmune diseases. This innovative therapeutic approach holds promise for achieving long-term remission in autoimmune diseases, potentially offering significant benefits to affected patients. Current targets under investigation for the treatment of these conditions include CD19, CD20, and BCMA, among others. However, CAR-T therapy faces difficulties such as time-consuming cell manufacturing, complex and expensive process, and the possibility of severe adverse reactions complicating the treatment, etc. This article examines CAR-T therapy across various rheumatic autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic sclerosis (SSc), antisynthetase syndrome (ASS), and ANCA-associated vasculitis (AAV), highlighting both therapeutic advancements and ongoing challenges. [ABSTRACT FROM AUTHOR]

Objective: Describe the proportion of patients with wide-field fluorescein angiographic (WFFA) findings in patients with active anterior scleritis. Methods: An observational, descriptive, cross-sectional study of the WFFA findings of patients with active anterior scleritis including nodular, diffuse, or necrotizing involvement was performed. Studies were performed with the Heidelberg Spectralis module (102º). Images were saved and assessed by two masked co-authors. Results: Seventy-nine eyes from 39 patients, 31 (79%) females with a mean age of 50.5 years ± 13.98. Mean best-corrected visual acuity (BCVA) of 0.1343 ± 0.2475 logMar or 20/27. WFFA findings were observed in 39.58% of eyes with active scleritis and in 16.66% of eyes without scleritis. Systemic association was present at 50%, with ANCA-associated vasculitis being the most prevalent. WFFA findings were more frequent in cases of anterior diffuse scleritis and correlated with scleritis severity when central and peripheral leakage (p < 0.022) and cystoid macular edema (p < 0.013) were present. Conclusions: Almost 40% of eyes with anterior scleritis have WFFA findings of vascular leakage and 16% of eyes without scleritis. Retinal vascular leakage needs to be explored as a sign of local and/or systemic activity in patients with anterior scleritis and may have implications for disease severity and management. [ABSTRACT FROM AUTHOR]

Although rapidly progressive glomerulonephritis (RPGN) is the main renal phenotype of microscopic polyangiitis (MPA), we aim to clarify the clinical features of slowly progressive MPA. This retrospective observational study included 12 patients diagnosed with MPA in our hospital between January 2012 and February 2022. We investigated the differences in surrogate markers, rate of decline of estimated glomerular filtration rate (eGFR) between the slowly progressive and rapidly progressive MPA groups. Of the 12 patients with MPA, 3 (25.0%) had slowly progressive MPA: MPA within 30% decrease in eGFR 3 months pretreatment, all of whom developed RPGN during the course. Patients with slowly progressive MPA had lower levels of C-reactive protein, myeloperoxidase anti-neutrophil cytoplasmic antibodies, and interleukin-6; higher levels of sialylated carbohydrate antigen KL-6. Slowly progressive MPA is not uncommon in our hospital. A linear relationship was found between slower rate of eGFR decline and lower surrogate markers of disease activity. Some MPA cases have slowly progressive glomerulonephritis leading to RPGN, which may be clinically characterized by low disease activity. It may be useful to measure myeloperoxidase anti-neutrophil cytoplasmic antibody in chronic kidney disease with concomitant urinary abnormalities to diagnose MPA with slowly progressive glomerulonephritis. KEY LEARNING POINTS: Rapidly progressive glomerulonephritis is the main renal phenotype of microscopic polyangiitis (MPA), and slowly progressive MPA is rarely observed. Slowly progressive MPA was not rare in our hospital and was characterized clinically by low disease activity and complicated by interstitial pneumonia. When encountering patients with undiagnosed chronic kidney disease complicated by interstitial pneumonia, measuring myeloperoxidase anti-nuetrophil cytoplasmic antibody regardless of the rate of renal function decline, potentially leads to the diagnosis of slowly progressive MPA. [ABSTRACT FROM AUTHOR]

Abstract Background and objective Accumulated evidence supports the tendency of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis(AAV) to coexist with atherosclerosis (AS). However, the common etiology of these two diseases remains unclear. This study aims to explore the mechanisms underlying the concurrent occurrence of ANCA and AS. Methods Microarray data of AAV and AS were examined in a comprehensive gene expression database. Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis (GEO2R) were performed to identify common genes between AAV and AS. Based on the co-expressed genes, functional enrichment analysis, protein-protein interaction (PPI) network analysis, and identification of hub genes (HGs) were conducted. Subsequently, co-expression analysis of HGs was performed, and their expression and diagnostic value were validated. We further explored immune cell infiltration and analyzed the correlation between HGs and infiltrating immune cells. Finally, the reliability of the selected pathways was verified. Results The results of the common gene analysis suggest that immune and inflammatory responses may be common features in the pathophysiology of AAV and AS. Through the interaction of different analysis results, we confirmed five HGs (CYBB, FCER1G, TYROBP, IL10RA, CSF1R). The CytoHubba plugin and HG validation demonstrated the reliability of the selected five HGs. Co-expression network analysis revealed that these five HGs could influence monocyte migration. Analysis of immune cell infiltration showed that monocytes in ANCA and M0 macrophages in AS constituted a higher proportion of all infiltrating immune cells, with significant differences in infiltration. We also found significant positive correlations between CYBB, FCER1G, TYROBP, IL10RA, CSF1R, and monocytes/M0 macrophages in AAV, as well as between CYBB, FCER1G, TYROBP, IL10RA, CSF1R, and M0 macrophages in AS. Conclusion These five HGs can promote monocyte differentiation into macrophages, leading to the concurrent occurrence of AAV and AS. Our study provides insights into the mechanisms underlying the coexistence of AAV and AS.

Abstract Background Propylthiouracil is an antithyroid medication that is associated with ANCA positivity, often in the absence of clinically overt vasculitis. Propylthiouracil-induced ANCA-associated vasculitis (AAV) is characterized by multiple antigenicity and presents similarly to other forms of drug-induced vasculitis. Case presentation We report a case of a 49-year-old woman who developed propylthiouracil-induced AAV after 31 years of intermittent therapy. The patient presented with progressive respiratory and generalized symptoms. She was diagnosed with propylthiouracil-induced AAV with alveolar hemorrhage based on detection of ANCA and anti-MPO antibodies, exclusion of primary vasculitis, and symptom resolution following propylthiouracil withdrawal. The patient was treated with intravenous methylprednisolone, followed by oral prednisolone. Her symptoms resolved, and her laboratory and radiological tests improved within one week. Conclusions Research linking the duration of propylthiouracil use to the development of vasculitis is restricted by multiple methodological limitations. Maintaining a high index of clinical suspicion is a more reliable approach to detecting propylthiouracil-induced AAV than regular laboratory monitoring, given that patients with Graves’ disease may show ANCA positivity in the absence of medication use. Therefore, clinicians should remain vigilant for the varied presentations of propylthiouracil-induced AAV. Moreover, further research is recommended to investigate the possible link between the duration of PTU use and the onset of clinically overt vasculitis.

Although rapidly progressive glomerulonephritis (RPGN) is the main renal phenotype of microscopic polyangiitis (MPA), we aim to clarify the clinical features of slowly progressive MPA. This retrospective observational study included 12 patients diagnosed with MPA in our hospital between January 2012 and February 2022. We investigated the differences in surrogate markers, rate of decline of estimated glomerular filtration rate (eGFR) between the slowly progressive and rapidly progressive MPA groups. Of the 12 patients with MPA, 3 (25.0%) had slowly progressive MPA: MPA within 30% decrease in eGFR 3 months pretreatment, all of whom developed RPGN during the course. Patients with slowly progressive MPA had lower levels of C-reactive protein, myeloperoxidase anti-neutrophil cytoplasmic antibodies, and interleukin-6; higher levels of sialylated carbohydrate antigen KL-6. Slowly progressive MPA is not uncommon in our hospital. A linear relationship was found between slower rate of eGFR decline and lower surrogate markers of disease activity. Some MPA cases have slowly progressive glomerulonephritis leading to RPGN, which may be clinically characterized by low disease activity. It may be useful to measure myeloperoxidase anti-neutrophil cytoplasmic antibody in chronic kidney disease with concomitant urinary abnormalities to diagnose MPA with slowly progressive glomerulonephritis.

The anaphylatoxin C5a and its receptor C5aR (CD88) are complement pathway effectors implicated in renal diseases, including ANCA-associated vasculitis. We investigated the kidney expression of C5aR and a second C5a receptor C5L2 by using immunohistochemistry, in situ hybridization, and spatial gene expression on formalin-fixed, paraffin-embedded human and mouse kidney. C5aR was detected on interstitial macrophages and in multiple tubular regions, including distal and proximal; C5L2 had a similar expression pattern. The 5/6 nephrectomy model of chronic kidney injury exhibited increased C5aR expression by infiltrating cells within the fibrotic regions. C5aR expression was confirmed on human leukocytes and in vitro differentiated macrophages by flow cytometry, and treatment with C5a induced the expression of chemokines and remodeling factors by macrophages, including CCL-3/-4/-7, -20, MMP-1/-3/-8/-12, and F3, and promoted leukocyte survival. C5a activity was C5aR dependent, as demonstrated by reversal with the C5aR inhibitor avacopan. Collectively, these results suggest that myeloid C5aR may induce excessive inflammation in the kidney via immune cell recruitment, extracellular matrix destruction, and remodeling, resulting in fibrotic tissue deposition. [ABSTRACT FROM AUTHOR]

Copyright of Hypertonia és Nephrologia is the property of LifeTime Media Kft. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Cardiovascular diseases are the main causes of mortality in the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. Carotid intima-media thickness (CIMT) measurement and pulse wave velocity (PWV) were performed to determine atherosclerosis and arterial stiffness as cardiovascular risk markers. Patients and Methods: The data of 31 patients with AAV were compared with 21 healthy controls. Demographic and laboratory findings were recorded. Results: Seventeen patients (54.8%) were male. Mean age was 52.6±11.5 years. CIMT was higher in the patient group [0.74 (0.65 -- 0.84) vs 0.63 (0.57-0.74) mm; p=0.048]. PWV [7.9 (6.7-9.3) vs 7.8 (6.8-8.5) m/s; p=0.295] and augmentation index (AI) [22.5 (11.0-30.0) vs. 23 (9.5-30.5) mm/Hg, p=0.801] were similar in both groups. CIMT was correlated with age (r: 0.538, p<0.001) and PWV (r: 0.554 p< 0.001) while there was no correlation with AI (r: 0.047, p= 0.764). Conclusion: The present study showed that CIMT is significantly increased and correlated with age and PWV in patients with AAV compared to controls. CIMT can be used as a screening tool as part of patient follow-up to identify patients at cardiac risk. [ABSTRACT FROM AUTHOR]

Objective: Patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and systemic lupus erythematosus (SLE) are prone to infections. This study aims to clarify infectious complications in terms of both the disease and the specific treatments used. Patients and Methods: Sixty-three patients with SLE and AAV with kidney involvement treated with rituximab or cyclophosphamide were included. Patients were examined regarding infections, comorbidities, immunosuppressives, estimated glomerular filtration rate (eGFR), use of prophylactic antibiotics, hospitalization, and death. Results: Patients with SLE experienced more genitourinary infections in general (p=0.009). In the rituximab group, SLE patients had a higher incidence of genitourinary infections, septicemia, and intensive care unit admissions. Furthermore, lupus patients with serious infections were all treated with rituximab and had a higher incidence of low respiratory tract infections (p=0.003). On the contrary, treatment with rituximab did not cause an increased risk of infection among AAV patients compared to cyclophosphamide. In general, patients with serious infections had lower IgG and total Ig levels (p<0.05). Conclusion: Patients with SLE had a higher risk of genitourinary infections and also a higher risk of sepsis, serious infections, and hospitalizations when treated with rituximab. Immunoglobulin levels are associated with serious infections. [ABSTRACT FROM AUTHOR]

We report a case of Graves' disease in a patient who initially received carbimazole therapy, which was switched to propylthiouracil due to adverse effects. After 14 months of propylthiouracil therapy, the patient developed cutaneous ANCA-associated vasculitis. Prompt cessation of propylthiouracil and topical treatment led to complete resolution of the skin lesions. [ABSTRACT FROM AUTHOR]

We aimed to clarify the long-term safety and efficacy of rituximab (RTX) as a remission induction therapy following severe relapse in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV). We retrospectively collected the data of patients with severely relapsed AAV from a Japanese multicentre cohort. The primary exposure was RTX use; the primary outcome was complete remission (CR) proportions at week 24. Baseline characteristics were compared between the RTX and non-RTX groups. We performed multivariate logistic regression analysis and one-to-one propensity score matching analysis as a sensitivity analysis. Totally, 100 patients were enrolled: 52 in the RTX group and 48 in the non-RTX group. Baseline characteristics were comparable between the two groups, except for age, AAV subtype and ANCA serotype. The median age was 71 vs. 75 years, and the PR3-ANCA positivity rate was 44.2% vs. 18.8% in the RTX and non-RTX groups, respectively. No significant difference was observed in CR proportions at week 24 between the two groups (79.2% vs. 68.1%, p = 0.321), with an adjusted odds ratio of 1.27 (95% confidence interval [CI] 0.47–3.51). At week 48, CR proportions were significantly higher in the RTX group (91.7% vs. 64.9%, p = 0.005), with an adjusted odds ratio of 2.95 (95% CI 0.97–9.91). Serious infection rates were lower in the RTX group than in the non-RTX group, with no statistically significant difference. RTX was not superior to conventional immunosuppressive therapies at week 24 but showed significantly favourable results at week 48 for severely relapsed AAV. Key Points • RTX might be superior to traditional treatments as an induction therapy for severely relapsed AAV. • RTX has the potential to sustain long-term remission with fewer occurrences of infections in the treatment of severely relapsed AAV. [ABSTRACT FROM AUTHOR]

Objectives ANCA-associated vasculitis (AAV) is associated with significant morbidity, fatigue, pain and poor health-related quality of life (HRQoL). This review aims to assess the comprehensiveness of existing patient reported outcome measures (PROMs) used in AAV and identify associations with poorer HRQoL outcomes. Methods A literature review of studies using PROMs, including those labelled HRQoL in people with AAV as a primary or secondary study outcome were screened and reviewed up to July 2023. Quality was assessed using the Critical Appraisal Skills Programme. Results A total of 30 articles were included which utilised 22 different PROM tools, 76.7% (n  = 23) used the SF-36 or a variation as a generic measure of health status and or HRQoL. Two studies developed a disease-specific PROM. The AAV-PRO showed good psychometric properties but potential limitations in capturing all relevant aspects of the disease experience for AAV patients. Factors associated with poorer HRQoL included: neurological and sinonasal involvement, women and younger patients. A total of 86.6% of studies showed no meaningful relationships between the SF-36 and BVAS, VDI or disease duration. Depression and anxiety were common and socioeconomic factors such as unemployment were significantly associated with poorer mental health outcomes. Glucocorticoids were found to be independently associated with worse SF-36 scores. Conclusion Generic PROMs are useful in measuring significant changes but lack sensitivity to specific symptoms and unique AAV-related issues, while existing disease-specific PROMs have some limitations and may not fully capture the AAV patient's perspective on disease and treatment burden. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a severe autoimmune disease that often involves the upper and lower respiratory tracts. In recent years, numerous studies have found a significant increase in the incidence of cancer among AAV patients, but the association between lung cancer and AAV remains inconclusive, with relatively low clinical attention. This review summarizes the current literature on the risk of lung cancer in patients with ANCA-associated vasculitis (AAV), detailing the potential mechanisms by which AAV may contribute to lung cancer, and further elucidates the inherent carcinogenic risks of immunosuppressants.There is a correlation between AAV and lung cancer, which is related to T cell senescence and damage, as well as the abnormal expression of cytokines such as IL-6 and IL-10. In AAV patients, the use of cyclophosphamide and azathioprine (AZA) alone has a clear carcinogenic risk, with frequent use of CYC potentially posing a high risk for lung cancer. Although TNF inhibitors (TNFi) combined with CYC have carcinogenic risks, there is insufficient evidence to link them directly to an increased risk of lung cancer. For patients at high risk for lung cancer, the judicious use of immunosuppressants, timely computed tomography (CT), and lung cancer screening can reduce the risk of lung cancer in AAV patients. [ABSTRACT FROM AUTHOR]

Background The remission rate of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients who received standard induction therapy is far from satisfactory. Improving the remission rate of MPO-AAV patients is essential. Hydroxychloroquine (HCQ), one of the classic antimalarial drugs, has been widely used in various autoimmune rheumatic diseases. This retrospective observational cohort study is aimed to evaluate the efficacy and safety of HCQ during induction treatment for MPO-AAV. Methods The medical records of patients diagnosed with MPO-AAV at Xiangya Hospital, Central South University from January 2021 to September 2023 were collected. They were assigned to the HCQ group or control group according to whether they used HCQ. The patients included were screened by propensity score matching. To evaluate whether MPO-AAV patients benefited from HCQ, we compared the prognosis of the two groups. The adverse effects of HCQ during follow-up were recorded. Results The composition ratio of complete remission, response and treatment resistance between HCQ group and control group were different statistically (P = .021). There was no significant difference between the two groups in 1-year renal survival (P = .789). The HCQ group had better 1-year patient survival than the control group (P = .049). No serious adverse effects were documented in the HCQ group. Conclusions HCQ together with standard induction treatment may improve the remission rate of MPO-AAV patients, and HCQ had good safety in our study. [ABSTRACT FROM AUTHOR]

Background Kidney involvement is common in anti-neutrophil cytoplasm antibody–associated vasculitis (AAV) and the prognosis is determined by the severity of kidney damage. This study focused on long-term kidney outcomes, defining possible risk factors and comparing the performance of three different histological classifications to predict outcomes for patients with AAV. Methods The dataset included 848 patients with newly diagnosed AAV who participated in seven randomized controlled trials (RCTs) (1995–2012). Follow-up information was obtained from questionnaires sent to the principal investigators of the original RCTs. Results The cumulative incidence of end-stage kidney disease (ESKD) at 5 and 10 years was 17% and 22%, respectively. Patients who developed ESKD had reduced patient survival compared with those with preserved kidney function (hazard ratio 2.8, P  < .001). Comparing patients with AAV and kidney involvement with a matched general population, patients with AAV had poor survival outcomes, even in early stages of chronic kidney disease. The main cause of death was infection followed by cardiovascular disease in patients developing ESKD and malignancy in those who did not. Some 34% of patients with initial need for dialysis recovered kidney function after treatment. Thirty-five out of 175 in need of kidney replacement therapy (KRT) during follow-up received a kidney transplant with good outcome; there was 86% patient survival at 10 years. In the subcohort of 214 patients with available kidney biopsies, three scoring systems were tested: the Berden classification, the Renal Risk Score and the Mayo Clinic Score. The scores highlighted the importance of normal glomeruli and severe glomerulosclerosis on kidney survival (P  < .001 and P  = .001, respectively). The Renal Risk Score demonstrated a moderate prediction of kidney survival (area under the curve 0.79; standard error 0.03, 95% confidence interval 0.71–0.83). Conclusions Early diagnosis of AAV is extremely important. Even milder forms of kidney involvement have an impact on the prognosis. Patients in need of KRT had the lowest survival rates, but kidney transplantation has shown favorable outcomes for eligible AAV patients. The three histologic scoring systems were all identified as independent prognostic factors for kidney outcome. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to explore ocular manifestations in ANCA-associated vasculitis (AAV), focusing on granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA), and microscopic polyangiitis (MPA) and to examine the associations with laboratory parameters and other systemic manifestations. Methods: This retrospective study reviewed data from 533 AAV patients across two major Chinese medical centers from January 2016 to November 2023. Data including diagnosis, cranial manifestations of disease, ocular complications, and laboratory parameters were analyzed. Univariate and multivariable logistic regression analyses assessed associations across disease manifestations. Machine learning models were also utilized to predict the risk of retinal/eye involvement in AAV patients. Results: Among 533 patients (210 GPA, 217 MPA, 99 EGPA, and 7 unclassified AAV), ocular complications were observed in 20.64% of them, with a distribution of 36.67% in GPA, 7.37% in MPA, and 18.18% in EGPA. The most common ocular manifestations included scleritis and retro-orbital mass/dacryocystitis, which were notably prevalent in GPA patients. Retinal involvement was observed in 9.09% of EGPA cases. The machine learning models yielded that eosinophil percentage (EOS%), high-sensitivity C-reactive protein (hsCRP), and CD4 + T cell/CD8 + T cell ratio (T4/T8) can predict retinal involvement. Furthermore, the white blood cell, EOS%, APTT, IgA, hsCRP, PR3-ANCA, and T4/T8 can predict eye involvement. Conclusion: Ocular manifestations are a prevalent complication across all forms of AAV. Predictive models developed through machine learning offer promising tools for early intervention and tailored patient care. This necessitates a multidisciplinary approach, integrating rheumatology and ophthalmology expertise for optimal patient outcomes. Key Points • This study provides new insights into the ocular manifestations of ANCA-associated vasculitis across different subtypes, revealing a notable prevalence of ocular complications. • A machine learning model is built to predict eye/retinal involvement, enhancing early diagnostic capabilities. • The findings could guide more systematic ocular screenings in ANCA-associated vasculitis patients and influence treatment protocols. [ABSTRACT FROM AUTHOR]

Objectives: This systematic review and meta-analysis aimed to investigate the prevalence of bronchiectasis (BR) in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), the association of BR with manifestations of AAV, and the features of BR in AAV. Materials and methods: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for publications related to AAV and BR in English from January 1, 1994, until December 7, 2022. The prevalence of BR was synthesized using random-effects models, and sources of heterogeneity were assessed by sensitivity and subgroup analyses. Odds ratios (ORs) were calculated using fixed-effects models to evaluate the association of BR with manifestations of AAV. Only qualitative synthesis was performed on the features of BR. Results: Studies that reported on the prevalence (n=24), the association (n=6), and the features (n=8) of BR were identified. The pooled overall prevalence of BR among AAV was 19% (95% confidence interval [CI]: 13-27%). The prevalence of patients with myeloperoxidase (MPO)-ANCA was significantly higher than those with proteinase 3-ANCA (28% vs. 13%, p=0.01). The female sex (OR=2.41), peripheral neuropathy (OR=4.58), MPO-ANCA (OR=4.73), and microscopic polyangiitis (OR=2.72) were associated with BR in AAV. Compared to individuals without BR, AAV-BR patients exhibited relatively lower levels of proteinuria. The diagnosis of BR could follow, be concomitant to, or precede that of AAV. However, BR usually did not respond to immunosuppressive therapy. Conclusion: AAV with BR is a common condition with special manifestations. The association of BR with AAV may not be accidental; however, the underlying pathogenesis remains to be clarified. [ABSTRACT FROM AUTHOR]

Objective Granulomatosis with polyangiitis (GPA) is an ANCA-associated vasculitis. The 2022 ACR/EULAR-endorsed classification criteria for GPA was derived using data only from adult patients. We aimed to assess the performance of the ACR/EULAR classification criteria for GPA in paediatric patients and compare it with the EULAR/Pediatric Rheumatology International Trials Organization (PRINTO)/Pediatric Rheumatology European Society (PReS)-endorsed Ankara 2008 criteria for GPA. Methods Retrospective data of paediatric patients with GPA in 20 centres from 9 countries were evaluated. The diagnosis of GPA was made according to the expert opinion. The sensitivity, specificity, positive predictive value, and negative predictive value of the criteria sets were evaluated. Results The study included 77 patients with GPA and 108 controls [IgA vasculitis (n  = 44), Takayasu's arteritis (n  = 20), microscopic polyangiitis (n  = 16), polyarteritis nodosa (n  = 14), Behçet's disease (n  = 12), eosinophilic granulomatosis with polyangiitis (n  = 1) and Cogan's syndrome (n  = 1)] with a median age of 17.8 and 15.2 years, respectively. Among patients with GPA, constitutional symptoms (85.7%) and ENT involvement (79.2%) were the most common presentations. In the GPA group, 73 patients fulfilled the Ankara 2008 criteria and 69 the ACR/EULAR classification criteria. Sensitivities of the Ankara 2008 criteria and the ACR/EULAR classification criteria were 94.8% and 89.6%, while specificities were 95.3% and 96.3%, respectively. No significant difference was found between sensitivities and specificities of both classification criteria (P  = 0.229 and P  = 0.733, respectively). Conclusion In children, both the ACR/EULAR and EULAR/PRINTO/PReS Ankara 2008 classification criteria for GPA perform well and similarly. [ABSTRACT FROM AUTHOR]

Objectives Anti-neutrophil cytoplasm antibodies (ANCA)-associated vasculitides (AAV) are rare conditions characterized by inflammatory cell infiltration in small blood vessels, leading to tissue necrosis. While most patients with AAV present antibodies against either myeloperoxidase (MPO) or proteinase 3 (PR3), rare cases of dual positivity for both antibodies (DP-ANCA) have been reported, and their impact on the clinical picture remains unclear. The goal of this study was to investigate the clinical implications, phenotypic profiles and outcomes of patients with DP-ANCA. Methods A retrospective screening for DP-ANCA cases was conducted at Brest University Hospital's immunology laboratory (France), analysing ANCA results from March 2013 to March 2022. Clinical, biological, imaging, and histological data were collected for each DP-ANCA case. Additionally, a comprehensive literature review on DP-ANCA was performed, combining an artificial intelligence (AI)-based search using BIBOT software with a manual PUBMED database search. Results The report of our cases over the last 9 years and those from the literature yielded 103 described cases of patients with DP-ANCA. We identified four distinct phenotypic profiles: (i) idiopathic AAV (∼30%); (ii) drug-induced AAV (∼25%); (iii) autoimmune disease associated with a low risk of developing vasculitis (∼20%); and (iv) immune-disrupting comorbidities (infections, cancers, etc) not associated with AAV (∼25%). Conclusion This analysis of over a hundred DP-ANCA cases suggests substantial diversity in clinical and immunopathological presentations. Approximatively 50% of DP-ANCA patients develop AAV, either as drug-induced or idiopathic forms, while the remaining 50%, characterized by pre-existing dysimmune conditions, demonstrates a remarkably low vasculitis risk. These findings underscore the complex nature of DP-ANCA, its variable impact on patient health, and the necessity for personalized diagnostic and management approaches in these cases. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the study is to assess real-world, long-term safety/effectiveness of mepolizumab for eosinophilic granulomatosis with polyangiitis (EGPA) in Japan. Methods: The Mepolizumab long-term study to Assess Real-world Safety and effectiveness of EGPA in Japan (MARS) (GSK ID: 213684/NCT04551989) is an ongoing 96-week study of patients with EGPA who received four-weekly mepolizumab 300 mg subcutaneously for ≥96 weeks before study entry (baseline) and continued treatment. This interim analysis included safety from baseline to Week 48 (observation period) and clinical outcomes before mepolizumab and during the observation period. Results: Of 118 patients enrolled, 29% (34/118) experienced adverse events (AEs), of which 13% (15/118) experienced serious AEs; none were considered mepolizumab related. The median oral corticosteroid (OCS) dose decreased from 6.9 (pre-mepolizumab) to 3.0 (baseline) and 2.0 mg/day (Weeks 45–48); the proportion of patients receiving no OCS increased from 8% to 32% and 38%, respectively. Patients experiencing clinical symptoms decreased from 94% (pre-mepolizumab) to 73% (baseline) and 67% (Week 48). During the observation period, 5% of patients experienced EGPA relapse; the rates of EGPA-related hospitalisations, EGPA-related emergency room/unscheduled visits, and asthma exacerbations were 0.05, 0.09, and 0.08 event/person-year, respectively. Conclusions: The results of mepolizumab treatment for ≥144 weeks (before baseline plus observation) were consistent with the known safety profile and allowed OCS dose reduction while improving disease control versus pre-treatment among patients with EGPA. [ABSTRACT FROM AUTHOR]

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases. [ABSTRACT FROM AUTHOR]

Objectives Rituximab is used for remission induction and the prevention of relapse in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study evaluated the incidence of safety events and compared time to first serious adverse event (SAE) between a rituximab cohort and a cohort treated with non-rituximab therapies in a real-life setting. Methods Rituximab surveillance study in vasculitis was a retrospective observational study of patients with AAV who received rituximab (MabThera) or other treatments between 2003 and 2017 at a specialist vasculitis clinic. The primary endpoint was time to first SAE. Results 392 patients were enrolled: 247 in the rituximab and 145 in the control cohorts with a total follow up of 2217 person-years (mean study duration 5.7 years). Mean age was 61 years, 77% had granulomatosis with polyangiitis (GPA). There were differences in baseline characteristics (disease duration and prior immunosuppressive use) between groups. 134/247 patients (54%) in the rituximab and 58/145 (40%) of controls experienced at least one SAE. Time to first SAE was shorter in the rituximab group (hazard ratio (HR) 1.55, 95% CI 1.07–2.26, P  = 0.022). Predictors of first SAE were higher vasculitis damage index and the presence of chronic pulmonary or kidney disease. The risk of serious infection was higher in the rituximab group (relative risk (RR) 2.12, 95% CI 1.31–3.43). Conclusion Over 40% of patients with AAV experienced at least one SAE. Although shorter time to first SAE and higher risk of infection were observed in the rituximab group, baseline imbalances necessitate a careful interpretation of these results. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic necrotizing vasculitis that predominantly affects small vessels. In this report, we present a typical case of granulomatosis with polyangiitis (GPA) complicated by spontaneous renal hemorrhage (SRH), a rare but potentially severe condition. The patient developed SRH during immunosuppressive therapy but recovered following conservative treatment. We then conducted a systematic literature review on SRH in the context of AAV, and analyzed clinical features, management strategies, and patient prognosis. A total of 15 patients were enrolled for statistical analysis, comprising the one case reported in the current study and 14 from the literature. Of these patients, nine presented with GPA and six showed microscopic polyangiitis (MPA), with a sex distribution of 3:2 males to females. The average patient age was 54.5 years, and ranged from 25 to 82 years. Acute flank pain was the most common clinical manifestation, and was occasionally accompanied by anemia and shock. Treatment varied for the different patients. Eight patients received glucocorticoid and immunosuppressive agents that included rituximab, cyclophosphamide, and azathioprine; five patients underwent transcatheter arterial embolization (TAE); and one patient underwent nephrectomy. Our findings indicate that SRH typically occurs early in the course of AAV and correlates with disease activity, with renal aneurysm rupture as the primary cause. More than half of the patients respond well to corticosteroids and immunosuppressants. Timely TAE is essential for patients showing persistent deterioration despite conservative management.

Introduction: Anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV) is a rare group of systemic autoimmune diseases that primarily target small blood vessels. Renal manifestations often present as pauci-immune focal and segmental necrotizing crescentic glomerulonephritis (PI-NCGN), which can progress to acute or chronic kidney failure and multiorgan involvement. It is frequently associated with poor outcomes. We report a case of PR3-positive ANCA-associated vasculitis complicated by rapidly progressive glomerulonephritis, acute kidney injury, and diffuse alveolar hemorrhage during the COVID-19 pandemic. This case highlights the diagnostic challenges of differentiating AAV from conditions associated with SARS-CoV-2 infection, as the clinical and radiological presentations of pulmonary-renal syndromes may overlap. The findings underscore the importance of maintaining a comprehensive differential diagnosis in patients with pulmonary and renal involvement, particularly in the post-COVID-19 era, to ensure timely and accurate management of rare autoimmune conditions such as AAV. Conclusion: ANCA-associated vasculitis (AAV) remains a diagnostic and therapeutic challenge, particularly in the post-COVID-19 era, where overlapping clinical and radiological features with SARS-CoV-2 complications can obscure timely identification. This case highlights the critical importance of maintaining a broad differential diagnosis in patients presenting with pulmonary-renal syndromes to differentiate AAV from more common conditions associated with COVID-19.

Granulomatosis with polyangiitis, a rare autoimmune disease affecting organs such as the respiratory system, kidneys, and lungs, poses unique challenges in pregnancy. A 25-year-old woman with chronic liver disease, vasculitis, protein C and S deficiency, hypothyroidism, and gestational diabetes presented at 24 weeks gestation with shortness of breath, fever, and vomiting. Her thrombocytopenia was managed with transfusions, and regular prenatal ultrasounds were conducted. At 36 weeks, an elective cesarean delivered a healthy 2.4 kg baby. This case highlights the critical role of multidisciplinary care in achieving favorable outcomes in complex pregnancies affected by granulomatosis with polyangiitis.

BackgroundGlecaprevir/pibrentasvir is an effective antiviral therapy for hepatitis C virus infection and is generally regarded safe in patients with renal impairment. However, renal complications are a notable, albeit rare, concern.Case presentationWe report a case of acute kidney injury in a man in his 50s with chronic hepatitis C virus, chronic obstructive pulmonary disease, morbid obesity, a history of heroin dependence, and untreated type 2 diabetes mellitus. About four weeks into an eight-week glecaprevir/pibrentasvir regimen he developed progressive lower extremity edema, bullae, and skin ulcers with worsening renal function. His serum creatinine rose to 4.46 mg/dL and blood urea nitrogen to 44 mg/dL. ANCA serology revealed dual perinuclear and cytoplasmic positivity, though anti-proteinase 3 and anti-myeloperoxidase antibody tests were negative. Kidney biopsy revealed diffuse tubulointerstitial injury with erythrocyte casts indicative of glomerular bleeding into the distal nephrons, though without glomerular crescent formation.ConclusionThis case illustrates the potential for glecaprevir/pibrentasvir to induce acute kidney injury, acute interstitial nephritis and possibly ANCA-associated vasculitis. Recognizing these adverse renal effects is critical for making timely diagnosis and management in hepatitis C virus patients undergoing antiviral therapy.

This report primarily describes a rare case of an elderly male patient who initially presented with central retinal artery occlusion (CRAO) in the left eye and was ultimately diagnosed with anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis involving the eyes, gastrointestinal tract, and kidneys. However, due to irregular treatment, both eyes developed progressive ocular manifestations later. This article emphasizes the importance of actively screening for and treating underlying conditions in cases of CRAO. A comprehensive assessment of the patient’s medical history, systemic condition, and ocular examination can aid in early diagnosis, slow disease progression, and reduce mortality.

Background: Although many chronic inflammatory conditions are linked to elevated cardiovascular risk, the specific extent of this risk in ANCA-associated vasculitis (AAV) remains elusive, largely due to the disease's rarity. Our study sought to clarify the cardiovascular risks and mortality linked to AAV. Methods: A systematic literature review was conducted across multiple databases from their inception until April 2024 to identify studies comparing cardiovascular outcomes in patients with and without AAV. R Studio's meta package was used to pool risk ratios under the random-effects model, and statistical significance was set at p

Antineutrophilic cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a condition characterized by vessel inflammation and may have a variety of etiologies. Among these, cocaine and its common adulterant, levamisole, have been described to contribute to the development of AAV with distinct cutaneous manifestations. Classically, these manifestations involve purpuric or necrotic lesions involving the ears, nose, and extremities. However, we present a case of cocaine‐induced AAV presenting with violaceous nodules on the dorsal hands in order to demonstrate that this condition may not always present with retiform purpura and skin necrosis. [ABSTRACT FROM AUTHOR]

The article discusses the use of rituximab as an induction therapy for ANCA-associated vasculitis (AAV) in the Asia Pacific region. AAV is a group of vasculitides that can lead to organ failure and mortality if left untreated. Studies have shown that rituximab is non-inferior to cyclophosphamide (CYC) in treating AAV, with potential superiority in certain patient subgroups. While rituximab may be more effective in patients with relapsing disease and positive anti-PR3 ANCA subtype, there is still a need for more data on its efficacy and tolerability in Asian populations with AAV. The availability of rituximab biosimilars has made the treatment more accessible, but cost-effectiveness remains a concern in the Asia Pacific region. [Extracted from the article]

Antineutrophil cytoplasmic antibodies associated vasculitis (ANCA-AV) is a systemic necrotizing granulomatous vasculitis affecting mainly small-caliber vessels. ANCA-AV occupy a special place among systemic vasculitis, which is characterized by a highly active life-threatening course of the disease, requiring rapid differential diagnosis and aggressive immunosuppressive therapy. The ANCA-AV group consists of 3 nosologies: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis and microscopic polyangiitis. The “calling card” of ANCA-AV is the lesion of the upper respiratory tract, especially the ENT organs (70–100 % of patients). The nasal cavity and paranasal sinuses are the most common areas of lesion in the head and neck (85–100 %), whereas ear damage occurs in about 35% (range, 19–61 %) of cases. Lesion of the ENT organs is typical for the debut of ANCA-AV, which makes early diagnosis difficult, since diseases of the upper respiratory tract are extremely common in all age groups. Diagnosis verification occurs mainly at the stage of generalized involvement of many organs and systems, causing severe course with the development of pulmonary-cardiac and renal insufficiency, which lead to the death of the patient. The main ENT manifestations of ANCA-AV can be grouped into several groups: sinonasal, otological, tracheobronchial, oral cavity lesions and others. Pseudotumors are often found in ANCA-AV. They are characterized by the appearance of parapharyngeal, parotid, submandibular, paratracheal volumetric formations. As a rule, the appearance of tumor-like formations is observed at an early stage of the disease and is associated with the presence of antibodies to proteinase 3, systemic manifestations of vasculitis. Pseudotumor in the ENT region may be accompanied by secondary neuropathies of cranial nerves, destruction of bone tissue, which requires histological verification of the disease.

Objective: To describe the clinical profile and predictors of mortality of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients in Hong Kong. To compare the accuracy of the latest Five-Factor Score (FFS-2009) and the Birmingham Vasculitis Activity Score (BVAS) in prediction of survival with this local cohort. Methods: A retrospective observational study on newly diagnosed AAV patients, from January 1, 2011 to March 31, 2022, managed in the Kowloon West Cluster (KWC) hospitals in Hong Kong. Demographic and baseline characteristics, clinical profile, and treatment profile were reviewed. Factors associated with mortality were analyzed with the Cox proportional hazards model. The performances of FFS and BVAS in mortality prediction were analyzed by receiver operating characteristic (ROC) curves. Results: A total of 83 AAV patients were included in the study. The median age was 70.5 years at diagnosis. Microscopic polyangiitis (MPA; 69.9%) was the most common AAV subtype. The median FFS and BVAS were 2 and 20, respectively. The overall mortality was 45.6% across the study period. Multivariate Cox regression identified age at diagnosis (HR 1.043, [Formula: see text]), stabilized peak serum creatinine (HR 1.002, [Formula: see text]), hemoglobin level (HR 0.754, [Formula: see text]), cardiac involvement (HR 3.862, [Formula: see text]), and use of maintenance therapy (HR 0.261, [Formula: see text]) as independent predictors of overall survival. Both FFS and BVAS were significant predictors of overall survival. The areas under the curve (AUC) of ROC curves suggested FFS was a good prediction tool for early mortality in 1 year, with an AUC value of 0.874. Conclusion: Despite the advances in treatment, AAV still carried significant morbidities with high mortality. Clinical predictors and existing scoring systems showed good predictive power on mortality.

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

Objective: Functional magnetic resonance imaging (fMRI) has been applied to assess the microstructure of the kidney. However, it is not clear whether fMRI could be used in the field of kidney injury in patients with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: This study included 20 patients with AAV. Diffusion kurtosis imaging (DKI) and blood oxygen level-dependent (BOLD) scanning of the kidneys were performed in AAV patients and healthy controls. The mean kurtosis (MK), mean diffusivity (MD), and fractional anisotropy (FA) parameters of DKI, the R2* parameter of BOLD, and clinical data were further analyzed. Results: In AAV patients, the cortex exhibited lower MD but higher R2* values compared to the healthy controls. Medullary MK values were elevated in AAV patients. Renal medullary MK values showed a positive correlation with serum creatinine levels and negative correlations with hemoglobin levels and estimated glomerular filtration rate. To assess renal injury in AAV patients, AUC values for MK, MD, FA, and R2* in the cortex were 0.66, 0.67, 0.57, and 0.55, respectively, and those in the medulla were 0.81, 0.77, 0.61, and 0.53, respectively. Conclusions: Significant differences in DKI and BOLD MRI parameters were observed between AAV patients with kidney injuries and the healthy controls. The medullary MK value in DKI may be a noninvasive marker for assessing the severity of kidney injury in AAV patients.

This case report presents a complex case of a 65-year-old female with a history of hypertension and a family history of polycystic kidney disease and Fabry disease presented with acute pancreatitis and subsequent renal insufficiency. Despite initial corticosteroid therapy for immuno-allergic nephropathy, the patient’s condition deteriorated with the development of a skin rash, uremic syndrome, and neurological symptoms. A renal biopsy revealed cellular crescents and cytoplasmic vacuolization in podocytes and tubular cells. Genetic testing confirmed a GLA gene mutation, consistent with Fabry disease. While undergoing treatment with cyclophosphamide, the patient experienced severe allergic reactions, ultimately leading to acute respiratory distress syndrome and fatal outcome. Despite the Fabry disease variant being primarily associated with cardiac involvement, renal involvement was evident. This case highlights the rarity of this co-occurrence, the diagnostic challenges, the importance of genetic factors in autoimmune kidney diseases, and the impact of drug allergies on patient management.

Objective: This study aimed to identify plasma biomarkers that are significantly altered in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and are closely associated with AAV disease activity, as well as to explore their role in the pathogenesis of AAV. Methods: Cytokines were measured using Human Immune Response Panel 80-Plex in plasma from 59 patients with AAV and 20 healthy controls (HCs). The differentially expressed cytokines between the two groups and the possible signaling pathway involved in the pathogenesis of AAV were analyzed by bioinformatics. Relationship analysis was performed between these cytokines and clinical parameters to identify the biomarkers that can effectively indicate disease activity. Results: We identified 65 differentially expressed cytokines between the two groups. Among them, 43 cytokines significantly affected the risk of AAV. Bioinformatic analysis showed that the 43 cytokines were primarily enriched in signaling pathways such as cytokine-cytokine receptor interaction, viral protein interaction with cytokine and cytokine receptor, chemokine signaling pathway, and IL-17 signaling pathway. The levels of 25 cytokines were significantly positively correlated with Birmingham Vasculitis Activity Score (BVAS), and the levels of 2 cytokines were significantly negatively correlated with BVAS. Receiver operating characteristic analysis showed that 9 cytokines can distinguish between disease relapse and remission (PTX3: area under curve (AUC)=0.932, IL34: AUC=0.856, IL2RA: AUC=0.833, CCL23: AUC=0.826, VEGFA: AUC=0.811, TNFSF13: AUC=0.795, Granzyme A: AUC=0.788, CSF3: AUC=0.773 and IL1A: AUC=0.765). The elevated levels of these 9 cytokines suggested a risk of disease relapse. The AUC of CCL11 in disease relapse and remission was 0.811 (p=0.0116). Unlike the other 9 cytokines, a negatively association existed between CCL11 level and the risk of disease relapse. Conclusion: A group of cytokines that may be involved in AAV pathogenesis was identified. Increased PTX3, IL34, IL2RA, CCL23, and VEGFA levels correlatewith active disease in AAV and may be used as biomarkers to identify the disease relapse of AAV. [ABSTRACT FROM AUTHOR]

Introduction The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. Methods We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. Conclusion The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV. [ABSTRACT FROM AUTHOR]

Background The anti-neutrophil cytoplasmic antibody (ANCA) renal risk score (ARRS) for predicting renal survival in ANCA-associated vasculitis (AAV) had not previously been validated in adults over 65 years of age and presenting impairments associated with an aging kidney, a high cardiovascular comorbidity burden and prevalent microscopic polyangiitis. Methods We retrospectively studied a cohort of 192 patients over 65 years of age [median (interquartile range) age: 73 (68–78) years], including 17.2% with renal-limited vasculitis, 49.5% with microscopic polyangiitis and 33.3% with granulomatosis with polyangiitis, at six centres in northern France. The primary study endpoint was the cumulative incidence of end-stage kidney disease (ESKD, maintenance of dialysis for at least 3 months) at 12 months, with death considered as a competing event. Results The median serum creatinine concentration at diagnosis was 300 (202–502) µmol/L, and 48 (25.0%) patients required dialysis at presentation. The ARRS was high in 43 (22.4%) patients, medium in 106 (55.2%) and low in 43 (22.4%). The cumulative incidence of ESKD at 12 months was 0% in the low-risk group, 13.0% (interquartile range 7.6–20.0) in the medium-risk group and 44.0% (29.0–58.0) in the high-risk group (P <.001). In the subgroup of 149 patients presenting a medium or high score, the ARRS had a C-index of 0.66 (0.58–0.74) for the prediction of ESKD at 12 months; this rose to 0.86 (0.80–0.90) when dialysis status at diagnosis was included. Conclusion The ARRS was a poor predictor of kidney survival at 12 months among patients over 65 years of age with renal AAV involvement—especially in the high ARRS group. The addition of dialysis status at diagnosis as an additional clinical parameter might improve the predictive performance of the ARRS. [ABSTRACT FROM AUTHOR]