The incidence of vasculitides in Israel from 2007 to 2021 and during the COVID-19 pandemic.

Background: The incidence of various types of vasculitis conditions over time, specifically during coronavirus disease 2019 (COVID-19), is unknown. Objectives: We aimed to assess recent trends in vasculitides and the effect of the COVID-19 pandemic on these trends. Design: We conducted a retrospective analysis of Israel's largest Health Maintenance Organization, which covers over 4.7 million patients and represents 55% of the country. Methods: We calculated the age- and sex-adjusted incidence of giant cell arteritis (GCA), Takayasu, ANCA-associated vasculitis (AAV), IgA vasculitis, cryoglobulinemia, and Behcet's disease (BD) during 2007-2021. We analyzed associations of COVID-19 with the incidence of each of the examined conditions. Results: During 2007-2021, the adjusted annual incidence decreased from 7.9 (95% confidence interval (CI) 3.5-17.9) to 1.5 (95% CI 0.7-3.6) per 100,000 for GCA, from 5.2 (95% CI 2.7-11.1) to 1.5 (95% CI 0.7-3.3) per million for IgA vasculitis, and from 6.3 (95% CI 3.0-13.5) to 1.0 (0.5-2.5) per 100,000 for BD. The relative risks for these conditions decreased: 0.92 (95% CI 0.91-0.93), 0.93 (95% CI 0.89-0.98), and 0.90 (95% CI 0.85-0.94), respectively. The incidences of Takayasu, AAV, and cryoglobulinemia remained unchanged. The COVID-19 pandemic was not associated with changes in the incidence of any examined vasculitides. Conclusion: The incidences of GCA, IgA vasculitis, and BD decreased substantially in Israel during 15 years and were unaffected by the COVID-19 pandemic. Future studies should focus on possible environmental contributions to these findings.

Bowel and Small Joint Involvement in Granulomatosis With Polyangiitis: A Case Report.

We discuss the case of a 45-year-old male with complaints of abdominal pain, loose stools with on and off melena, and multiple joint pains bilaterally. The patient reported having similar episodes in the past, with slight variations in the symptoms and relief with short courses of steroids. Initially, a workup was done to identify an infectious etiology of the diarrhea. However, no such cause was identified. Similarly, an autoimmune profile was ordered to investigate the patient's joint complaints, albeit with no conclusive findings. His renal function tests and urinalysis showed findings indicative of an acute kidney injury. This prompted an antineutrophil cytoplasmic antibody (ANCA) profile, which was positive for c-ANCA. A diagnosis of granulomatosis with polyangiitis (GPA) was made, and the patient was started on pulse steroid and immunomodulator therapy with improvement in the patient's condition. This case is atypical due to its involvement of the gastrointestinal system, which is relatively rare, as well as polyarthritis of the small joints.

Seven cases illustrating difficulties in the treatment of MPO-ANCA-positive refractory otitis media.

There are increasing reports of patients with refractory otitis media caused by anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), especially myeloperoxidase (MPO)-ANCA-positive middle ear disease.　However, making a definitive diagnosis can be difficult, which can adversely affect the outcome of treatment.　We reviewed the diagnostic features of MPO-ANCA-positive middle ear disease and here discuss the difficulties of timely diagnosis and treatment.　Seven cases were eligible (6 women, 1 man;aged 57-83 years), and all were MPO-ANCA positive and proteinase 3 (PR3)-ANCA negative.　The patients were referred to our institution for management of intractable otitis media (2/7), progressive hearing loss (7/7) with facial palsy (1/7), and/or a high MPO-ANCA titer (5/7).　All patients underwent tapering steroid therapy and their MPO-ANCA titer was monitored.　Refractory MPO-ANCA-positive otitis media was noted:5 of 7 cases showed improvement with tapering steroid therapy but cure was not achieved in the remaining 2 cases.　This study demonstrates the difficulties in the diagnosis and treatment of localized AAV.　Early diagnosis and treatment can improve the prognosis of patients with AAV but global diagnostic criteria for ear disease have not been established.　Additional cases should be prospectively examined to establish a treatment for MPO-ANCA-positive middle ear disease.

Acute Renal Failure and Generalized Weakness in a 75-Year-Old Male With Pauci-Immune Necrotizing Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Case Report.

We describe a 75-year-old male who presented to the emergency department with generalized weakness and was ultimately diagnosed with acute renal failure secondary to pauci-immune necrotizing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The patient's clinical course was complicated by a perforated gastric ulcer and severe malnutrition, necessitating involvement from multiple specialists. The case highlights the challenges of this rare vasculitis and the complications that can arise from the disease and its treatment. .

Indian Rheumatology Association guidelines for the management of ANCA associated vasculitis.

BACKGROUND: The ACR in 2021 and the EULAR in 2022 published recommendations for management of ANCA-associated vasculitis. Given the differences in the demographic, clinical profiles, and the socio-economic realities between various countries, there is a need for development of guidelines for the management of AAV for less economically developed regions of the world. METHODS: These guidelines were made following the GRADE methodology. After the systematic literature review, recommendations were formulated and opinion was sought from the 18-member expert panel consisting of 17 clinicians and one patient representative. RESULTS: Twenty recommendations were formulated. We recommend ANCA testing by ELISA over IIF. For remission induction in active GPA or MPA, we recommend use of intravenous cyclophosphamide or rituximab in combination with glucocorticoids. We conditionally recommend the use of reduced dose glucocorticoids over standard dose glucocorticoids for remission induction in active GPA or MPA. For remission maintenance in patients with GPA or MPA, we recommend the use of rituximab over azathioprine for at least 48 months from diagnosis. We conditionally recommend the use of plasma exchange in patients with severe renal vasculitis. For remission induction in EGPA, we recommend use of cyclophosphamide or rituximab in severe disease and mepolizumab or azathioprine or methotrexate or mycophenolate mofetil in non-severe disease. CONCLUSIONS: These are the first ever Indian recommendations for the management of AAV. Despite our effort to formulate these recommendations based on high quality evidence, some recommendations were still based on low quality evidence but with high rate of agreement among expert panel members.

ANCA-associated vasculitis and lung cancer: an immunological perspective.

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.

Effective management of necrotizing crescentic glomerulonephritis using an aggressive combination therapy including avacopan in a patient double-seropositive for anti-GBM antibodies and ANCA: a case report.

The prognosis of anti-glomerular basement membrane (anti-GBM) nephritis, often accompanied by the presence of antineutrophil cytoplasmic antibodies (ANCA), is poor, and even with aggressive therapeutic approaches, kidney replacement therapy (KRT) is typically required. Here, we present a case of necrotizing crescentic glomerulonephritis in a patient double-seropositive for anti-GBM antibodies and ANCA who successfully achieved dialysis independence following aggressive treatment, including avacopan. The patient was a 77-year-old woman with rapidly progressive glomerulonephritis and double seropositivity for myeloperoxidase-ANCA and anti-GBM antibodies. A kidney biopsy revealed diffuse cellular crescents with necrosis and immunoglobin (Ig)G1 and IgG3 positivity on immunofluorescence staining, leading to a histological diagnosis of anti-glomerular basement membrane nephritis. Our treatment approach involved a novel combination of glucocorticoids, rituximab, low-dose cyclophosphamide, and plasma exchange complemented by avacopan. Temporary hemodialysis was required, and the patient successfully discontinued dialysis after 12 sessions despite a poor histological prognosis. This case underscores the significance of considering aggressive therapeutic strategies, including avacopan, for severe anti-GBM nephritis, even in the absence of lung involvement, to avert the need for KRT.

Hydroxychloroquine as an add-on therapy for the induction therapy of MPO-AAV: a retrospective observational cohort study.

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.

Characteristic changes in the mRNA expression profile of plasma exosomes from patients with MPO-ANCA-associated vasculitis and its possible correlations with pathogenesis.

To explore the expression patterns and potential roles of mRNAs in exosomes from patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (MPO-AAV). Plasma exosomes were isolated from MPO-AAV patients and healthy controls (HCs) to screen for differential mRNA expression via exosomal mRNA sequencing. The differentially expressed mRNAs in exosomes from the 2 groups were comparatively explored by bioinformatics analysis. The six most differentially expressed mRNAs were selected and validated in larger groups of MPO-AAV patients and HCs by real-time quantitative polymerase chain reaction (RT‒qPCR). The relationships between these selected mRNAs and patient characteristics were statistically analyzed. Compared with HCs, a total of 1077 mRNAs in exosomes from MPO-AAV patients were found to be significantly upregulated, including DEPDC1B and TPST1, while NSUN4 and AK4 were significantly downregulated. Statistical analysis did not reveal any correlation between the six selected mRNAs and clinical indicators, including disease activity. GO enrichment analysis revealed that these differentially expressed genes participate in various enzyme activities, protein synthesis, etc. KEGG pathway analysis revealed that metabolic pathways, cell adhesion molecules, epithelial signaling, and mitogen-activated protein kinase (MAPK) signaling pathways were significantly enriched in the exosomal mRNAs. There were significant differences in the expression of exosomal mRNAs between MPO-AAV patients and HCs, which may be related to the occurrence and development of MPO-AAV. These findings provide clues for further investigations of MPO-AAV pathogenesis and the identification of new potential therapeutic targets.

Superiority of Avacopan and Mepolizumab to Glucocorticoid Tapering in the Treatment of Anti-neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis: A Systematic Review.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises a spectrum of autoimmune diseases, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). Studies have shown that avacopan and mepolizumab are promising therapeutics for partial or complete replacement of glucocorticoids (GC), with sustained remission while completely weaning off GC. Avacopan inhibits C5aR in the complement pathway, preventing neutrophil migration, while mepolizumab targets IL-5R, reducing eosinophil activity. Additionally, complement inhibition has not only contributed to the recovery of renal function and alleviation of physical symptoms but has also enhanced patients' overall quality of life and mental well-being. This systematic review explores the pathogenesis of AAV, traditional treatments, and the potential of emerging complement and interleukin antagonist therapies such as avacopan and mepolizumab in revolutionizing AAV management.

Immunoadsorption and Plasma Exchange are Comparable in Anti-Neutrophil Cytoplasmic Antibodies or Anti-Glomerular Basement Membrane Removal Kinetics.

Introduction: Apheresis allows the fast removal of autoantibodies in anti-glomerular basement membrane (anti-GBM) disease, and in severe antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. The CINEVAS study tested whether immunoadsorption (IA) allowed a faster removal of ANCA and/or anti-GBM antibodies than plasma exchanges (PEx). Methods: CINEVAS was a prospective multicenter study comparing IA to PEx in consecutive patients with ANCA and/or anti-GBM vasculitides. The primary objective was the reduction rate in autoantibody titers between the beginning of the first and the end of the seventh apheresis session. Secondary objectives were number of sessions needed to obtain desired reduction rates; reduction rates of total Ig levels; tolerance of sessions; and patients' outcome. Results: The results of 38 patients (16 treated with IA and 22 with PEx), and 43 autoantibodies, were analyzed. There was no difference in the reduction rates in autoantibody titers between IA and PEx over 7 sessions (respectively 98% vs. 96%, P = 0.39). The numbers of sessions needed to obtain undetectable autoantibodies, or 50%, 75%, or 90% reductions, did not differ between techniques. Greater reduction rates of autoantibodies were observed when plasma was separated by filtration compared to centrifugation, with IA and PEx. IA allowed a greater reduction in total IgG levels, and better preservation of total IgA and IgM levels than PEx. PEx sessions required higher volumes of plasma, IA sessions higher volumes of citrate; IA sessions were longer. Conclusions: IA and PEx were comparable in ANCA or anti-GBM removal kinetics, despite a faster reduction in total IgG with IA.

Myeloperoxidase Anti-Neutrophil Cytoplasmic Antibody (MPO-ANCA)-Associated Vasculitis With Rare Clinical Manifestations After SARS-CoV-2 Multisystem Inflammatory Syndrome in a 14-Year-Old Boy.

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) microscopic polyangiitis is a rare but life-threatening small vessel vasculitis in childhood that affects multiple systems. Emerging clinical evidence suggests a possible association between SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) as well as the futuredevelopment of autoimmune diseases. A 14-year-old boy with a diagnosis of MIS-C two years prior to presentation was admitted to our hospital due to edema and left lower limb joint pain along with concomitant upper surface petechia. The patient had a positive higher SARS-CoV-2 IgG than MIS-C diagnosis titers and MPO-ANCA-positive antibody titers. Kidney biopsy favored a pauci-immune crescentic glomerulonephritis. Restrictive lung disease with concomitant diffusion abnormalities was also observed. Pancreatitis and gastrointestinal wall edema were additional clinical manifestations. SARS-CoV-2 breakthrough infection and MIS-C could contribute to the onset of autoimmune vasculitis through various immunological mechanisms. Further research is still needed to elucidate the role of SARS-CoV-2 in the pathophysiology of newly diagnosed autoimmune vasculitis.

Impact of Rituximab on Remission Rates in Granulomatosis With Polyangiitis: A Systematic Review.

This systematic review evaluates the efficacy of rituximab in inducing and maintaining remission in patients with granulomatosis with polyangiitis (GPA). We conducted a comprehensive search across multiple databases, identifying 81 studies, of which 11 met our inclusion criteria after rigorous screening and assessment for relevance and quality. Our analysis shows that rituximab, compared to traditional treatments such as cyclophosphamide and azathioprine, significantly improves remission rates and reduces relapse frequency in GPA patients. Notably, rituximab's benefits extend across various patient demographics, including pediatric groups, and are evident in different dosing regimens, highlighting its versatility and potential as a first-line therapy. The review also underscores the importance of personalized medicine approaches in managing GPA, as rituximab's effectiveness was particularly pronounced in patients with relapsing disease forms. Future research should focus on long-term outcomes, optimal dosing strategies, and the economic implications of widespread rituximab use in clinical practice. Our findings advocate for the integration of rituximab into standard treatment protocols for GPA, offering new hope for patients afflicted with this challenging autoimmune disorder.

Female With Hypertensive Emergency Later Found to Have ANCA-Associated Vasculitis: A Case Report.

Granulomatosis with polyangiitis (GPA) is a form of ANCA-associated vasculitis characterized by necrotizing vasculitis affecting small blood vessels. The clinical presentation varies based on organ involvement, commonly affecting the upper and lower respiratory tracts and kidneys. Typical GPA presents as recurrent sinus infection, otitis media, dyspnea, chest pain, and glomerulonephritis, which can present as hematuria, proteinuria, and elevated serum creatinine. ANCA tests positive in the majority of cases. Treatment strategies involve induction of remission and maintenance therapy. We report a case of a 48-year-old female presenting with a hypertensive emergency, a rarely reported manifestation of GPA. She initially presented with severe headache and cough, with systolic blood pressure exceeding 220 mmHg, necessitating hospital admission. The initial workup revealed elevated serum creatinine and CT chest findings suggestive of multi-lobar pneumonia, for which she received antibiotic treatment. Despite aggressive antihypertensive therapy, her blood pressure remained refractory, and she developed hematuria and anemia, requiring a blood transfusion. Further evaluation revealed a history of joint pain, recurrent sinus infections, and a pruritic skin rash, prompting suspicion of vasculitis. Further work-up included elevated erythrocyte sedimentation rate (ESR), normal IgE, absence of eosinophilia, and positive PR3 antibodies and c-ANCA. Prompted by clinical suspicion, treatment with steroids was initiated, and a kidney biopsy confirmed acute necrotizing pauci-immune glomerulonephritis consistent with GPA. Subsequently, rituximab therapy was initiated, resulting in significant improvement in her clinical symptoms and blood pressure, and the patient was successfully discharged home. This case highlights a rare presentation of GPA as a hypertensive emergency, possibly linked to renal involvement in the form of glomerulonephritis. Pulmonary manifestations mimicking infections posed diagnostic challenges. Cutaneous findings potentially associated with increased joint and renal involvement underscore the clinical complexity of GPA. The unusual presentation of hypertensive emergency in young patients underscores the need for heightened awareness of this potential manifestation in GPA. Early recognition and aggressive immunosuppressive therapy are crucial to mitigate irreversible renal damage in such atypical presentations.

Skin, Heart, and CNS Involvement in Granulomatosis With Polyangiitis: A Case Report.

We discuss the case of a 60-year-old male who presented with ankle pain, a necrotic rash, and progressive weakness in both lower limbs and the right upper limb. An infectious workup of the skin lesions came back negative. Additionally, his kidney function tests indicated an acute kidney injury. This prompted investigations for vasculitis etiologies, which revealed a positive cytoplasmic antineutrophil cytoplasmic autoantibody (c-ANCA). His neurological deficits were also investigated, and imaging suggested embolic infarcts. Cardiac imaging showed valve vegetations and blood culture showed a lack of growth suggestive of a noninfective nature of these lesions. Based on all these findings, a kidney biopsy was obtained and demonstrated pauci-immune segmental vasculitis consistent with ANCA-associated glomerulonephritis. As such, the patient showed improvement with heavy pulse steroid and immunomodulator therapy. Although skin, heart, and CNS involvement have been previously reported with ANCA-associated vasculitis, it is rare, especially together, and can prove a diagnostic challenge. Therefore, it is important to consider vasculitis etiology in patients presenting similarly. In addition, this case highlights the overlapping clinical picture between infective endocarditis and vasculitis with valvular involvement, making differentiation between the two challenging.

Immune landscape in the glomerular transcriptome of nephrotic syndrome and anca-associated vasculitis.

BACKGROUND: ANCA-associated vasculitis (AAV), and nephrotic syndrome encompassing diseases including minimal change disease (MCD), focal and segmental glomerulosclerosis (FSG), membranous nephropathy (MN), remain a challenge due to their varied immunological characteristics. Recent therapeutic advancements have highlighted the importance of understanding these diseases' immunological landscapes. METHODS: This study analyzed transcriptomics data from renal glomerular tissues of patients with AAV, FSG, MCD, MN, and normal controls. Utilizing an immune-related gene set of 883 genes, methods including Gene Set Variation Analysis (GSVA), LASSO regression, and Weighted Correlation Network Analysis (WGCNA) were used. Predictions of immune cell compositions were made through CIBERSORT, TIMER, MCPcounter, and quanTIseq algorithms. RESULTS: The study revealed distinct immunogenetic pathways enriched in each disease: hematopoietic cell lineage in ANCA, linoleic acid metabolism in FSG, PPAR signaling in MCD, and drug metabolism in MN. Classifiers based on immune gene expression showed high accuracy (AUC: ANCA 0.812, FSG 0.99, MCD 1, MN 0.888). Co-expression modules and PPI networks highlighted unique pathways for each disease. Predictions of immune cell composition showed elevated macrophages in FSG and MN, with Treg levels elevated across all four diseases compared to normal controls and highest in FSG. Correlation analyses demonstrated significant associations between classifier scores and immune cell types. CONCLUSION: This study offers accurate classifiers for AAV, FSG, MCD, and MN, and reveals distinct immunological pathways. These findings advance personalized treatments and highlight potential therapeutic targets in AAV and nephrotic syndrome. Further research should validate these results for clinical applications.

Early skeletal muscle manifestations in polyarteritis nodosa and ANCA-associated vasculitis.

Skeletal muscle involvement is common in patients with small- and medium-sized vasculitis, particularly polyarteritis nodosa (PAN) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Despite being not included in the standard classification criteria for PAN and AAV, skeletal muscle involvement is an important clinical indicator, particularly when vasculitic myopathy is the only pathological evidence in the absence of other organ involvement. Herein, we comprehensively reviewed and compared the clinical features of 71 and 135 patients with PAN and AAV, respectively, with skeletal muscle involvement at the time of disease onset. Most patients with PAN and AAV exhibited skeletal muscle involvement, often characterized by myalgia and occasional muscular weakness, predominantly in the lower extremities. Myalgia and weakness were observed more frequently in the distal lower extremities in patients with PAN than in those with AAV. In contrast, skeletal muscle involvement tended to exhibit a more dispersed distribution across all four extremities in those with AAV. Muscle magnetic resonance imaging T2-weighted and short-tau inversion recovery sequences can effectively identify hyperintense areas attributed to hypervascularity of affected muscle tissues and serve as a sensitive and useful modality for visually determining the suitable biopsy site. >90% of patients with PAN and AAV demonstrated perivascular inflammation in their affected muscle tissues, whereas fibrinoid necrosis of the vessel walls was reported in two-thirds of patients. Serum creatine kinase (CK) levels were within the normal range in approximately 80% of patients presenting with skeletal muscle involvement in PAN and AAV. Furthermore, muscle fiber damage was milder in patients with skeletal muscle involvement in PAN and AAV than those with idiopathic inflammatory myositis. Meanwhile, serum CK levels were elevated in 65-85% of patients with PAN and AAV who had myofiber necrosis and degeneration in the affected muscles. Most patients with PAN and AAV showed improvement in skeletal muscle involvement following glucocorticoids (GCs) administration; however, relapse was observed in some patients during the tapering of GCs. In summary, skeletal muscle involvement is a potential indicator for establishing PAN and AAV diagnoses during the early phases of the disease.

Effectiveness and safety of rituximab in severely relapsed antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective analysis of a Japanese multicentre cohort from the J-CANVAS.

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.

Cardiovascular risk in ANCA-associated vasculitis: Monocyte phenotyping reveals distinctive signatures between serological subsets.

BACKGROUND AND AIMS: Anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV. METHODS: A cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes. RESULTS: Monocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV. CONCLUSIONS: These findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV.