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Objective ANCA-negative granulomatosis with polyangiitis (GPA) remains a diagnosis of exclusion. Clinical differences between patients with ANCA-negative vs ANCA-positive GPA have not been analysed in sizable case-control studies, and the effects of ANCA-seroconversion from negative to positive are not well documented. Methods A single-centre, sex and age matched case-control study evaluated ANCA-negative vs ANCA-positive GPA from 1 January 1996 to 31 December 2015. Patients who experienced seroconversion were the subject of a case-crossover study. Clinical data and outcomes were retrieved from electronic medical records. Results ANCA-negative GPA was identified in 110 patients; 65% were female; median age was 55 (IQR 39–65) years at time of diagnosis. Disease severity was milder in ANCA-negative GPA (BVAS/WG = 2 vs 6, P  < 0.001). Mucous membranous/eye manifestations were more frequent in ANCA-negative GPA. General symptoms, pulmonary and renal involvement were more frequent in ANCA-positive GPA. Patients with ANCA-positive GPA relapsed more over 60 months (21.8% vs. 9.1%, P =  0.009) compared with ANCA-negative GPA and had shorter time to event (P =  0.043). Patients with general manifestations, BMI > 30kg/m2 and necrotizing granulomatous inflammation were more likely to relapse. The 16 patients who seroconverted into ANCA-positive during follow-up had higher mean BVAS/WG at time of diagnosis (P <  0.001) and increased incidence of relapses (P =  0.004) after seroconversion. Necrotizing granulomatous inflammation on biopsy in ANCA-negative GPA patients was identified as a risk factor for subsequent seroconversion to ANCA-positivity. Conclusion Patients with ANCA-negative GPA have milder disease and a lower frequency of relapse than those with ANCA-positive GPA. ANCA appearance portended higher disease severity and an increased frequency of relapses. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the frequency and the clinical relevance of thyroid disease in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients. Methods: A total of 305 AAV patients admitted to the Second Affiliated Hospital of Chongqing Medical University between October 2010 and December 2023 were analyzed. Demographic, clinical, and laboratory data were compared between AAV patients with and without thyroid disease. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with thyroid disease in AAV patients. Results: Among the 305 AAV patients, 52 (17.0%) had concurrent thyroid disease. In univariate analysis, gender, coronary artery disease, renal involvement, anti-Ro/SSA antibodies, anti-Ro52 antibodies, anti-thyroglobulin antibodies (TgAb), and anti-thyroid peroxidase antibodies (TPOAb) exhibited significant differences between AAV patients with and without thyroid disease (P < 0.05). Multivariate analysis revealed that female gender (odds ratio (OR) = 2.423, 95% confidence interval (95% CI) 1.241, 4.729; P = 0.009), concurrent coronary artery disease (OR = 2.998, 95% CI 1.280, 7.019; P = 0.011), and positive anti-Ro/SSA antibodies (OR = 4.697, 95% CI 1.960, 11.257; P = 0.001) were associated with thyroid disease in AAV patients. Conclusion: AAV patients have a higher incidence of thyroid disease. Regular monitoring of thyroid function is advised for AAV patients, particularly for women, those with coronary artery disease, and those who are positive for anti-Ro/SSA antibodies. Key Points • AAV patients have a higher incidence of thyroid disease. • The potential clinical relevance of AAV patients with thyroid disease was explored. • Regular monitoring of thyroid function is advised for AAV patients. [ABSTRACT FROM AUTHOR]

Granulomatosis of polyangiitis (GPA) is a multisystem necrotizing vasculitis, which affects small- and medium-sized blood vessels and characterized by frequent involvement of the upper and lower respiratory tract and kidneys. Altough anti-neutrophil cytoplasmic antibodies (ANCA) are higly associated with GPA and play an important role in the pathogenesis of this disease, ANCA positivity is not essential for clinical diagnosis. We describe a patient with ANCA-negative granulamatosis of polyangiitis involving cerebellum, having complaints due to sinusitis. [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]

Antineutrophil cytoplasmic antibody-associated (ANCA) vasculitis are a group of autoimmune diseases characterized by inflammation of the microvasculature, leading to life-threatening complications, including kidney disease. These diseases are associated with a high morbidity and mortality rate. Conventional treatment modalities have evolved towards personalized therapies intending to mitigate inflammation and minimize the adverse effects of traditional immunosuppressive agents. Avacopan, a novel C5a receptor inhibitor, represents a promising therapeutic option for vasculitis with renal involvement. This article provides a comprehensive review of the role of complement in the pathogenesis of vasculitis with renal involvement and the role of avacopan for its treatment, taking into account recent updates to both the EULAR and KDIGO guidelines and published experience of avacopan use in real clinical settings. [ABSTRACT FROM AUTHOR]

AbstractBackgroundCase reportConclusionsEosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic, immune-mediated disease that occurs in patients with asthma and eosinophilia. It is characterized by inflammation of small- and medium-caliber blood vessels.This report presents an unusual clinical case of EGPA with positive anti-neutrophil cytoplasmic antibodies who manifested bilateral pleural effusion. The diagnosis was confirmed through laboratory assessments and bronchial biopsies. The patient was treated with methylprednisolone showing improvement in symptoms.Our case appear interesting considering the limited evidence of pleural effusion in patients with EGPA documented in the literature. [ABSTRACT FROM AUTHOR]

The article discusses a rare subtype of idiopathic multicentric Castleman disease known as the TAFRO syndrome, characterized by thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, and organomegaly. The diagnosis of Castleman disease requires careful clinicopathological correlation, and radiographic adrenal abnormalities can serve as a diagnostic clue for TAFRO. Treatment with an interleukin-6 inhibitor is crucial to prevent morbidity and death, with rapid initiation often resulting in excellent outcomes. The case study presented in the article highlights the challenges in diagnosing and treating this rare disease, emphasizing the importance of early recognition and appropriate therapy. [Extracted from the article]

Tumor necrosis factor alpha inhibitors (TNFi) are biological drugs used worldwide to treat various autoimmune disorders. Paradoxically, TNF‐α antagonists can also induce autoimmune diseases being systemic vasculitis, systemic lupus erythematosus, and psoriasis, the most common. We present a 22‐year‐old woman with ulcerative colitis (UC) who was started on adalimumab 40 mg subcutaneously every 2 weeks. After two doses of adalimumab, she developed gangrene of all toes and acute kidney injury requiring hemodialysis. Skin biopsy showed thrombi in the small vessels of the dermis. Renal biopsy disclosed diffuse proliferative glomerulonephritis (GN) and acute tubulointerstitial nephritis. Serologic work‐up showed positive IgG anticardiolipin (ACL) antibodies and low C3 levels. Antinuclear, anti‐dsDNA, anti‐Smith, anti‐SSA, anti‐SSB, anti‐RNP, antineutrophil cytoplasmic antibodies, ACL (IgA and IgM), and anti‐β2‐glycoprotein I (IgG, IgM, and IgA) antibodies were not elevated. Lupus anticoagulant test and cryoglobulins were negative. Adalimumab was discontinued, and she was treated with enoxaparin, intravenous (IV) methylprednisolone pulse, IV cyclophosphamide, and plasmapheresis followed by maintenance therapy with warfarin, prednisone, azathioprine, and hydroxychloroquine. She did not have further thrombotic events, and the acute kidney injury completely resolved. ACL IgG antibodies decreased to normal levels, and repeated tests were negative. After 7 years, anticoagulation and immunosuppressive drugs were discontinued. During a follow‐up of 24 months, she remained in complete clinical remission. This report highlights the occurrence of autoimmune disorders induced by TNFi. Thus, careful monitoring of adverse immune reactions to TNFi is highly recommended. [ABSTRACT FROM AUTHOR]

The article discusses three cases of children diagnosed with juvenile dermatomyositis (JDM) complicated by systemic capillary leak syndrome (SCLS), a condition characterized by capillary leakage leading to anasarca, hemoconcentration, hypoalbuminemia, and hypotension. The cases highlight the severe manifestations of JDM with SCLS, including complications such as shock, acute kidney injury, and acute respiratory distress. Effective management involves aggressive immunosuppression and supportive care, with early recognition and prompt treatment being crucial for successful intervention. The study emphasizes the importance of timely immunosuppression and targeted therapy to reduce morbidity and mortality in such cases. [Extracted from the article]

The article discusses a case of neurosarcoidosis in a 54-year-old female patient with a history of sarcoidosis. The patient experienced visual hallucinations and dizziness, leading to a diagnosis of neurosarcoidosis. Treatment with low-dose methylprednisolone pulse therapy followed by oral methylprednisolone resulted in rapid remission. The case highlights the importance of prompt diagnosis, personalized treatment, and shared decision-making in managing neurosarcoidosis, with a focus on patient-centered care. The successful outcome suggests that dose de-intensification strategies could be beneficial for other neurosarcoidosis patients, potentially influencing future treatment guidelines. [Extracted from the article]

This article from Clinical Case Reports discusses a case of a diabetic patient with focal segmental glomerulosclerosis (FSGS) and infection-related glomerulonephritis (IRGN) leading to rapid renal decline. The patient's complex condition required careful management to balance immunosuppressive treatments for FSGS with infection control strategies for IRGN. The case highlights the importance of multidisciplinary collaboration, timely histopathological assessment, and personalized treatment approaches to prevent irreversible kidney damage in high-risk patients with overlapping pathologies. [Extracted from the article]

A 71-year-old woman presented with a 30-year history of recurrent oral and nasopharyngeal ulcers, facial erythema, vesicles, and scars, along with pancytopenia and elevated ferritin levels. Laboratory tests revealed positive Epstein–Barr virus (EBV) DNA in the blood, leading to a diagnosis of Chronic active EBV disease (CAEBV) of T-cell type. Treatment with oral methylprednisolone and ganciclovir resulted in the resolution of symptoms, highlighting the challenges in diagnosing and treating CAEBV. The study was supported by the Science Foundation of Yunnan Province and the patients provided consent for participation and publication of their case details. [Extracted from the article]

Vasculitis in children represents a diverse group of diseases characterized by inflammation of blood vessels, which can lead to significant morbidity if not promptly recognized and managed. This review explores the epidemiology, pathophysiology, classification, and management of key pediatric vasculitides. Classification based on vessel size aids in diagnosis and treatment. Understanding these conditions” clinical features and therapeutic options is critical for improving pediatric patient outcomes and preventing long-term complications. Continued research is essential for refining treatment strategies and enhancing patient care. [ABSTRACT FROM AUTHOR]

Background: Hashimoto's thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital "R. Dulbecco" in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients. [ABSTRACT FROM AUTHOR]

Objective: Infections are a critical concern for patients with microscopic polyangiitis (MPA). This study aimed to identify the risk factors associated with serious infections (SIs) and infection-related mortality in patients with MPA, as well as the effect of glucocorticoid (GC) dose tapering on these outcomes. Methods: This multicentre, retrospective, and observational study utilised data from a cohort of patients with MPA in Japan [Registry of Vasculitis Patients to Establish REAL World Evidence (REVEAL) cohort]. Patients were categorised based on the occurrence of SIs or infection-related deaths, and various characteristics were compared among the groups. Results: Among 182 patients, 66 (36.2%) experienced 129 SIs and 27 (14.8%) developed infection-related deaths. Advanced age, elevated C-reactive protein (CRP) levels, and higher ratio of the GC dose at 3 months to the initial dose were identified as independent risk factors for SIs. Older age was also associated with infection-related deaths. Furthermore, the cumulative incidence of infection-related deaths was significantly higher in patients with a higher ratio of the GC dose at 24 months to the initial dose. Conclusion: Older age, elevated CRP levels, and slower GC dose tapering predispose patients to SIs and infection-related deaths. Strategies, such as rapid GC dose tapering, are anticipated to mitigate the risk of infections. [ABSTRACT FROM AUTHOR]

Waldenstrom macroglobulinaemia (WM), the predominant subtype of lymphoplasmacytic lymphoma with bone marrow involvement and serum IgM paraprotein, is a haematological condition commonly associated with renal parenchymal involvement. However, antineutrophil cytoplasmic antibody (ANCA)‐negative pauci‐immune crescentic glomerulonephritis (PICGN) in kidney infiltrated by lymphoma is very rare, with only two cases described in chronic lymphocytic leukaemia in English literature so far. We herein report the first patient with WM developing ANCA‐negative PICGN. He was a 76‐year‐old male who presented with elevated serum globulin level and bilateral groin lymph node enlargement, subsequently diagnosed to have WM after pathologic examination of the bone marrow and groin lymph node. One month later, he was found to have acute kidney injury and proteinuria. Renal biopsy confirmed the presence of parenchymal involvement by WM accompanied by PICGN; while ANCA testing was negative. He was treated with pulse methylprednisolone followed by oral prednisolone. In addition, six courses of intravenous rituximab and oral cyclophosphamide were given. There was significant improvement in both his renal and haematological conditions. The clinical course of this case suggested that ANCA‐negative PICGN may represent a paraneoplastic syndrome and a rare manifestation of WM‐associated renal lesion. Early kidney biopsy and prompt treatment may improve the outcome of patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of monoclonal gammopathy of undetermined significance (MGUS) in the population of over 50-year-olds is approximately 3% and increases with age. The association between MG and neuropathy has been of interest for several years, but the causal relationship has not yet been clarified. Methods: For 682 patients who visited the Department of Neurology and requested tests for MG work-up, we retrospectively collected demographic and clinical information, such as age, gender, diagnosis, and neurologic and laboratory test results, from their medical records. Results: Out of a total of 682 patients who were suspected of neuropathy and tested for monoclonal gammopathy (MG), twelve (1.76%) showed MG on their serum protein electrophoresis. The most common form was IgM-κ with five patients, followed by IgG-κ, IgG-λ, and biclonal IgG-λ and IgA-κ. The results of the immunoglobulin quantitation test and free light chain assay showed that involved M-protein values in these patients were increased. Some patients were positive for anti-myelin-associated glycoprotein (MAG) antibody, anti-GD1b IgM antibody, anti-GM1 IgG & IgM antibody, and anti-cardiolipin IgM antibody. Also, some had antinuclear antibody (ANA) or antineutrophil cytoplasmic antibody (ANCA). Conclusions: In the future, it is necessary to investigate the pathogenic relationship between M-protein and autoantibodies in patients with neuropathies. [ABSTRACT FROM AUTHOR]

Objective. This study aimed to compare the 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) classification criteria with the European Medicines Agency (EMA) algorithm for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods. All consecutive, newly diagnosed patients with AAV according to the 2012 Chapel Hill Consensus Conference who visited Keio University Hospital between March 2012 and May 2022 were retrospectively reviewed. Patients were reclassified according to the EMA algorithm and the 2022 ACR/EULAR criteria, and their clinical characteristics were statistically analyzed. Results. A total of 114 patients with AAV were included in the analyses. Using the EMA algorithm as a reference, reclassification of the patients revealed sensitivity and specificity of the 2022 ACR/EULAR criteria of 100% and 96% for eosinophilic granulomatosis with polyangiitis, 40% and 97% for granulomatosis with polyangiitis (GPA), and 90% and 49% for microscopic polyangiitis (MPA), respectively. Approximately half of patients classified as EMA-GPA or EMA-unclassifiable were reclassified as 2022-MPA; these patients were older, were more disposed to be positive for myeloperoxidase (MPO)-ANCA, and had interstitial lung disease (ILD) more frequently than patients with 2022-GPA or non--2022-MPA. Further, some patients positive for MPO-ANCA with biopsy-proven granulomatous inflammation were also reclassified from EMA-GPA to 2022-MPA. Over the mean observation period of 4.0 years, 16 patients died. Overall survival for each classification group differed significantly from the 2022 ACR/EULAR criteria (P = 0.02), but not with the EMA algorithm (P = 0.21). Conclusion. Among the patients classified as EMA-GPA or EMA-unclassifiable, older patients with MPO-ANCA and ILD tended to be reclassified as 2022-MPA. The 2022 ACR/EULAR criteria were more useful in prognostic prediction than the EMA algorithm. [ABSTRACT FROM AUTHOR]

Background: Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings. Objectives: This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM). Results: After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012). Conclusion: Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients. [ABSTRACT FROM AUTHOR]

Here, we report a case of antineutrophil cytoplasmic antibody (ANCA)‐associated central nervous system (CNS) vasculitis that mimicked a brain tumor. The patient presented with progressive right upper arm weakness. Brain magnetic resonance imaging (MRI) revealed large tumor‐like lesions in the left frontal and parietal lobes, with patchy and irregular enhancement with gadolinium and edema. Based on the clinical course and radiological findings, a brain tumor was suspected, and stereotactic brain biopsy was performed. Brain histopathology revealed necrotic tissue and lymphocyte infiltration around small vessels and blood vessel walls. Although the patient's clinical course and pathological findings suggested primary angiitis of CNS (PACNS), double staining for myeloperoxidase (MPO) and CD31 (a neutrophil marker) revealed infiltration of MPO‐positive neutrophils in the blood vessel walls. Therefore, we diagnosed the patient with ANCA‐associated CNS vasculitis. Because CNS vasculitis, including PACNS, presents nonspecific clinical findings and can depict brain tumor‐like MRI findings, CNS vasculitis should be carefully differentiated from brain tumors. Additionally, double staining for MPO and CD31 might be useful for evaluating the pathogenesis of CNS vasculitis. [ABSTRACT FROM AUTHOR]

The article provides an in-depth analysis of the immune and non-immune mediators involved in the fibrosis pathogenesis of salivary glands in Sjögren's syndrome. It explores the impact of chronic inflammation, immune cell interactions, viral infections, and molecular mechanisms on the development of fibrosis. The document also discusses therapeutic strategies targeting immune cells and fibroblasts to alleviate fibrosis in Sjögren's syndrome, emphasizing the need for further research to understand the complex pathogenesis and develop effective treatments. Additionally, it delves into the correlation of T follicular helper cells with immunopathology, therapeutic options for systemic sclerosis, and the unique expansion of IL-21+ Tfh and Tph cells in Sjögren's syndrome with ectopic germinal centers and malt lymphoma. [Extracted from the article]

Introduction: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection, the causative agent of coronavirus disease 2019 (COVID-19), causes post-acute infection syndrome in a surprisingly large number of cases worldwide. This condition, also known as long COVID or post-acute sequelae of COVID-19, is characterized by extremely complex symptoms and pathology. There is a growing consensus that this condition is a consequence of virusinduced immune activation and the inflammatory cascade, with its prolonged duration caused by a persistent virus reservoir. Methods: In this cross-sectional study, we analyzed the SARS-CoV-2-specific T cell response against the spike, nucleocapsid, and membrane proteins, as well as the levels of spike-specific IgG antibodies in 51 healthcare workers, categorized into long COVID or convalescent control groups based on the presence or absence of post-acute symptoms. Additionally, we compared the levels of autoantibodies previously identified during acute or critical COVID-19, including anti-dsDNA, anti-cardiolipin, anti-b2-glycoprotein I, anti-neutrophil cytoplasmic antibodies, and anti-thyroid peroxidase (anti-TPO). Furthermore, we analyzed the antibody levels targeting six nuclear antigens within the ENA-6 S panel, as positivity for certain anti-nuclear antibodies has recently been shown to associate not only with acute COVID-19 but also with long COVID. Finally, we examined the frequency of diabetes in both groups. Our investigations were conducted at an average of 18.2 months (convalescent control group) and 23.1 months (long COVID group) after confirmed acute COVID-19 infection, and an average of 21 months after booster vaccination. Results: Our results showed significant differences between the two groups regarding the occurrence of acute infection relative to administering the individual vaccine doses, the frequency of acute symptoms, and the T cell response against all structural SARS-CoV-2 proteins. A statistical association was observed between the incidence of long COVID symptoms and highly elevated anti-TPO antibodies based on Pearson's chi-squared test. Although patients with long COVID showed moderately elevated anti-SARS-CoV-2 spike IgG serum antibody levels compared to control participants, and further differences were found regarding the positivity for anti-nuclear antibodies, anti-dsDNA, and HbA1c levels between the two groups, these differences were not statistically significant. Disscussion: This study highlights the need for close monitoring of long COVID development in patients with elevated anti-TPO titers, which can be indicated by strongly elevated SARS-CoV-2-specific T cell response and moderately raised anti-spike IgG levels even long after the acute infection. However, our results do not exclude the possibility of new-onset thyroid autoimmunity after COVID-19, and further investigations are required to clarify the etiological link between highly elevated anti-TPO titers and long COVID. [ABSTRACT FROM AUTHOR]

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]

The article discusses a case study of a 1-year-old girl with diffuse alveolar hemorrhage (DAH) as the initial presentation of hypomorphic RAG1 deficiency, a combined immunodeficiency disorder. The patient experienced severe respiratory symptoms, anemia, and abnormal immune cell counts, leading to a diagnosis of leaky severe combined immunodeficiency. Treatment with corticosteroids and immunoglobulins showed improvement, but the patient later died due to acute respiratory failure. The study highlights the importance of considering RAG1 deficiency in DAH cases and expanding autoantibody testing to anti-cytokine antibodies for diagnosis. [Extracted from the article]

The article discusses a case of erythema nodosum (EN) induced by a tumor necrosis factor‐alpha (TNF‐α) inhibitor in a 60‐year‐old female patient with peripheral spondyloarthritis. The patient developed painful nodules on her legs after treatment with adalimumab and later etanercept. The article provides a comprehensive literature review of similar cases and highlights the importance of considering EN as a potential side effect of anti‐TNF therapy. The authors emphasize the need for a thorough diagnostic workup to rule out other causes of EN and suggest collaborative management with a dermatologist while maintaining anti‐TNF therapy if it effectively controls the underlying autoimmune condition. [Extracted from the article]

Objectives: We applied the 2022 American College of Rheumatology/ European Alliance of Association for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients histologically diagnosed with lupus nephritis (LN) to investigate the overall rate of and initial contributing factors to the reclassification of overlap syndrome of LN with AAV (OS-LN-AAV). Methods: We retrospectively reviewed the medical records of 1292 patients with systemic lupus erythematosus (SLE) and included 164 patients with LN in this study. Patient demographics, SLE manifestations, LN classes, and laboratory data, including ANCA levels, were recorded. All-cause mortality and end-stage kidney disease (ESKD) were evaluated as poor outcomes. Results: The median age of the 164 patients was 37.0 years, and 12.2% were men. The overall reclassification rate was 37.8%, of which 34.1% and 3.7% of the patients were reclassified as having OS-LN-microscopic polyangiitis and OS-LN-granulomatosis with polyangiitis (GPA), respectively, but none as having eosinophilic GPA. ANCA positivity and AAV-suggesting lung lesions were major contributors to OS-LN-AAV reclassification. When patients were compared based on OS-LN AAV reclassification, ANCA positivity and myeloperoxidase-ANCA (or P-ANCA) positivity favoured for OS-LN-AAV reclassification, whereas oral ulcers did not. However, OS-LN-AAV reclassification did not affect all-cause mortality or ESKD. Conclusions: This is the first study demonstrating a 37.8% reclassification rate in patients histologically diagnosed with LN using the 2022 ACR/EULAR criteria for AAV. Furthermore, it was also the first to reveal ANCA positivity and AAV-suggesting lung lesions as major contributors to OS-LN-AAV reclassification. [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]

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]

Introduction: Nephrotic syndrome (NS) is a common childhood glomerular disease. The most common presentation in paediatric population is the idiopathic syndrome (INS). Treatment with levamisole is effective in frequent re- lapsing and corticosteroid-dependent NS. Studies have reported mild and rarely severe side effects, which subside after treatment withdrawal. Results: We describe two clinical cases of frequently relapsing INS treated with levamisole that presented with cutaneous vasculitis with positive anti-neutrophil cytoplasmic antibodies. Both cases had skin lesions that disappeared after withdrawal of the drug, avoiding the use of other treatments with corticosteroids, immunomodulators and even amputations due to skin necrosis. Conclusions: It is important to know the possible complications of levamisole treatment in paediatric patients with INS to proceed with drug withdrawal for resolution. [ABSTRACT FROM AUTHOR]

Purpose: To report an uncommon, isolated presentation of bilateral choroidal detachments in a patient diagnosed with P-ANCA-associated vasculitis and to highlight the importance of an inflammatory work-up in such cases. Methods: Case report. Results: A 70-year-old male with a past medical history of autoimmune hepatitis presented with a sudden decrease in vision in both eyes. Over the course of the previous decade, he had experienced recurrent attacks of episcleritis, which were successfully managed with topical corticosteroid eye drops. The patient was diagnosed with bilateral detachments without accompanying scleritis or intraocular inflammation. Inflammatory markers revealed high P-ANCA and anti-MPO levels, confirming the diagnosis of P-ANCA-associated vasculitis. Treatment with systemic rituximab and corticosteroids led to the resolution of the choroidal detachment in both eyes. A 40-month follow-up confirmed the sustained resolution of the detachments. Conclusion: Choroidal detachment without other extraocular/intraocular inflammation can be associated with P-ANCA-associated vasculitis, a previously under-reported link. It is important to consider an inflammatory work-up for patients presenting with choroidal detachment to rule out conditions like P-ANCA-associated vasculitis. [ABSTRACT FROM AUTHOR]

This article discusses a study that examined the frequency of positive antineutrophil cytoplasmic antibody (ANCA) tests during the COVID-19 pandemic compared to before the pandemic. The study found that both PR3-ANCA and MPO-ANCA tests were more commonly ordered during the pandemic. Positive results for PR3-ANCA were more frequently detected during the pandemic, while positive results for MPO-ANCA were more commonly detected before the pandemic. The study suggests a potential link between COVID-19 and the development of autoimmune diseases, but further research is needed to understand the underlying mechanisms. The study also emphasizes the importance of educating physicians about ANCA and autoimmune vasculitis. [Extracted from the article]

Immunoglobulin glycosylation is a pivotal mechanism that drives the diversification of antibody functions. The composition of the IgG glycome is influenced by environmental factors, genetic traits and inflammatory contexts. Differential IgG glycosylation has been shown to intricately modulate IgG effector functions and has a role in the initiation and progression of various diseases. Analysis of IgG glycosylation is therefore a promising tool for predicting disease severity. Several autoimmune and alloimmune disorders, including critical and potentially life-threatening conditions such as systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and antibody-mediated kidney graft rejection, are driven by immunoglobulin. In certain IgG-driven kidney diseases, including primary membranous nephropathy, IgA nephropathy and lupus nephritis, particular glycome characteristics can enhance in situ complement activation and the recruitment of innate immune cells, resulting in more severe kidney damage. Hypofucosylation, hypogalactosylation and hyposialylation are the most common IgG glycosylation traits identified in these diseases. Modulating IgG glycosylation could therefore be a promising therapeutic strategy for regulating the immune mechanisms that underlie IgG-driven kidney diseases and potentially reduce the burden of immunosuppressive drugs in affected patients. Here, the authors review the impact of IgG glycosylation in kidney diseases, particularly autoimmune diseases and antibody-mediated rejection. They also discuss the signalling pathways that govern antibody glycosylation, the impact of glycosylation on antibody functions and implications for therapy. Key points: Aberrant glycosylation of IgG is influenced by antibody subclass and antigen specificity and is established during B cell differentiation and maturation within germinal centres. Hypogalactosylation of the fragment crystallizable (Fc) of anti-PLA2R1 is a key feature of primary membranous nephropathy. Hypogalactosylation and hyposialylation of the Fc portion of anti-neutrophil cytoplasmic antibodies and total IgG in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are associated with more severe disease and disease relapse. Among patients with systemic lupus erythematosus, those with lupus nephritis have reduced levels of galactosylation of the Fc portion of total IgG. In patients with IgA nephropathy, hypogalactosylated IgA1 triggers the generation of anti-hypogalactosylated IgA1 autoantibodies, leading to the formation of immune complexes. Aberrant hyposialylation and hypofucosylation of donor-specific antibodies are associated with antibody-mediated rejection of kidney grafts. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and glomerulonephritis is uncommon in children. We sought to characterize the histological and clinical features of the disease and report on risk factors for adverse outcomes in a pediatric cohort. Methods: Retrospective single-center cohort of all pediatric (< 20 years) patients diagnosed with ANCA-associated glomerulonephritis (AAGN) by kidney biopsy between 2002 and 2022 at Johns Hopkins University. Histological and clinical features were extracted from the medical record. Clinical, laboratory, and histological findings were analyzed to determine the association with kidney failure (KF) and/or death. Results: A total of 17 patients were identified (GPA n = 7, MPA = 10) with a median age of 15 years (IQR 12–17) at presentation, a slight female predominance (59%), with seven patients reaching the composite outcome of death (n = 1) or kidney failure (n = 6). There was no difference in presenting clinical symptoms or extra-renal manifestations between the two groups. Univariable Cox regression identified several factors associated with an increased hazard of endpoint including the degree of global or segmental sclerosis, interstitial fibrosis and tubular atrophy (IFTA), C3 and C1q staining, presence of subendothelial deposits, and proteinuria. Multivariable regression was not performed due to the small sample size. We saw a trend towards increased utilization of plasma exchange and a decrease in cyclophosphamide utilization in the more recent era. There was no association between treatment modality and outcome. Conclusions: Pediatric AAGN is a rare disease associated with significant morbidity. We identified glomerulosclerosis and IFTA on histology, and proteinuria on initial presentation as risk factors for KF/death. [ABSTRACT FROM AUTHOR]

Children with anti-neutrophil cytoplasmic antibody-associated vasculitis benefit immensely from avacopan as it reduces the requirement for steroids. However, descriptions of adverse drug reactions in children are lacking, and the dosage and follow-up intervals are unclear. A 10-year-old boy with initial granulomatosis and polyangiitis presented with diffuse pulmonary hemorrhage. Rituximab and 30 mg avacopan were administered twice daily as induction therapy following methylprednisolone pulse therapy. However, sudden liver function test abnormalities were observed on day 31 of avacopan treatment, despite liver enzyme levels being within the normal range 5 days earlier. A drug-induced lymphocyte stimulation and various infectious disease tests yielded negative results. Discontinuation of rituximab and avacopan resulted in improved liver function; no change in the Birmingham Vasculitis Activity Score during liver function test abnormalities was observed. Avacopan-associated abnormalities in liver function tests suggest that drug-induced liver injury may occur rapidly in children, and appropriate dosing strategies should be reconsidered. [ABSTRACT FROM AUTHOR]

Background and Objectives: Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein primarily produced by cells in the central nervous system (CNS) and other major organs such as the kidneys. This study investigated whether serum GFAP could be used to estimate cross-sectional vasculitis activity presented via the Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 74 patients with AAV. Clinical and laboratory data at diagnosis including BVAS and C-reactive protein (CRP) were reviewed. During follow-up, all-cause mortality and end-stage kidney disease (ESKD) were considered poor outcomes. Serum GFAP was measured from sera collected and stored at diagnosis. Results: The median age of the 74 patients was 63.5 years. Serum GFAP was inversely correlated with the cross-sectional BVAS (r = −0.373) and CRP (r = −0.320). It was also significantly correlated with general (r = −0.237) and renal (r = −0.335) manifestations among BVAS systemic items, and furthermore, among minor items of renal manifestation, correlating with sum scores for proteinuria (r = −0.409) and haematuria (r = −0.305). Additionally, compared with patients with serum GFAP > 194.9 pg/mL, those with serum GFAP ≤ 194.9 pg/mL showed a higher risk for progression to ESKD (relative risk 3.150) and a significantly lower cumulative ESKD-free survival rate. Conclusions: This study demonstrated the clinical potential of serum GFAP at diagnosis for predicting not only cross-sectional vasculitis activity through the anticipation of the extent of renal involvement but also future progression to ESKD in patients with AAV. [ABSTRACT FROM AUTHOR]

Objective: Avacopan, an activated complement factor 5 receptor antagonist, has been approved as adjunct therapy for severe active antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Current evidence supports the management of AAV presenting with diffuse alveolar hemorrhage (DAH) by administering glucocorticoids combined with either rituximab or cyclophosphamide in addition to supportive care. The role of avacopan in patients with DAH as a primary severe disease manifestation of AAV has not been well established. Furthermore, concerns remain regarding timely access to avacopan, the best glucocorticoid tapering regimen, and long‐term efficacy and safety of the drug. We sought to identify clinical features and outcomes of patients presenting with DAH secondary to AAV who received avacopan in addition to glucocorticoids and rituximab or cyclophosphamide. Methods: We performed a retrospective cohort study of all consecutive patients presenting with DAH as part of active severe granulomatosis with polyangiitis or microscopic polyangiitis. Demographic and clinical characteristics were collected at presentation and follow‐up. Results: Fifteen patients met inclusion criteria and were observed for a median time of 17 weeks (interquartile range [IQR] 6–37 weeks) after initiation of avacopan. Patients were predominantly female and White, had never smoked, and were a median age of 66 years (IQR 52–72 years) at diagnosis. The majority had newly diagnosed severe AAV with renal involvement. Three patients progressed to respiratory failure. The timing of avacopan introduction and patterns of glucocorticoid tapers varied widely in this cohort. Two serious adverse events related to infection were observed, including one opportunistic infection leading to the patient's death, although neither was directly attributed to avacopan administration. Conclusion: We describe the clinical course of patients who presented with the severe AAV disease manifestation of DAH and received avacopan as adjunct therapy. Most patients achieved remission during follow‐up, and adverse events, including infection, were observed. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that cardiovascular disease and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are interconnected. This investigation aims to examine the epidemiology, potential risk, and cardiovascular events among AAV sufferers to shed light on the intricate relationship between these seemingly unrelated conditions. A systematic review following PRISMA criteria encompassed 18 relevant studies with a pooled sample size of 21,291 ANCA-associated vasculitis patients. Studies were retrieved from PubMed, Embase, and Cochrane Library. Inclusion criteria focused on longitudinal studies reporting cardiovascular events in AAV patients. Data extraction and synthesis were performed, focusing on prevalence, types of cardiovascular events, comparison with control groups, and identification of risk factors and independent predictors. The study found that patients with ANCA-associated vasculitis had a mean age of 57.5 years, with 47% being male. The mean follow-up duration was 4.77 years. Overall, 1350 cardiovascular events were reported across the studies, yielding a pooled prevalence of 6.3%. Major adverse cardiovascular events, ischemic heart disease, stroke, venous thromboembolism, and acute coronary syndromes were the specific events. Comparison with control groups demonstrated a higher cardiovascular risk in AAV patients. Age, systolic blood pressure, estimated glomerular filtration rate, and the Birmingham Vasculitis Activity Score were independent predictors. In conclusion, ANCA-associated vasculitis patients have elevated cardiovascular risk and a variety of manifestations. AAV-specific variables,such as inflammation and disease activity, and conventional risk factors, play a role in cardiovascular complications. The study challenges conventional assessment timelines by highlighting the importance of early and proactive cardiovascular risk management.

Objective: Pulmonary infection is one of the leading causes of death in patients with ANCA-associated vasculitis (AAV). It is sometimes difficult to differentiate pulmonary infection from pulmonary involvement of vasculitis in AAV patients. Fiberoptic bronchoscopy and bronchoalveolar lavage fluid (BALF) assays are useful diagnostic methods. In addition to conventional microbiological tests (CMTs), metagenomic next-generation sequencing (mNGS) facilitates rapid and sensitive detection of various pathogens. The current study aimed to evaluate the advantages of additional BALF mNGS in the management of pulmonary infection in AAV patients. Methods: 27 patients with active AAV and suspected pulmonary infection whose BALF samples were tested by mNGS and CMTs and 17 active AAV patients whose BALF were tested by CMTs alone were retrospectively recruited. The results of microbiological tests, and adjustments of treatment following BALF mNGS, were described. The durations of antimicrobial treatment and in-hospital mortality in patients were compared. Results: Among the 27 patients whose BALF samples were tested by mNGS, 25.9% of patients did not have evidence of pathogenic microorganism in their BALF samples, 55.6% had polymicrobial infections, including bacteria, fungi and viruses. Of these 27 patients, 40.7% did not have evidence of pathogenic microorganism in their BALF or serum samples according to CMTs. Patients in the BALF mNGS/CMT group received a significantly shorter duration of antibacterial and total antimicrobial treatment than patients in the CMT alone group (17.3 ± 14.7 vs. 27.9 ± 19.0 days, P = 0.044; 18.9 ± 15.0 vs. 29.5 ± 17.7 days, P = 0.040, respectively). Fewer patients in the BALF mNGS/CMT group died than in the CMT alone group (4/27 vs. 7/17, P = 0.049). Conclusion: Compared with CMT alone, additional mNGS tests may shorten the duration of antimicrobial treatment and possibly decrease death from severe infection by providing precise and quick diagnosis of infection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (GN). To date, treatment of most patients with ANCA-GN relies on non-specific immunosuppressive agents, which may have serious adverse effects and be only partially effective. Here, using spatial and single-cell transcriptome analysis, we characterize inflammatory niches in kidney samples from 34 patients with ANCA-GN and identify proinflammatory, cytokine-producing CD4+ and CD8+ T cells as a pathogenic signature. We then utilize these transcriptomic profiles for digital pharmacology and identify ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, as the strongest therapeutic drug to use. Moreover, four patients with relapsing ANCA-GN are treated with ustekinumab in combination with low-dose cyclophosphamide and steroids, with ustekinumab given subcutaneously (90 mg) at weeks 0, 4, 12, and 24. Patients are followed up for 26 weeks to find this treatment well-tolerated and inducing clinical responses, including improved kidney function and Birmingham Vasculitis Activity Score, in all ANCA-GN patients. Our findings thus suggest that targeting of pathogenic T cells in ANCA-GN patients with ustekinumab might represent a potential approach and warrants further investigation in clinical trials. Antineutrophil cytoplasmic antibody (ANCA) is currently treated with broad-spectrum immune suppressive drugs. Here the authors decipher inflammatory niches in the kidney of patients with ANCA-GN by combining spatial and single-cell transcriptomics to identify ustekinumab as a promising treatment option and successfully treat four ANCA-GN patients. [ABSTRACT FROM AUTHOR]

Kidney complications can occur due to infective endocarditis, one of which is glomerulonephritis. Most often, an immune complex or complement‐mediated glomerulonephritis is seen on kidney biopsy. In a minor subset of cases, pauci‐immune glomerulonephritis may be present. Most often, such patients will demonstrate the presence of antineutrophil cytoplasmic antibodies (ANCA) on serologic testing. A growing number of cases of ANCA‐associated glomerulonephritis due to Bartonella endocarditis have been reported. This type of endocarditis can present diagnostic difficulties given that these patients are often culture negative. Herein, we report a challenging case of ANCA‐negative pauci‐immune glomerulonephritis showing florid crescents on biopsy that was associated with Bartonella endocarditis. [ABSTRACT FROM AUTHOR]

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]

Objective: Antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is divided into granulomatosis with polyangiitis (GPA), microscopic polyangiitis, and eosinophilic GPA. It is one of the most severe and potentially fatal autoimmune inflammatory conditions. The etiology and pathology of AAV are complex and poorly understood. Since the onset of the Coronavirus Disease 2019 (COVID‐19) pandemic, numerous reports have documented GPA cases following COVID‐19, suggesting a potential link between COVID‐19 and the development of GPA. This case report discusses a 16‐year‐old East Asian boy who developed GPA with diffuse alveolar hemorrhage after contracting COVID‐19. Additionally, a literature review was conducted to gain a deeper understanding of this disorder. Methods: The study involved a retrospective analysis of the data of a case of GPA post‐COVID‐19 infection, aiming to summarize the clinical characteristics of GPA post‐COVID‐19 infection through a search of databases (PubMed, Wanfang Data, and CNKI), supplemented by standard searches in Google Scholar, Cochrane, Scopus, and LitCovid, and to conduct a comprehensive analysis of the literature. Results: A total of 12 cases were identified and, when combined with the present case, yielded 13 cases of GPA post‐COVID‐19 infection, comprising 5 males and 8 females with an average age of (40.6 ± 19.5) years. The interval between COVID‐19 infection and the diagnosis of GPA varied from 1 day to 3 months across all cases. Mortality was reported at 7.7% (1/13). The most common clinical manifestations included cough (69.2%) and dyspnea (46.1%). Computed tomography scans revealed ground‐glass opacities and multifocal pulmonary nodules. In all cases, positive findings for c‐ANCA and protease 3‐antibody were observed. Renal involvement was observed in more than half of the patients. [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]

This article discusses a study on the effectiveness of combination maintenance therapy with mepolizumab (MEP) and azathioprine (AZA) for eosinophilic granulomatosis with polyangiitis (EGPA), a disease that affects various organs in the body. The study found that adding MEP to the treatment regimen resulted in higher remission rates and lower doses of glucocorticoids (GCs). Some patients were even able to discontinue GCs altogether. The findings suggest that MEP and AZA may be an effective combination therapy for severe EGPA, but further research is needed to fully understand its impact. The study was supported by a research grant and the authors have no conflicts of interest. [Extracted from the article]

This article discusses a case of a 73-year-old Chinese woman who developed rapidly progressive glomerulonephritis (RPGN) and IgA nephropathy (IgAN) after using the medication golimumab. The patient had a history of seronegative rheumatoid arthritis and was initially treated with prednisolone and hydroxychloroquine. After a flare-up, she was treated with corticosteroids and disease-modifying antirheumatic drugs (DMARDs), but developed rashes to sulfasalazine and methotrexate. She was then started on golimumab, a TNF-alpha inhibitor, and remained in clinical remission for 2 years until her current presentation with fever and gross hematuria. The patient's medical history did not include diabetes or hypertension. The article explores the potential mechanisms by which TNF-alpha inhibitors like golimumab can trigger immune-mediated glomerular diseases and discusses the treatment strategy used in this case. The patient showed improvement after discontinuing golimumab and receiving corticosteroid and mycophenolate mofetil treatment. This is the first reported case of crescentic IgAN associated with golimumab use. [Extracted from the article]

Objective Von Willebrand factor (VWF) antigen plays a role in vascular inflammation and thrombosis, both of which are important in the pathogenesis of ANCA-associated vasculitis (AAV). Previous work found that VWF correlates with disease activity in childhood-onset primary CNS vasculitis. We sought to determine the relationship between VWF and disease activity over time in children with AAV. Methods AAV patients with more than one VWF level measured were included in this retrospective study, and the relationships between active vasculitis, VWF and other disease measures were analysed. Generalized estimating equations analysis was used to account for repeated VWF measurements within a patient. Repeated measures correlation was used to determine associations of paired laboratory observations. Diagnostic performance was evaluated using receiver operating curve analysis. Results A total of 732 total VWF measurements were collected in 33 AAV patients. VWF antigen levels were higher during active disease [median 2.03 IU/ml, interquartile range (IQR) 1.35, 2.55] compared with inactive disease (median 1.18 IU/ml, IQR 0.94, 1.53). VWF antigen was the only variable that was significantly associated with active disease (odds ratio 3.01, P  < 0.001, 95% CI 2.3, 3.93). The effect of VWF did not show a substantial difference between the disease subtypes. There was a moderate positive correlation between VWF antigen and disease activity, with an acceptable sensitivity and specificity rates. Conclusion Increased VWF antigen levels correlate with active vasculitis in this paediatric-onset AAV cohort and may be used as an additional biomarker in childhood AAV. [ABSTRACT FROM AUTHOR]

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of rare diseases with a chronic and relapsing course. Recent treatment guidelines offer many therapeutic options depending mainly on the type of diagnosis and disease manifestations. Areas that remain under discussion include whether all patients diagnosed with AAV belong to a homogeneous group with a similar prognosis at baseline or if the type and duration of remission-inducing treatment should depend on factors other than just diagnosis and disease severity. The aim of this review is to present the recent literature on the tools available to use while evaluating the risk of relapse in patients upon presentation as well as potential biomarkers of proceeding flare in patients upon remission. [ABSTRACT FROM AUTHOR]

Background: Pauci‐immune glomerulonephritis (GN) due to antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is a common cause of crescentic GN. Despite advances in treatment, rates of mortality and progression to end‐stage kidney disease remain high. Renal involvement is diagnosed by histological examination of kidney tissue. Serum ANCAs play a significant role in AAV; however, the value of serum ANCA quantification to predict renal involvement is not well‐established. Aim: We aimed to evaluate the diagnostic accuracy of serum ANCA titres in diagnosing AAV with renal involvement. Methods: We conducted a retrospective study of consecutive native kidney biopsies reported at our centre from 2016 to 2021. We included all adults who had both a kidney biopsy and ANCA serology. ANCA serology was tested using indirect immunofluorescence with reporting of titres. Antibodies to proteinase 3 and myeloperoxidase were measured using a chemiluminescent immunoassay. Results: Eight hundred and forty‐eight native kidney biopsies were reported during the study period. Five hundred and seven cases were included. The biopsy prevalence of pauci‐immune GN in paired samples was 41/507 (8.1%). Most of the cohort had haematuria (66.6%), proteinuria (93.4%) and/or acute kidney injury (65.0%). A positive ANCA at any titre demonstrated a sensitivity of 97.6% and a specificity of 71.2% for a diagnosis of pauci‐immune GN. The area under the curve for the receiver operator characteristic was 0.93 (95% confidence interval [CI]: 0.89–0.97). A cutoff ANCA titre of 1:160 provided the optimum balance between a sensitivity of 75.6% (95% CI: 59.7%–87.6%) and a specificity of 94.0% (95% CI: 91.6%–96.0%). Conclusions: ANCA titres are highly predictive of pauci‐immune GN in the appropriate context. While serum ANCA quantitation may not replace renal biopsy, reporting will assist in the decision to start treatment early for patients with organ or life‐threatening disease. [ABSTRACT FROM AUTHOR]