Myeloperoxidase-antineutrophil Cytoplasmic Antibody Research Articles

Severe Pulmonary Embolism, Thrombosis of Lower Extremity, Unexpected Mild Renal Disorder in MPO-ANCAAssociated Vasculitis: A Case Report

Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis is an autoimmune disease usually with severe multiple dysfunction syndrome, especially prominent acute renal failure. A 65-year-old woman was admitted with progressive dyspnoea for six months and fever, sputum with blood, pain of the lower extremities and intermittent claudication for two days, indicating multiple organ involvement (respiratory system, blood vessels). The renal involvement was relatively mild, presenting with microscopic haematuria. The chest computed tomography demonstrated multiple pulmonary embolisms. Ultrasound and computed tomography angiography for the lower extremity vessels showed venous and arterial thrombosis. Exclusion of other diseases that can cause multiple organ damage and thrombosis, the positive perinuclear ANCA and MPO-ANCA strongly support the diagnosis of MPO-ANAC-associated vasculitis. The patient's physical condition has been greatly improved by treatment with corticosteroids and anticoagulation.

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

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

A Potential Alternative Therapy for MPO-ANCA Vasculitis with IVIG in a Patient with COVID-19

The presenting patient is a 76-year-old woman with a history of duodenal ulcers status post perforation, subsequent repair via ex-laparotomy, multiple gastrointestinal bleeds, chronic anemia, and chronic kidney disease stage IV. She was admitted for COVID-19 in the setting of acute kidney injury and was found to have myeloperoxidase-anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) vasculitis.

47-Year-Old Woman With Bilateral Flank Pain

47-Year-Old Woman With Bilateral Flank Pain

Optic neuropathy secondary to granulomatosis with polyangiitis in a patient with Graves\u2019 disease: a case report

BackgroundDysthyroid optic neuropathy is the most commonly suspected diagnosis of optic neuropathy in Graves’ patients; however, other causes need to be ruled out. We present a unique case of optic neuropathy secondary to hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be antithyroid drug related.Case presentationA 79-year-old Japanese male presented with acute visual loss in the left eye. He had a 24-year history of Graves’ disease and was taking methimazole. Best-corrected visual acuity was 0.8 in the right eye and light perception in the left eye, and relative afferent pupillary defect in the left eye was seen. Ocular movement was normal, and there were no findings explaining visual loss in intermediate optic media and fundus in the left eye. Contrast-enhanced magnetic resonance imaging demonstrated thickened dura mater. Tests for myeloperoxidase-antineutrophil cytoplasmic antibody, proteinuria, and hematuria were positive; pulmonary nodule lesions and a blood clot in the left lower leg were also found. After excluding the presence of diseases that could lead to hypertrophic pachymeningitis, we diagnosed optic neuropathy due to hypertrophic pachymeningitis with granulomatosis with polyangiitis—a subtype of antineutrophil cytoplasmic antibody-associated vasculitis. Since he had history of using methimazole, antineutrophil cytoplasmic antibody-associated vasculitis was considered as drug related. We started high-dosage steroid pulse therapy followed by 1 mg/kg body weight daily of oral prednisolone, and subsequently tapered. Methimazole was stopped. Best-corrected visual acuity recovered to 0.9, 2 weeks after starting treatment. Though myeloperoxidase-antineutrophil cytoplasmic antibody remained negative, the symptom relapsed 6 months after treatment initiation. We gave a second high-dose steroid pulse therapy followed by prednisolone tapered together with methotrexate. Remission remained, and using 4 mg/week methotrexate without prednisolone, myeloperoxidase-antineutrophil cytoplasmic antibody was kept within the normal limit until now, 4 years after onset.ConclusionWe present a case of optic neuropathy with hypertrophic pachymeningitis related to antineutrophil cytoplasmic antibody-associated vasculitis, which was suspected to be drug related. The patient had good visual recovery after quitting the drug and receiving immunosuppressive therapy with systemic steroids. Hypertrophic pachymeningitis with antineutrophil cytoplasmic antibody-associated vasculitis related to antithyroid drugs should be considered as a differential diagnosis for optic neuropathy in Graves’ patients in whom optic nerve compression is not obvious.

Prevalence of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Spatial Association With Quarries in a Region of Northeastern France: A Capture-Recapture and Geospatial Analysis.

Silica is an environmental substance strongly linked with autoimmunity. The aim of this study was to assess the prevalence of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and renal limited vasculitis, in a northeastern region of France and to evaluate whether there was a geospatial association between the localization of quarries in the region and the prevalence of these AAVs. Potential AAV patients were identified using 3 sources: hospital records, immunology laboratories, and the French National Health Insurance System. Patients who resided in the Alsace region of France as of January 1, 2016 and who fulfilled the American College of Rheumatology criteria for GPA or the 2012 Chapel Hill Consensus Conference definitions for GPA or MPA were included. Incomplete case ascertainment was corrected using a capture-recapture analysis. The spatial association between the number of cases and the presence of quarries in each administrative entity was assessed using regression analyses weighted for geographic region. Among 910 potential AAV patients, we identified 185 patients fulfilling inclusion criteria: 120 patients with GPA, 35 patients with MPA, and 30 patients with renal limited vasculitis. The number of cases missed by any source as estimated by capture-recapture analysis was 6.4 (95% confidence interval [95% CI] 3.6-11.5). Accordingly, the estimated prevalence in Alsace in 2016 was 65.5 GPA cases per million inhabitants (95% CI 47.3-93.0), 19.1 MPA cases per million inhabitants (95% CI 11.3-34.3), and 16.8 renal limited vasculitis cases per million inhabitants (95% CI 8.7-35.2). The risk of AAV was significantly increased in communities with quarries (odds ratio 2.51 [95% CI 1.66-3.80]), and geographic-weighted regression analyses revealed a significant spatial association between the proximity to quarries and the number of GPA cases (P = 0.039). In analyses stratifying the AAV patients by ANCA serotype, a significant association between the presence of quarries and positivity for both proteinase 3 ANCAs (P = 0.04) and myeloperoxidase ANCAs (P = 0.03) was observed. In a region with a high density of quarries, the spatial association between the presence of and proximity to quarries and the prevalence of AAVs supports the idea that silica may have a role as a specific environmental factor in this disease.

A RARE RADIOGRAPHIC MANIFESTATION OF A CHRONIC COUGH

TOPIC: Imaging TYPE: Medical Student/Resident Case Reports INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is characterized by small vessel necrotizing vasculitis. AAV, including microscopic polyangiitis (MPA), is uncommonly association with interstitial lung disease (ILD). We present a pulmonary presentation of MPA with unique radiographic manifestations. CASE PRESENTATION: A 68-year-old woman with history of hypertension, hyperlipidemia, chronic lymphocytic thyroiditis and obesity presented with 8 weeks of dry hacking cough, associated with dyspnea on exertion and a 20lb weight loss. She was without sinusitis, visual changes, hemoptysis, abdominal symptoms, paresthesia, skin changes, or arthritis. Her initial prescriptions of loratadine and 10-days of doxycycline, then 10-days of prednisone had no effect. She was transitioned off Lisinopril to only mild improvement in her cough.The ILD CHEST questionnaire was completed without obvious toxic insult noted [1]. Her initial workup revealed mild leukocytosis (13), urinalysis with 1+ occult blood, normal Creatine Kinase, Aldolase, Thyroid studies, Liver function tests, electrolytes, and creatinine. Infectious workup was negative for HIV and COVID-19. High-resolution chest imaging demonstrated bilateral central bronchial wall thickening and inflammation and no pleural reticulation, honeycombing, nor adenopathy.Bronchoscopy with transbronchial and endobronchial biopsies revealed intra-alveolar hemorrhage and hemosiderin-laden macrophages but without definitive vasculitis. Infectious workup was unremarkable. Antinuclear and glomerular basement membrane antibody testing was negative. Serologic testing was notable for perinuclear anti-neutrophil cytoplasmic antibody titer of 1:640 (<1:20) and positive myeloperoxidase antibodies. Nephrology evaluation showed evidence of glomerulonephritis with dysmorphic hematuria and proteinuria, and Rheumatological evaluation revealed elevated sedimentation rate 120 mm/H (<20) and C-reactive protein 61mg/L (<10). DISCUSSION: Given concern for pulmonary and renal end-organ involvement, prednisone 60mg daily with Bactrim for Pneumocystis Jirovecii prophylaxis was started. Her cough markedly improved. Her case was discussed internally at our Multidisciplinary ILD board and she was transitioned to Rituximab induction for MPA/AAV treatment. Her cough has resolved with no functional dyspnea while on therapy. CONCLUSIONS: ILD is an uncommon associated finding in MPA. When present, more common radiographic manifestations include ground glace opacities, reticulations, interlobular septal thickening and even honeycombing (2). Our case was notable for radiographic central bronchial wall thickening and inflammation alone, a rare manifestation [2,3]. When present, bronchial wall thickening is typically seen in association with usual interstitial pneumonia or diffuse alveolar hemorrhage [2]. The latter of which was identified during our patient's bronchoscopy. REFERENCE #1: www.chestnet.org. [last accessed 2021 April 20]. REFERENCE #2: Suzuki A, Sakamoto S, Kurosaki A, Kurihara Y, Satoh K, Usui Y, Nanki T, Arimura Y, Makino H, Okada Y, Harigai M, Yamagata K, Sugiyama H, Dobashi H, Ishizu A, Tsuboi N, Usui J, Sada KE, Homma S; for Japan Research Committee of the Ministry of Health, Labour, and Welfare for Intractable Vasculitis and Research Committee of Intractable Renal Disease of the Ministry of Health, Labour, and Welfare of Japan. Chest High-Resolution CT Findings of Microscopic Polyangiitis: A Japanese First Nationwide Prospective Cohort Study. AJR Am J Roentgenol. 2019 Jul;213(1):104-114. doi: 10.2214/AJR.18.20967. Epub 2019 Apr 11. PMID: 30973774. REFERENCE #3: Ando Y, Okada F, Matsumoto S, Mori H. Thoracic manifestation of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-related disease. CT findings in 51 patients. J Comput Assist Tomogr. 2004 Sep-Oct;28(5):710-6. doi: 10.1097/01.rct.0000135280.79012.c7. PMID: 15480049. DISCLOSURES: No relevant relationships by Kyle Halligan, source=Web Response No relevant relationships by Jennifer Kodela, source=Web Response

Myeloperoxidase and associated lung disease: Review of the latest developments.

Myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibodies (ANCA) are often detected in association with a variety of lung pathologies, the most common being interstitial lung disease (ILD). A growing cohort of patients are being diagnosed with MPO-ANCA in the context of ILD without ANCA-associated vasculitis. Clinically and radiologically, there is little to differentiate this cohort from MPO-ANCA-negative ILD patients; however, the pathophysiology is likely different and different treatments are likely required. We present here a brief summary of the proposed pathophysiology of MPO-ANCA-positive ILD, and a more detailed review of the latest evidence on management, including monitoring for development of ANCA-associated vasculitis, immunosuppression, anti-fibrotics, and novel agents that have yet to be trialled in human experiments.

Acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody following cimetidine treatment: a case report

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis usually induces rapidly progressive glomerulonephritis, including pauci-immune necrotizing crescentic glomerulonephritis. Acute tubulointerstitial nephritis (ATIN), which is often drug-induced, is a frequent cause of kidney injury. However, ATIN associated with ANCA without any glomerular lesions has been rarely reported, and drug-induced ATIN associated with ANCA is not well recognized. Here we present a case of an older woman with ATIN associated with myeloperoxidase-ANCA (MPO-ANCA) following cimetidine treatment.Case presentationA 70-year-old woman was admitted to our hospital due to acute kidney injury and mild proteinuria. She had a one-year history of chronic thyroiditis and dyslipidemia, for which she was taking levothyroxine sodium and atorvastatin, respectively. Two weeks before admission she had started cimetidine, methylmethionine sulfonium chloride, and itopride hydrochloride for gastric discomfort persistent since a month. She had experienced fatigue for two weeks and later appetite loss. The patient demonstrated a positive titer for MPO-ANCA (192 IU/mL) and a positive drug-induced lymphocyte stimulation test for cimetidine. She underwent two kidney biopsies that revealed ATIN without any glomerular lesions. Despite discontinuation of cimetidine on admission, renal injury continued with the presence of high MPO-ANCA titer. Oral steroid treatment was closely related with the recovery of her renal function and disappearance of MPO-ANCA.ConclusionsIn this case, ATIN presented as sustained renal insufficiency and high MPO-ANCA titer despite withdrawal of cimetidine. Therefore, we reason that the development of ANCA-associated ATIN was caused by cimetidine. Serologic follow-up with measurement of MPO-ANCA titers and renal biopsy are recommended when the clinical history is inconsistent with the relatively benign course of drug-induced ATIN.

Myeloperoxidase anti-neutrophil cytoplasmic antibody positive optic perineuritis after mRNA coronavirus disease-19 vaccine.

Myeloperoxidase anti-neutrophil cytoplasmic antibody positive optic perineuritis after mRNA coronavirus disease-19 vaccine.

Anti-neutrophil cytoplasmic antibody-associated vasculitis accompanied by type II heparin-induced thrombocytopenia resulting in asymptomatic cerebral infarction: a case report

BackgroundHeparin-induced thrombocytopenia (HIT) involves platelet activation and aggregation caused by heparin or HIT antibodies associated with poor survival outcomes. We report a case of HIT that occurred after hemodialysis was started for rapidly progressive glomerulonephritis (RPGN), which was caused by anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), and ultimately resulted in asymptomatic cerebral infarction.Case presentationA 76-year-old Japanese man was urgently admitted to our hospital for weight loss and acute kidney injury (serum creatinine: 12 mg/dL). Hemodialysis therapy was started using heparin for anticoagulation. Blood testing revealed elevated titers of myeloperoxidase anti-neutrophil cytoplasmic antibodies, and renal biopsy revealed crescentic glomerulonephritis with broad hyalinization of most of the glomeruli and a pauci-immune staining pattern. These findings fulfilled the diagnostic criteria for microscopic polyangiitis, and the patient was diagnosed with RPGN caused by AAV. Steroid pulse therapy, intermittent pulse intravenous cyclophosphamide, and oral steroid therapy failed to improve the patient’s renal function, and maintenance dialysis was started. However, on day 15, his platelet count had decreased to 47,000/µL, with clotting observed in the hemodialysis catheter. Magnetic resonance imaging of the head identified acute asymptomatic brain infarction in the left occipital lobe, and a positive HIT antibody test result supported a diagnosis of type II HIT. During hemodialysis, the anticoagulant treatment was changed from heparin to argatroban. Platelet counts subsequently normalized, and the patient was discharged. A negative HIT antibody test result was observed on day 622.ConclusionsThere have been several similar reports of AAV and HIT co-existence. However, this is a rare case report on cerebral infarction with AAV and HIT co-existence. Autoimmune diseases are considered risk factors for HIT, and AAV may overlap with other systemic autoimmune diseases. To confirm the relationship between these two diseases, it is necessary to accumulate more information from future cases with AAV and HIT co-existence. If acute thrombocytopenia and clotting events are observed when heparin is used as an anticoagulant, type II HIT should always be considered in any patient due to its potentially fatal thrombotic complications.

The impact of antineutrophil cytoplasmic antibody-associated vasculitis on employment and work disability in an Australian population.

Although antineutrophil cytoplasmic antibody-associated vasculitis (AAV) most commonly affects older individuals, many patients develop the disease during their most productive working years. The aim of this study was to examine the effects of AAV on employment and work disability in a cohort of Australian patients of working age. Patients attending a vasculitis clinic located in Melbourne, Australia, completed an employment questionnaire in addition to the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem. The average age of the 47 respondents was 47.8±11.9years (range 22-63years), with a median disease duration of 60months (range 10.2-318.5months). There were 68.1% who were currently employed, but 20.6% of respondents employed at the time of diagnosis were no longer working and 10.6% had experienced a significant reduction in work hours since their diagnosis. There were 12.7% who were dependent on the disability support pension. The rate of work disability was 23.4%. Many participants considered themselves work impaired (41.9%), with 10.1% having missed work in the previous week. Furthermore, 44.7% of respondents reported that their financial stability had been negatively impacted by their vasculitis diagnosis. Fatigue was commonly reported. Work disabled patients were significantly more likely to be obese and less likely to have completed a tertiary education. Work disabled patients tended to be older, myeloperoxidase-antineutrophil cytoplasmic antibody positive, and have renal involvement and lung involvement. A proportion of people living with AAV in Australia experience a decline in employment and an increase in work disability when living with this condition.

Should PLEX Be Used for Severe AKI and/or Pulmonary Hemorrhage in ANCA-Associated Vasculitis (AAV)? COMMENTARY.

“To plasmapherese (PLEX) or not to PLEX” is a question in the induction therapy for patients with ANCA-associated vasculitis (1). Drs. Glassock and Derebail present differing yet sometimes overlapping conclusions to this question in their virtual debate. Their erudite analysis carefully examines the available literature from their respective pro or con positions. To focus the issues, let us consider three real-life patients who illustrate the quandary of when, or whether, PLEX should be used. A 32-year-old mother of three is coughing up blood in the emergency room, complaining of worsening fatigue over the past 3 weeks. Physical examination 7 months prior was unremarkable; hemoglobin was 12.8 mg/dl, and serum creatinine was 0.7 mg/dl. Urinalysis was not performed. She describes new, dark, “tea-colored” urine over the past 2 days. Urinalysis shows numerous red blood cells and red cell casts. Kidney biopsy reveals pauci-immune necrotizing and crescentic glomerulonephritis (GN) with necrosis and crescents in three of seven glomeruli. There is minimal or no interstitial infiltrate, fibrosis, or tubular atrophy. Myeloperoxidase (MPO) ANCA is positive at a titer of 93 (normal <20). High-resolution chest computed tomography reveals diffuse alveolar infiltrates with minimal bronchial abnormalities involving multiple lung lobes. Oxygen saturation is 88% on 2 L of oxygen. The diagnosis is MPO ANCA with diffuse alveolar hemorrhage and necrotizing and crescentic GN. In addition to glucocorticoids and intravenous cyclophosphamide/rituximab, would you order plasmapheresis? Dr. Derebail would argue that this patient should receive plasmapheresis. Dr. Glassock specifies that no randomized, controlled trials of PLEX as therapy for diffuse alveolar hemorrhage are available and concludes that “PEXIVAS is not very informative regarding the utility of PLEX …

The misleading laboratory results: Renal impairment associated with high anti myeloperoxidase titer (anti-MPO) does not always mean ANCA vasculitis

Introduction: Antineutrophil cytoplasmic autoantibodies (ANCAs) are crucial in the pathogenesis of ANCA-associated glomerulonephritis. Although highly specific for this disease, these antibodies can appear in healthy individuals or occur in other settings such as malignance, other inflammatory disease, or drugs. Renal biopsy remains essential for diagnosis and as a prognostic tool. Failing to perform a biopsy risks an incomplete evaluation or misdiagnosis. Clinical case: A 60-year-old male known to have had previous normal kidney function was admitted with generalized pitting edema, nonpruritic erythematous rash, and decreased urine output. He had been recently started on clozapine for depression. Laboratory tests revealed nephrotic syndrome with massive proteinuria (11g/day), hematuria and elevated serum creatinine that reached a maximum of 4.9 mg/dl. The only positive finding was a high titer of myeloperoxidase (MPO) ANCA antibody (111 UI/ml). Clozapine was discontinued, and he was started on conservative management of the nephrotic syndrome. The rash disappeared within one week. Kidney biopsy showed cellular variant focal segmental glomerulosclerosis (FSGS) with mild acute tubular injury. The patient was treated with oral prednisolone with complete remission. Repeat MPO-ANCA was negative after one month. Discussion: We present a challenging case that highlights the importance of kidney biopsy for accurate diagnosis with major impact on treatment and prognosis. This case also underlines the presentation and evolution of FSGS cellular variant, a rare and poorly understood disease. The relationship between skin rash with high MPO titer and the administration of clozapine with clinical remission after its discontinuation favors the hypothesis of drug associated ANCA-vasculitis.

Improvement of Chronic Rhinosinusitis and Reduction of the Myeloperoxidase-Antineutrophil Cytoplasmic Antibody Titer in a Patient with Eosinophilic Granulomatosis with Polyangiitis by Additional Mepolizumab

A case of eosinophilic granulomatosis with polyangiitis (EGPA) in which chronic rhinosinusitis (CRS) was improved with a reduction in the myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) titer after the addition of mepolizumab is reported. A 55-year-old woman with EGPA receiving prednisolone 5 mg/day developed CRS with increases in the eosinophil count and the MPO-ANCA titer. Although it improved with prednisolone 15 mg/day in addition to mizoribine 150 mg/day, because azathioprine could not be taken orally due to side effects, it relapsed after prednisolone was tapered to 5 mg/day. There was no exacerbation of other vasculitis symptoms such as mononeuropathy multiplex. The patient was treated with additional mepolizumab 300 mg every 4 weeks, which resulted in the improvement of CRS and marked reductions of the eosinophil count and MPO-ANCA titer, and the reduction of prednisolone to 2 mg/day. Furthermore, even after tapering mepolizumab to 200 mg every 4 weeks, her condition remained stable without relapse of EGPA and without increases in the eosinophil count and MPO-ANCA titer. The clinical course of mepolizumab treatment in this patient suggests that the IL5-dependent inflammatory cascade is one of the factors contributing to the increase in MPO-ANCA in EGPA.

TIM-3 regulates the NETs-mediated dendritic cell activation in myeloperoxidase-ANCA-associated vasculitis.

T cell immunoglobulin and mucin domain 3 (TIM-3) has been reported as an important regulatory molecule on T cells and plays a pivotal role in autoimmune diseases, but the impact on dendritic cells (DCs) is poorly explored. The formation of neutrophil extracellular traps (NETs) is considered as strongly implicated in the pathogenesis of autoimmune diseases, such as in myeloperoxidase-antineutrophil cytoplasmic autoantibody associated vasculitis (MPO-AAV). This study thus aimed to investigate the potential regulation roles of TIM-3 in the regulation of NETs-mediated DC activation in MPO-AAV. Twenty untreated patients with MPO-AAV and 20 healthy controls were enrolled in this study. The expressions of TIM-3 and toll-like receptor 4 (TLR4) in peripheral blood dendritic cells were analysed by flow cytometry, and the release of NETs by neutrophils was evaluated by immunofluorescence. In animal experiments, we measured the DC activation markers after the stimulation of NETs. Furthermore, we detected the NETs-mediated DC activation after TIM-3 blockade. Here we found an increased spontaneous NET production in MPOAAV patients. We also revealed a markedly reduced expression of TIM-3 and an increased expression of TLR4 on DCs of active MPO-AAV patients. We found the NETs could induce the activation of DCs and promote Toll-like receptor 4 expression on DC surface. More interestingly, the blockade of TIM-3 could further enhance the NETs-mediated DC cytokine expression. Our results demonstrated DC surface TIM-3 plays an important role in maintaining the NETs mediated immune homeostasis in MPO-AAV, suggesting an important role in MPOAAV development.

Clinical Significance of Interstitial Lung Disease and Its Acute Exacerbation in Microscopic Polyangiitis

Presence of interstitial lung disease (ILD) is thought to be associated with mortality in microscopic polyangiitis (MPA); however, evidence on MPA-ILD remains lacking. Acute exacerbation (AE) refers to rapidly progressive, fatal respiratory deterioration that may develop in patients with various ILDs. No study has investigated the clinical significance of AE in MPA-ILD. We aimed to determine the clinical picture and prognostic factors, the incidence of AE, and the risk factors in patients with MPA-ILD. Eighty-four consecutive patients with MPA-ILD and 95 patients with MPA-non-ILD were analyzed. We also compared 80 patients with MPA-ILD and 80 patients with idiopathic interstitial pneumonia without myeloperoxidase-antineutrophil cytoplasmic antibody positivity (ILD alone), who were matched for age, sex, and chest high-resolution CT scan pattern. The MPA-ILD group had a higher frequency of men and smokers and was associated with higher mortality than the MPA-non-ILD group. The matched MPA-ILD group had a higher mortality rate than the matched ILD alone group. There was no significant difference in AE incidence between the matched MPA-ILD and ILD alone groups (1-year AE cumulative incidence rate, 7.5%and 5.2%, respectively; P= .75). In the MPA-ILD group, a lower percent predicted FVC (%FVC) was independently associated with a higher mortality rate (hazard ratio [HR], 0.96 per 1%increase; P< .01) and a higher AE incidence rate (HR, 0.96 per 1%increase; P= .01). On multivariable Cox regression analysis with time-dependent covariates, developing AE during their clinical course was strongly associated with shorter survival (HR, 17.1; P< .001). MPA-ILD represented a distinct phenotype with poor prognosis. Lower %FVC was an independent prognostic factor. Patients with lower %FVC had a risk of developing AE, which was a strong prognostic determinant. The specific management for MPA-ILD and AE should be established.

Atypical anti-glomerular basement membrane disease with anti-GBM antibody negativity and ANCA positivity: a case report

BackgroundAnti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disease that involves the lung and kidneys and leads to rapid glomerulonephritis progression, with or without diffuse alveolar hemorrhage, and even respiratory failure. Classic cases of anti-GBM disease are diagnosed based on the presence of the anti-GBM antibody in serum samples and kidney or lung biopsy tissue samples. However, atypical cases of anti-GBM disease are also seen in clinical practice.Case presentationWe herein report the rare case of a patient with atypical anti-GBM disease whose serum was negative for the anti-GBM antibody but positive for the myeloperoxidase (MPO) anti-neutrophil cytoplasmic antibody (p-ANCA) and another atypical ANCA. Laboratory test results showed severe renal insufficiency with a creatinine level of 385 μmol/L. Renal biopsy specimen analysis revealed 100% glomeruli with crescents; immunofluorescence showed immunoglobulin G (IgG) linearly deposited alongside the GBM. Finally, the patient was discharged successfully after treatment with plasmapheresis, methylprednisolone and prednisone.ConclusionThis patient, whose serum was negative for the anti-GBM antibody but positive for p-ANCA and another atypical ANCA, had a rare case of anti-GBM disease. Insights from this unusual case might help physicians diagnose rare forms of glomerulonephritis and treat affected patients in a timely manner.

Clinical Characteristics and Outcome of ANCA-Associated Vasculitis; Experience of A Single Reference Vasculitis Center

Objective: The aim of the study is to describe the clinical characteristics of Antineutrophil cytoplasmic antibodies-associated vasculitis and to analyze the parameters affecting the outcome.&#x0D; Materials and Methods: The study is a retrospective cohort study. Totally 130 patients with Antineutrophil cytoplasmic antibodies-associated vasculitis (18 years and over) who were followed up between October 2014 and October 2019 were analyzed. Demographic data, laboratory values, clinical course, thorax computed tomography findings and treatment approaches were noted from the charts of patients. Patients were divided into two groups as those with pulmonary involvement and non-pulmonary involvement.&#x0D; Results: We retrospectively reviewed the medical records of 130 patients with Antineutrophil cytoplasmic antibodies-associated vasculitis; 111 with granulomatosis with polyangiitis, 15 with microscopic polyangiitis, 1 with eosinophilic granulomatosis with polyangiitis, and 3 with other types of vasculitis. The ratio of having the abnormality in thoracic computed tomography was 72.2%. There were 84 cases with pulmonary involvement and 46 cases with non-pulmonary involvement. The frequency of microscopic polyangiitis was significantly higher (p=0.034) in non-pulmonary involvement cases.&#x0D; There were 67 cases with proteinase 3 Antineutrophil cytoplasmic antibodies and 39 cases with myeloperoxidase Antineutrophil cytoplasmic antibodies positivity. Most of the cases with proteinase 3 Antineutrophil cytoplasmic antibodies positivity were classified as granulomatosis with polyangiitis, this was statistically significant. Recovery was referenced for the outcome. Any of the variables were found statistically significant effective on outcome.&#x0D; Conclusions: Cases with pulmonary involvement were more than the cases without pulmonary involvement in our study. microscopic polyangiitis was significantly higher in non- pulmonary involvement cases. We studied on a large group, and these significant findings may have important implications for the investigation, pathogenesis, and treatment of Antineutrophil cytoplasmic antibodies-associated vasculitis.

Association between sinusitis and relapse and changes in the myeloperoxidase-antineutrophil cytoplasmic antibody in microscopic polyangiitis.

Previous studies have evaluated the risk factors for relapse of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and the biomarkers of AAV for predicting relapse. However, little is known about the association between the presence of sinusitis and relapse and changes in the ANCA levels in AAV. This single-center, retrospective cohort study included 104 consecutive patients who were newly diagnosed with myeloperoxidase (MPO)-ANCA-positive microscopic polyangiitis (MPA) between 2006 and 2018 and were treated at the Aichi Medical University Hospital in Japan. The relationships between sinusitis and relapse of vasculitis and elevated MPO-ANCA levels were assessed using multivariate Cox proportional hazards models that were adjusted for clinically relevant factors. During the entire follow-up period (median, 24 months; interquartile range, 7–54 months), 93 (89.4%) patients achieved remission. After achieving remission, 38 (40.9%) patients experienced at least one relapse (13 [65.0%] in the sinusitis group; 25 [34.3%] in the non-sinusitis group). Sinusitis was identified as a significant predictor of relapse (adjusted hazard ratio: 2.41, 95% confidence interval [CI]: 1.19–4.88; P = 0.015). Furthermore, sinusitis was more likely to be associated with elevated MPO-ANCA levels (adjusted hazard ratio: 2.59, 95% CI: 1.14–5.92; P = 0.024). In conclusion, sinusitis was associated with a higher risk of relapse and elevated MPO-ANCA levels in MPA patients, suggesting that careful management may be required to reduce the risk of relapse in patients with sinusitis. Further studies are needed to elucidate the optimal treatment strategy for these patients.