Anti-myeloperoxidase Antibodies Research Articles

Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/μl) (GPA HE) to develop a differentiating strategy. A retrospective analysis of the POLVAS registry. The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/μl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

An Unusual Presentation of Propylthiouracil-Induced Immunoglobulin A Vasculitis With Positive Anti-proteinase-3 and Anti-myeloperoxidase Antibodies

An Unusual Presentation of Propylthiouracil-Induced Immunoglobulin A Vasculitis With Positive Anti-proteinase-3 and Anti-myeloperoxidase Antibodies

Incidence of Systemic Vasculitis and Clinical Outcomes in Systemic Sclerosis: 2-Years Follow-Up of Asymptomatic Positive for Anti-Neutrophilic Cytoplasmic Antibody.

Anti-neutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) overlap with systemic sclerosis (SSc) is uncommon. We aimed to determine the incidence of AAV and define clinical outcomes relevant to asymptomatic screening positive for ANCA in SSc after 2 years of follow-up. The study was a cohort study of 185 Thai adult SSc patients testing for ANCA and having a 2-year follow-up at the Scleroderma Clinic, Khon Kaen University, Thailand. The incidence of AAV and outcomes of those who tested positive for ANCA were evaluated. A total of 185 SSc patients were tested for ANCA, of whom 21.6% were positive for either cytoplasmic ANCA, perinuclear ANCA (p-ANCA), anti-myeloperoxidase (anti-MPO), or anti-proteinase3 antibody. Only one 52-year-old female patient with dcSSc, negative for initial ANCA test, developed AAV (microscopic polyangiitis) 7 months after the first ANCA test for an incidence of AAV of 0.27 per 100-person-years (95% CI 0.01-1.5). She was positive for p-ANCA and anti-MPO. Eight of those who had an initial test were positive for ANCA and underwent a repeated test. Only two cases persisted as positive for ANCA (1 anti-MPO and 1 anti-PR3) and had no clinicals suspicious of vasculitis. Four cases that had ANCA turned to a negative result. AAV is a rare complication in SSc, so ANCA may not have any role as a screening test for AAV as it cannot predict the development of AAV in SSc. We suggest testing for ANCA only in SSc patients with clinicals suspicious of AAV.

Pathogenetic role of neutrophil extracellular traps in coronary flow impairment following percutaneous coronary intervention in acute myocardial infarction patients -A multicenter study-

Abstract Background A suicidal function of neutrophils to ensnare and kill microbes by expelling neutrophil extracellular traps (NETs) via histone citrullination and chromatin decondensation has emerged as it enhances local inflammation and thrombogenicity at the culprit lesion of acute myocardial infarction (AMI). Purpose This multicenter study was aimed to examine 1) the histopathological feature of coronary thrombus with the NETs formation in AMI patients, and 2) the association of NETs with impaired coronary flow after percutaneous coronary intervention (PCI) for AMI patients. Methods Coronary thrombi were obtained from 44 patients with AMI [male; 77%, age; 69±12(SD) y-o)]who underwent PCI within 24 hours from the onset. Aspirated thrombi were immediately bisected and frozen, and 5-µm thickness unstained sections were processed for polarized light microscopy (PLM) imaging and immunofluorescence staining. NETs were immunohistochemically defined when objects were co-stained with anti-myeloperoxidase and anti-citrullinated histone H3 antibodies (Figure A,B). Adjacent sections were stained with Masson’s trichrome to measure the whole thrombus area. The ImageJ1 software was utilized for the automatic segmentation on the digitized histology images. Segmented NETs area was divided by the thrombus area as a measure of NETs. Clinical characteristics, including AMI subset, post PCI final TIMI flow grade and TIMI frame count, were collected. Results All aspirated thrombi exhibited NETs (Figure A), and then subjects were split into 2 groups with a median value of NETs (62.8 x10-4 um2/um2); high-NETs and low-NETs groups. Patient characteristics were all comparable between the 2 groups. PLM results showed that birefringent crystals, suggestive of cholesterol crystals, were more frequently noted in the thrombi with high-NETs compared with those with low-NETs (50.0% vs. 13.6%, P=0.010). In the immunofluorescence, NETs were seen in the proximity of the crystals (Figure B). The multivariable analysis with covariates of age, sex, major coronary risk factors, MI related to left anterior descending artery and the onset to aspiration time revealed that the presence of birefringent crystals remained an independent predictor for high-NETs formation [OR=5.78, 95%CI=1.13-29.66, P=0.035]. In the high-NETs group, the prevalence of the final TIMI flow grade 3 was significantly lower than the low-NETs group (63.6% vs. 90.9 %, P=0.031). Likewise, there was a significant positive correlation between NETs area and TIMI frame count, defined as the number of cineframes required for contrast to reach a standardized distal coronary landmark (R=0.681, P&amp;lt;0.001). Conclusion The present study demonstrated that NETs were highly expressed in coronary thrombus aspirated from AMI patients in association with crystalline components, relating to coronary flow impairment following PCI in AMI patients.

Newly diagnosed ANCA-associated vasculitis after COVID-19 infection: a case report

BackgroundAntineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic autoimmune disease characterized by mononuclear cell infiltration and small and medium-sized blood vessel destruction leading to renal failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been shown to have the potential to induce the presentation or exacerbation of autoimmune disease. This report describes the clinical features of a case of newly diagnosed ANCA-associated vasculitis after COVID-19 Infection.Case presentationDuring the COVID-19 pandemic, a 67- year-old female Japanese was undergoing treatment for interstitial pneumonia, diabetes mellitus, and hypertension at her local doctor. About 2 months ago, she was diagnosed with COVID-19 and went to a hotel for treatment, and her condition improved. But a month later, after her COVID-19 infection, she presented with a fever and cough and visited Yodogawa Christian Hospital in Osaka, Japan. The reverse transcription-polymerase chain reaction was negative. She underwent extensive radiological and laboratory investigations. Serologies revealed a high perinuclear-ANCA titer with a specific anti-myeloperoxidase antibody titer of 31.7 units/mL. We suspected ANCA-associated vasculitis and performed a renal biopsy. Renal biopsy showed evidence of crescentic glomerulonephritis, which was consistent with ANCA-associated vasculitis. The patient was referred to the Department of Rheumatology and Clinical Immunology for steroid pulse and cyclophosphamide treatment.ConclusionsDelayed screening may lead to progression of the autoimmune disease, so prompt diagnosis is necessary. In this case, we could make an immediate diagnosis and refer the patient to the Department of Rheumatology and Clinical Immunology.

The onset of de novo autoantibodies in healthcare workers after mRNA based anti-SARS-CoV-2 vaccines: a single centre prospective follow-up study

Nowadays, data concerning the risk of autoimmune disease after SARS-CoV-2 (COVID-19) vaccination is controversial. The aim of this single centre prospective follow-up study was to evaluate whether healthcare workers (HCWs) vaccinated with BNT162b2 mRNA and mRNA-1273 will show a development and/or a persistence of autoantibodies, focussing on the detection of antibodies against nuclear antigens (antinuclear antibodies, ANA). We enrolled 155 HCWs, however only 108 of them received the third dose and were considered for further analysis. Blood samples were collected before vaccine inoculation (T0), at 3 (T1) and 12 months (T2) after the first dose. All samples were analysed for the presence of a) ANA using indirect Immunofluorescence [IIF] (dilutions of 1:80, 1:160. 1:320 and 1:640), and anti-smooth muscle antibodies (ASMA); b) anti-myeloperoxidase (anti-MPO), anti-proteinase 3 (anti-PR3) and anti-citrullinated peptide antibodies (aCCP) [FEIA]; c) anti-phospholipid antibodies (anticardiolipin [aCL], anti-beta-2- glycoprotein I [anti-ß-2GPI] (Chemiluminescence). Line-blot technology was performed using the following kit: EUROLINE ANA profile 3 plus DFS70 (IgG). Our research suggests that mRNA based anti-SARSCoV-2 vaccines can induce the production of de novo ANA in 22/77(28,57%) of subjects and that the percentage of positivity seems to be directly correlated to the number of vaccine expositions: 6/77 (7,79%) after 2 doses; 16/77 (20,78%) after 3 doses. Since it is known that hyperstimulation of the immune system could lead to autoimmunity, these preliminary results seem to further sustain the idea that the hyperstimulation of the immune system might lead to an autoinflammatory mechanism and eventually to autoimmune disorders. However, the link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated.

Antimyeloperoxidase antibodies modulate inflammatory responses and activate profibrotic pathways in human monocytes

Antimyeloperoxidase (anti-MPO) and antiproteinase 3 (anti-PR3) antibodies are found in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). We investigated the effect of both anti-MPO and anti-PR3 IgG on human monocytes. Peripheral blood monocytes were cultured under a range of conditions that included TLR agonists, anti-MPO IgG and anti-PR3 IgG with appropriate controls. Experiments included whole transcriptome profiling and an assessment of the role of Fc receptors.When monocytes were stimulated with LPS or R848, anti-MPO but not anti-PR3 IgG, caused a reduction in IL-10 secretion and had a profound effect on cell-surface marker expression. Anti-MPO but not anti-PR3 IgG enhanced monocyte survival in the absence of TLR stimulation. These effects depended on the Fc receptor CD32a. With TLR stimulation, the effect of anti-MPO but not anti-PR3 IgG on the transcriptional response at 6 h was variable, but we identified a core set of transcripts likely to be important. Without TLR stimulation, there was a robust effect of anti-MPO but not anti-PR3 IgG on the transcriptional response at 24 h, and there was a highly significant enrichment of genes encoding extracellular matrix and extracellular matrix-associated proteins. Analysis with nCounter confirmed many of the differentially expressed transcripts and supported a role for CD32a. These data show that anti-MPO, but not anti-PR3 IgG, from patients with AAV has wide-ranging effects on monocytes which depend on CD32a. The activation of a profibrotic transcriptional response by anti-MPO but not anti-PR3 IgG may give insights into the differences in disease phenotype.

P031 Montelukast antagonising underlying systemic illness

Abstract Background/Aims Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, multisystemic, autoimmune vasculitis involving small to medium-sized blood vessels. It has a well-established affiliation with atopic syndromes, typically adult-onset asthma and sinusitis. More rare associations are linked with drug side effects such as Montelukast. According to the ‘American College of Rheumatology 1990’, the following criteria yield a sensitivity of 84% in identifying a patient with EGPA. The criteria include: asthma, eosinophilia &amp;gt;10% on differential white cell count, mononeuropathy or polyneuropathy, transient pulmonary infiltrates on chest radiography, paranasal sinus abnormality, and blood vessel biopsy demonstrating extravascular eosinophilia, in a patient with symptoms of systemic vasculitis. The multisystemic involvement of EGPA makes both diagnosis and management difficult as presentations can vary. Methods We report the complex case of a 61 year-old gentleman diagnosed with EGPA. His relevant past medical history includes a diagnosis of Asthma in 2002 (managed with inhaled bronchodilators, corticosteroids, and montelukast), recurrent sinusitis, and lower respiratory tract infections. The patient presented with a one month history of abdominal cramping and bloating. This was associated with nausea, constipation, anorexia, and a week of ‘drenching’ night sweats. His full physical examination during this time was unremarkable. Results He had a normal CT Abdomen Pelvis and colonoscopy. His admission chest radiograph demonstrated bilateral parenchymal lung changes. This was followed by a CT Thorax showing bilateral upper and lower lobe bronchiectasis. Mediastinal and hilar adenopathy consistent with a diagnosis of allergic bronchopulmonary aspergillosis with associated reactive adenopathy. His laboratory investigations showed eosinophilia (21.68) and leucocytosis (32.7). In view of these results, an autoantibody screen was sent showing positive ANCA and positive anti-Myeloperoxidase antibodies(MPO titre 55). Two days into his admission he developed pain and paralysis of his right upper limb. He reported marked fatigue followed by a petechial, non-blanching, vasculitic rash on both ankles. Neurological examination reflected a subacute symmetrical sensory and motor polyneuropathy predominantly involving the right side with bilateral foot drop. MRI Brain demonstrated an established infarct in the left external capsule. He was commenced on high dose aspirin. Due to high suspicion for EGPA, methylprednisolone was commenced for 5 days, followed by tapering oral corticosteroid therapy and Rituximab therapy. A skin punch biopsy showed ‘ a vasculopathic type reaction with small vessel vasculitis, associated mixed inflammatory infiltrate which includes some eosinophils’ confirmed his diagnosis. Conclusion A topic of particular relevance to this case is the association between EGPA and montelukast. It has been hypothesised that there may be a relationship between Leukotriene Receptor Antagonist Therapy, specifically Montelukast, with the pathogenesis of EGPA. Some research suggests that treatment with Montelukast permits the decreased need for oral corticosteroids for asthma control. Therefore, suggesting that EGPA could have been masked by corticosteroid therapy. Disclosure Á. Connerton: None.

Spontaneous Corneal Perforation in Treatment-Resistant MPO-ANCA-Associated Small Vessel Vasculitis

Spontaneous corneal perforation is a rare complication in sterile ulcerative keratitis [1]. Identifying the systemic causes is essential for optimal treatment. Anti-myeloperoxidase antibodies (MPO) are a subcategory of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA). MPO-ANCA-associated small vessel vasculitis is a potential cause of sterile ulcerative keratitis. Being an autoimmune disorder, immunosuppressive therapy is indicated. Besides steroids, biologicals such as rituximab can be used with excellent results [2], [3].

Clinical and immunological variants of ANCA-associated systemic vasculitis: a look at the pulmonary fibrosis in microscopic polyangiitis with anti-myeloperoxidase antibodies and rheumatoid factor. Literature review and own observation

Depending on the epitope specificity of antineutrophil cytoplasmic antibodies (ANCA) and the presence or absence of a granulomatous inflammation. Patients with ANCA-associated vasculitis (AAV) show variability in clinical manifestations and prognosis depending on the epitope specificity of ANCA and the presence or absence of granulomatous inflammation. In this regard, it is important to identify the clinical and immunological phenotypes of AAV and a personalized approach to treatment. Microscopic polyangiitis (MPA) with antibodies to myeloperoxidase (aMPO) has a relatively high incidence of lung involvement and pulmonary fibrosis. We present our own clinical case of pulmonary fibrosis in MPA with aMPO and rheumatoid factor. Literature data are discussed. In cases of early arthritis and interstitial pneumonia, the possibility of AAV should be considered, a detailed examination is necessary to identify pathognomonic signs of AAV, including asymptomatic ones. Before prescribing immunosuppressants, the epitope specificity of ANCA should be determined. Treatment with rituximab, mycophenolate mofetil and nintedanib is discussed.

Microscopic Polyangiitis with an Atypical Presentation

Abstract Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic autoantibody-associated vasculitis, usually affecting the small vessels in the form of systemic necrotizing vasculitis. It commonly manifests as diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis but may present with the involvement of multiple organs. Timely diagnosis at an early localized stage is crucial for instituting an early disease-specific treatment. We report a case of a 63-year-old female who was diagnosed with MPA predominantly involving lungs and middle ears. The absence of a typical pulmonary–renal presentation and clinical features favoring obstructive airway disease and tuberculosis led to a delayed diagnosis. The presence of antimyeloperoxidase antibodies in high titer and a clinical response to monoclonal antibody therapy, thereby confirming the diagnosis of MPA prompted us to report this case.

Improvement of indirect immunofluorescence technique to detect antineutrophil cytoplasmic antibodies and its impact on test positivity rate.

The indirect immunofluorescence (IIF) technique for antineutrophil cytoplasmic antibodies (ANCA) detection is subject to substantial differences across laboratories. This study aimed to assess the impact of improvements in the IIF-ANCA technique on the positivity rate of ANCA tests. A cross-sectional study was performed with serum samples from patients with ANCA-associated vasculitis (AAV), autoimmune hepatitis (AIH), and ulcerative colitis (UC). A paired analysis was performed for IIF-ANCA results using the traditional method and a modified protocol after a series of specific adjustments in the technique based on the protocol of IIF-ANCA test performed at a nation-wide private laboratory in Brazil. ANCA specificity was assessed by ELISA for anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies. Sixty-one patients were evaluated. The positivity rate of IIF-ANCA tests at disease presentation performed at the University reference laboratory was 32.3% in AAV, AIH, and UC patients, whereas the positivity rates of IIF-ANCA and ELISA tests in other laboratories were 75.0 and 72.7%, respectively. After modifications in the IIF-ANCA technique, there was a significant increase in the positivity rate (14.8 vs 34.3%; P=0.0002) and in median titers [1/40 (1/30-1/160) vs 1/80 (1/40-1/80); P=0.0003] in AAV, AIH, and UC patients. UC had the highest increment in positive results from 5.3 to 36.8%. There was poor agreement between MPO- or PR3-ANCA and both IIF-ANCA techniques. In conclusion, modifications in the IIF-ANCA protocol led to a significant improvement in its positivity rate and titers.

Evaluation of diagnostic efficacy of digital liquid chip method for detection of specific antineutrophil cytoplasmic antibodies

To explore the clinical diagnostic efficacy of antineutrophil cytoplasmic antibody associated vasculitis (AAV) by comparing the consistency and coincidence rate of serum anti-myeloperoxidase (MPO) antibody and anti-protease 3 (PR3) antibody detected by digital liquid chip method (DLCM) and enzyme-linked immunosorbent assay (ELISA). To provide reference for the selection of detection methods of anti-MPO antibody and anti-PR3 antibody in clinical laboratory. This study is a cross-sectional study, a total of 307 cases of antineutrophil cytoplasmic antibodies were detected in the Department of Clinical Immunology, West China Hospital of Sichuan University from January to March 2021. The serum samples and related clinical information were collected. At the same time, the levels of anti-MPO antibody and anti-PR3 antibody in serum samples were detected by ELISA and DLCM, indirect immunofluorescence (IIF) was used to re-test the differential samples between the two methods. SPSS 26.0 was used to analyze the test results, Cohen's kappa coefficient analysis was used to compare the consistency of the two methods, and paired chi-square test was used to compare the sensitivity and specificity of the two methods to AAV. The results showed that the positive cases of anti-MPO antibody detected by ELISA and DLCM were 63 and 44, and the negative cases were 244 and 263; the positive cases of anti-PR3 antibody detected by ELISA and DLCM were 34 and 28, and the negative cases were 273 and 279. The results of anti-MPO antibody and anti-PR3 antibody detected by the two methods had good consistency and coincidence rate, in which the total coincidence rate of anti-MPO antibody was 92.51%, the positive coincidence rate was 66.67%, and the negative coincidence rate was 99.18%. The results of consistency analysis showed that kappa=0.741 had well consistency. The total coincidence rate of anti-PR3 antibody is 96.74%, the positive coincidence rate is 76.47%, and the negative coincidence rate is 99.27%. The consistency analysis results show that kappa=0.821 had strong consistency. The results of IIF re-test of differential samples showed that the coincidence rate between DLCM and IIF was higher. The results of comparative analysis of anti-MPO antibody and anti-PR3 antibody showed that the specificity of DLCM was better than that of ELISA, and its sensitivity was lower than that of ELISA. In conclusion, the results of anti-MPO antibody and anti-PR3 antibody detected by DLCM were consistent with those of ELISA. In the combined detection of anti-MPO antibody and anti-PR3 antibody, the specificity of DLCM is better than that of ELISA.

S66 Leukocytoclastic Vasculitis in a Crohn’s Disease patient with recent Sars-CoV2 infection

Case: Prior to the COVID-19 pandemic, leukocytoclastic vasculitis (LCV) had been described in association with a variety of chronic infections, autoimmune disorders, and medications. In the inflammatory bowel diseases (IBD) population, LCV has been reported as a rare cutaneous, extraintestinal manifestation, which may be related to the disease itself or associated with the use of biologic medications, particularly those that target tumor necrosis factor. Several cases of LCV related to infection with SARS-CoV2, not related to IBD, have been reported. We present a case of LCV in a woman with Crohn’s Disease (CD) who was on long-term maintenance infliximab and presented with purpuric papules on bilateral lower extremities shortly after infection with SARS-CoV2. A 37-year-old female with a 26-year history of ileocolonic CD in remission for at least 2 years presents to our IBD clinic with concern of rash on both lower extremities, accompanied by significant ankle pain. She had been on infliximab for 10 years. The symptoms began 1 month prior, 2 months after being diagnosed with COVID-19. She denied any concurrent GI symptoms that were new or worsened from her baseline. Lab evaluation was notable for positive ANA, elevated to 1:160. She had normal ANCA, anti-myeloperoxidase antibody, anti-dsDNA antibody, total IgG and total IgM, and rheumatoid factor. Skin punch biopsy showed fibrinoid necrosis of capillary walls within the dermis with surrounding neutrophils and karyorrhectic debris, findings consistent with LCV. Colonoscopy showed complete endoscopic remission of CD. An oral steroid taper lead only to temporary improvement and symptoms recurred at a dose of 10 mg prednisone. Due to suspicion of infliximab-associated LCV, infliximab was discontinued, and ustekinumab therapy was initiated. She was able to taper off steroids, and the rash completely resolved. LCV falls within a general category of cutaneous small vessel vasculitis; it is limited specifically to the skin, with no systemic or renal involvement. Patients typically present with palpable purpura, at times associated with urticaria. When IBD patients present with these findings, providers should review recent infectious symptoms, medication changes or drug exposure. Direct immunofluorescence should be performed on skin biopsy for lesions lasting >= 4 weeks. For symptoms < 4 weeks, conservative therapy with oral anti-histamine, and compression stockings have been effective. Implicated drugs should be stopped. For severe cases, systemic therapy with prednisone is recommended; dapsone or colchicine have also been used. When LCV has been discovered in the setting of COVID infection, treatment approaches have been varied, including topical and oral steroids, low molecular weight heparin, and intravenous immunoglobulin (IVIG). Prior to this case, there has been one case describing successfully treatment of LCV in CD with IVIG. Because this is a rare entity, no randomized controlled trials have been performed to evaluate safety or efficacy of specific therapies. While rare, LCV is an important pathology that IBD providers should be comfortable diagnosing and may only increase as COVID-19 remains common. Importantly, we must be aware that management of LCV will likely involve change in therapy for IBD, as medications are often implicated.

Anti-glomerular basement membrane disease developing 3years after the development of Sweet syndrome and 1year after the development of anti-neutrophil cytoplasmic antibody-associated vasculitis: a case report.

A 73-year-old Japanese woman, with a history of Sweet syndrome diagnosed 3years earlier and anti-myeloperoxidase (MPO) antibody anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis diagnosed 1year earlier, presented with an episode of rapidly progressive glomerulonephritis (RPGN) with anti-glomerular basement membrane (GBM) disease. At the time of diagnosis of the ANCA-associated vasculitis 1 year earlier, serological testing yielded a negative result for anti-GBM antibody. However, at the present visit, serology for anti-MPO antibody was negative, while that for anti-GBM antibody was positive. This is the first report of anti-GBM disease developing sequentially after Sweet syndrome and ANCA-associated vasculitis. This case may provide clues to the potential immunological links among these three distinct conditions.

SMALL VESSELS, BIG PROBLEMS: MICROSCOPIC POLYANGIITIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

SMALL VESSELS, BIG PROBLEMS: MICROSCOPIC POLYANGIITIS PRESENTING AS DIFFUSE ALVEOLAR HEMORRHAGE

A CASE OF MICROSCOPIC POLYANGIITIS (MPA) FOLLOWING SARS-COV-2 INFECTION

A CASE OF MICROSCOPIC POLYANGIITIS (MPA) FOLLOWING SARS-COV-2 INFECTION

CASE OF PULMONARY-RENAL SYNDROME SECONDARY TO HYDRALAZINE-INDUCED ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA)-VASCULITIS

CASE OF PULMONARY-RENAL SYNDROME SECONDARY TO HYDRALAZINE-INDUCED ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCA)-VASCULITIS

Review of systemic sclerosis and antineutrophil cytoplasmic antibody vasculitis overlap: Using autoantibodies for a personalised medicine approach.

Both antineutrophil cytoplasmic antibody-associated vasculitis and systemic sclerosis are rare autoimmune diseases. Both have the potential for significant multi-organ involvement, and both carry high morbidity and mortality. Disease-specific autoantibodies in these conditions allow for risk stratification for organ-based complications, and for personalised therapeutic strategies. The concomitant presentation of antineutrophil cytoplasmic antibody-associated vasculitis and systemic sclerosis is rare, and only reported in up to 1.3% of systemic sclerosis cases. These patients present more frequently with anti-myeloperoxidase and anti-topoisomerase antibody profiles, with increased incidence of interstitial lung disease and renal involvement than would be expected in either disease independently. Appreciating the role of the autoantibodies in each disease state, and where they overlap, allows for the potential of a more personalised approach to managing these complex patients.

Myeloid expression of the anti-apoptotic protein Mcl1 is required in anti-myeloperoxidase vasculitis but myeloperoxidase inhibition is not protective

Antibodies to neutrophil and monocyte myeloperoxidase and proteinase 3 are a feature of anti-neutrophil cytoplasmic antibody vasculitis, a disease with significant morbidity for which new treatments are needed. Mice with a myeloid-specific deletion of the anti-apoptotic protein Mcl1 have reduced numbers of circulating neutrophils. Here, we assessed if myeloid-specific Mcl1 was required in murine anti-myeloperoxidase vasculitis and whether inhibition of myeloperoxidase was protective. In a murine model of anti-neutrophil cytoplasmic antibody vasculitis, induced by anti-myeloperoxidase antibody, mice with a myeloid-specific deletion of Mcl1 were protected from disease. They had fewer crescents, neutrophils, and macrophages in the glomeruli, lower serum creatinine levels and reduced albuminuria compared with controls. At baseline and day six after disease induction they had fewer circulating neutrophils than controls. At day six there were also fewer circulating monocytes. Myeloperoxidase inhibition with AZD5904 had no effect on histological or biochemical parameters of disease, and there was also no reduction in albuminuria at day one, two, five or seven after disease induction. These findings persisted when disease was induced without granulocyte-colony stimulating factor, which increases disease severity. A second myeloperoxidase inhibitor, AZM198, also showed no evidence of an effect, although both AZD5904 and AZM198 inhibited human neutrophil extracellular trap formation invitro. Thus, our results show that while myeloid-specific Mcl1 is required in this model of anti-myeloperoxidase vasculitis, myeloperoxidase inhibition is not protective.