Antineutrophil Cytoplasmic Autoantibodies Research Articles

Microscopic polyangiitis plasma-derived exosomal miR-1287-5p induces endothelial inflammatory injury and neutrophil adhesion by targeting CBL.

An inflammatory environment around the vessel wall caused by leukocyte infiltration is one of the characteristic histopathological features of microscopic polyangiitis (MPA); however, the pathogenic mechanisms are not fully understood. Studies have found that circulating microRNA (miRNA) can be used as potential biomarkers for the diagnosis and classification of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV), and the E3 ubiquitin ligase casitas B-lineage lymphoma (CBL) seems to be associated with inflammation. In addition, evidence indicates that miRNA can be tracked into exosomes and transferred into recipient cells to mediate the process of vascular endothelial injury. Herein, we aimed to identify the profiles of exosomal miRNA, and determine the effect of exosomal miR-1287-5p and its target gene CBL on vascular endothelial cells in MPA. We isolated plasma exosomes from patients with MPA (MPA-exo) and healthy controls (HC-exo) by ultracentrifugation and conducted exosome small-RNA sequencing to screen differential miRNA expression in MPA-exo (n=3) compared to HC-exo (n=3). We measured the expression levels of miR-1303, miR-1287-5p, and miR-129-1-3p using quantitative reverse transcription-polymerase chain reaction (qRT-PCR, n=6) and performed dual luciferase reporter gene assays to confirm the downstream target gene of miR-1287-5p. In addition, we treated human umbilical vein endothelial cell (HUVEC) with MPA-exo, or transfected them with miR-1287-5p mimic/inhibitor or with CBL-siRNA/CBL-siRNA+ miR-1287-5p inhibitor. After cell culture, we evaluated the effects on vascular endothelial cells by examining the mRNA levels of IL-6, IL-8, MCP-1, ICAM-1 and E-selectin using qRT-PCR and performed neutrophil adhesion assay with haematoxylin staining. Transmission electron microscopy, Western blot and nanoparticle tracking analysis showed that we successfully purified exosomes and MPA-exo could be absorbed into HUVEC. We screened a total of 1,077 miRNA by sequencing and observed a high abundance of miR-1287-5p in the exosomes obtained from MPA plasma. The dual luciferase reporter assay identified CBL as a downstream target gene of miR-1287-5p, and the results revealed that MPA-exo decreased CBL protein expression in HUVEC. In addition, treatment with MPA-exo, up-regulating miR-1287-5p or silencing of CBL in HUVEC significantly increased the mRNA expression of inflammatory factors (including IL-6, IL-8, and MCP-1) and adhesion molecules (including ICAM-1 and E-selection) and promoted the adhesion of neutrophils to HUVEC. However, down-regulating miR-1287-5p had the opposite effect. Our study revealed that MPA-exo was involved in the intercellular transfer of miR-1287-5p and subsequently promote the development of acute endothelial injury in MPA. MiR-1287-5p and CBL agonists may be promising therapeutic approach for MPA-induced vascular inflammatory injury.

Double-Positive Anti-Glomerular Basement Membrane Antibody and Myeloperoxidase Antineutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis Post COVID-19 mRNA vaccine: A Case Series of 4 Patients.

Vaccines remain central to the management of COVID-19 pandemic, including the need for repeat doses of vaccines to boost immunity. There has been an accumulating case count of glomerulopathies temporally associated with COVID-19 vaccination. This case series presents 4 patients who developed double-positive anti-glomerular basement membrane antibody (anti-GBM) and myeloperoxidase (MPO) antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis after COVID-19 mRNA vaccination. This report contributes to our collective knowledge about the pathophysiology and clinical outcomes associated with this rare complication. Four patients developed nephritic syndrome within 1 to 6 weeks after receiving a COVID-19 mRNA vaccine (3 post Pfizer-BioNTech and 1 post Moderna vaccination). Three of the 4 patients also had hemoptysis. Three of the 4 patients had double-positive serology, whereas the fourth patient had renal biopsy findings consistent with double-positive disease, although anti-GBM serology was negative. All patients had renal biopsy findings consistent with double-positive anti-GBM and ANCA-associated glomerulonephritis. All 4 patients were treated with pulse steroids, cyclophosphamide, and plasmapheresis. Of the 4 patients, 1 demonstrated complete remission, 2 remained dialysis-dependent, and the fourth is deceased. Of the 2 patients who received repeat vaccination with COVID-19 mRNA vaccine, 1 patient had second serologic flare of anti-GBM in response to the vaccine. This case series reinforces growing evidence that COVID-19 mRNA vaccine-induced glomerulonephritis is a rare but real phenomenon. Dual ANCA and anti-GBM nephritis can present after the first dose of COVID-19 mRNA vaccine or after several administrations of the vaccine. We are the first to report cases of double-positive MPO ANCA and anti-GBM nephritis after Pfizer-BioNTech vaccination. To our knowledge, we are also the first to report outcomes of repeat COVID-19 vaccination in patients with de novo flare of ANCA and anti-GBM nephritis temporally associated with COVID-19 vaccination.

Granulomatosis with polyangiitis: what's new?

Within the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (GPA) is the most frequent. The incidence is around 10 to 20 cases/million/year. Clinical manifestations are varied, with ENT, lungs and kidneys most frequently involved. ANCA are pathogenic by triggering neutrophil activation, which leads to vascular damage. Detection of ANCA is most helpful in establishing the diagnosis, but serology may be negative in GPA limited to the airways. Diagnostic work-up and therapy require a multidisciplinary approach. Treatment includes an induction and maintenance phase, combining corticosteroids and immunosuppressive drugs. It aims at limiting the risk of relapses, which is important in GPA, and at reducing corticosteroids toxicity.

A Case of De Novo Antineutrophil Cytoplasmic Autoantibody Associated Glomerulonephritis Following ChAdOx1 Vaccination in an Indian Metropolitan City

Glomerulonephritis following the administration of vaccines for Severe acute respiratory syndrome coronavirus-2 has been reported worldwide. We present a case of de novo antineutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis following the administration of the ChAdOx1 vaccine, who presented with dyspepsia, pedal edema, raised creatinine, and proteinuria. Kidney biopsy showed pauci-immune ANCA-associated nonnecrotizing glomerulonephritis. The patient received corticosteroids and rituximab. The patient showed clinical improvement and normalization of renal parameters.

A challenging case of granulomatosis with polyangiitis with cardiac involvement: a rare case report

Granulomatosis with polyangiitis (GPA), a systemic antineutrophil cytoplasmic antibody (ANCA) associated vasculitis, is characterized by inflammation of the small arteries, arterioles, and capillaries classically manifesting with glomerulonephritis and necrotizing granulomatous lesions of the upper and lower respiratory tract. With an incidence of approximately 12 cases per one million individuals per year it is an uncommon diagnosis that typically presents as frequent pulmonary and sinus infections; however, if left without definitive treatment progresses to more severe manifestations specifically hemoptysis and hematuria. This case report highlights a 15-year-old woman who had both classic and non-classic findings making the diagnosis challenging. Specifically, her age of presentation, improvement with anti-microbials, and coronary dilation were not classic. Additionally, her lab work was negative for the cytoplasmic subset antineutrophil cytoplasmic autoantibody (c-ANCA), but positive for serum anti-proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA) which further delayed the ultimate diagnosis as this is typically c-ANCA positive. Other systemic vasculitides, such as mucocutaneous lymph node disease, are associated with cardiac pathology necessitating further medical management and follow-up to prevent increased morbidity and mortality. Knowing this, we conclude that further evaluation for cardiac pathology would be prudent as part of the initial workup of patients with a diagnosis of GPA. Included is a brief review of available literature on GPA to emphasize the typical presentation, lab findings, and importance of early diagnosis.

Avacopan for the treatment of ANCA-associated vasculitis: an update

ABSTRACT Introduction Glucocorticoids (GC) have been part of the standard treatment of anti-neutrophil cytoplasm autoantibodies (ANCA)-associated vasculitides (AAV) for more than 60 years. Various therapeutic advances have occurred over the past 2 decades and led to a significant reduction of GC exposure, but most patients still have to suffer from complications of GC, including infections, metabolic abnormalities, and cardiovascular morbidity. In 2007, activation of the complement pathway was demonstrated to play a role in the pathogenesis of AAV. Avacopan, an oral competitive inhibitor of the C5a receptor (C5aR1, CD88), was then developed, with an additional aim to decrease the use of GC. Areas covered In this article, we briefly summarize the rationale for targeting the complement pathway in AAV, and review relevant findings from pre-clinical, phase I, II, and III studies, subsequent and more recent case reports and series on the efficacy and safety of avacopan. Expert opinion Based on the results of these studies, avacopan was approved in most countries since late 2021, as an adjunctive induction treatment for patients with AAV. Several newer questions now are pending answers, including as to how avacopan should be used in real-world practice, beyond how it was given in the original clinical trials.

Autoimmunity in Infection-Related Glomerulonephritis

Introduction: Autoimmune (AI) reactivity in the setting of infection-related GN (IRGN) is often viewed as an epiphenomenon and is not well described. Methods: We report a cohort of 17 patients with IRGN during a 7-year period that highlights cases with AI reactivity and describes the clinical and pathologic characteristics of IRGN cases associated with AI reactivity. Results: Of the IRGN cases, 76% had clinical evidence of an autoimmune disease (AD) and/or positive AI serologies. Within the IRGN group with AI reactivity, 12 had positive AI serologies (92%) and 10 had AD (77%). 30% had a prior diagnosis of AD, while the remaining 70% did not have a history of AD and were either diagnosed or suspected of having an AD at the time of biopsy. The most common autoantibody detected was anti-nuclear antibody followed by anti-neutrophil cytoplasmic antibodies and autoantibodies associated with antiphospholipid syndrome. Conclusion: The study is not sufficiently powered to determine any significance but demonstrates the frequency with which AI features occur in IRGN and should prompt further future investigation. In summary, our findings suggest AI manifestations are common in IRGN.

Targeted inhibition of FcRn reduces NET formation to ameliorate experimental ulcerative colitis by accelerating ANCA clearance.

Dysregulated immune responses have now been recognized as an essential stimulator of ulcerative colitis (UC). Neutrophil extracellular traps (NET) were reported as the potential factor in sustaining mucosal inflammation in UC. NET formation further induces antineutrophil cytoplasm autoantibodies (ANCA) that serve as a biomarker in determining the severity of UC, which have a long half-life due to neonatal Fc receptor (FcRn)-mediated recycling. This study aimed to explore the role of the ANCA-NET cycle in UC and evaluate the potential of targeting FcRn in UC treatment. Dextran sodium sulfate-induced mice and rat models were used in this study. anti-rat FcRn monoclonal antibodies were used to block FcRn function in vivo. Disease activity index (DAI) and histopathological score (HS) were estimated to characterize the inflammation severity of UC. Serum concentrations of IgG, ANCA, TNF-α, IL-1β and CRP were measured using specific ELISA kits. Colonic NET-associated protein (NAP) expression was determined by western blotting. Serum ANCA and colonic NAPs showed a positive correlation that varied with changes in serum inflammation-related indexes (IRI; including TNF-α, IL-1β, and CRP) and DAI and HS in mice with UC. Blockade of FcRn significantly reduced serum ANCA levels and colonic NAP expression and effectively decreased serum IRIs, DAI, and HS in rats with UC. Especially during the inflammation recurrence period, blockade of FcRn exerted even better therapeutic effects in rats with UC than salazosulfapyridine. Our results show that anti-FcRn therapy has benefits in UC treatment through reduced colonic NET formation by accelerating serum ANCA clearance.

The Presence of ANCA in IgA Crescentic Nephropathy Does Not Lead to Worse Prognosis with Intensive Rescue Treatment

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The concomitant presence of both crescentic proliferation and anti-neutrophil cytoplasmic autoantibodies (ANCA) in this pathology represents a rare coincidence. However, it is not clear to what extent the presence of ANCA (IgA or IgG) in these patients could have any clinical significance. The aim of the current work is to describe the presence of ANCA (IgA or IgG) in patients with IgAN and crescentic proliferation and its possible clinical implications. We retrospectively recruited all patients in our center with a histological diagnosis of IgAN with crescentic proliferation between January 2013 and December 2020. The main demographic and clinicopathologic data, fundamental histological characteristics, as well as the treatments implemented and main kidney outcomes, were collected and analyzed at a 6 and 12-month follow-up. Between January 2013 and December 2020, a total of 17 adults were diagnosed with concomitant crescentic proliferation through a kidney biopsy of IgAN. Five (29.4%) patients showed ANCA, three (60%) showed IgA-ANCA and two (40%) showed IgG-ANCA. All ANCA-positive patients had some degree of crescentic proliferation. At diagnosis, the mean age of patients was 48 years old (range: 27-75). Nine of them were women (52%) and the most common clinical presentation was hypertension (71%). At the time of biopsy, the mean serum creatinine and proteinuria were 2.2 mg/dL (DS 1.42) and 3.5 g/mgCr (DS 1.22), respectively, with no statistical differences between ANCA-positive and -negative patients. Histological analyses showed that 11 out of the 12 (91%) ANCA-negative IgAN patients displayed less than 25% cellular crescents, whereas 100% of ANCA-positive IgAN patients displayed more than 25% cellular crescents (p = 0.04). Notably, five (30%) patients displayed fibrinoid necrosis, with four of them (80%) being IgAN-ANCA-positive (p = 0.01). Only one ANCA-negative patient needed renal replacement therapy (RRT) upon admission (5%). The mean serum creatinine and proteinuria were 1.94 mg/dL (DS 1.71) and 1.45 g/gCr (DS 1.78), respectively, within 6 months of immunosuppressive therapy. At 12-month follow-up, the mean creatinine was 1.57 mg/dL (DS 1). Four (23.5%) patients needed RRT at the end of the follow-up and four (23.5%) patients died. Probably due to the limited number of IgAN-ANCA-positive and IgAN-ANCA-negative patients, no significant differences were found between the clinical and laboratory characteristics. IgAN-ANCA-negative patients seemed to display less extracapillary proliferation than IgAN-ANCA-positive patients, who tended to show significantly higher fibrinoid necrosis. There were no differences regarding renal prognosis and patient survival after aggressive immunosuppressive therapy within 6 and 12 months when comparing the two samples.

Neurogenic intermittent claudication caused by vasculitis in the cauda equina: an autopsy case report.

Intermittent claudication (IC) refers to leg pain that is induced by walking and relieved by rest. Neurogenic IC is usually associated with lumbar canal stenosis (LCS). We present rare findings from an autopsied patient who had neurogenic IC caused by vasculitis in the cauda equina. We performed antemortem neurological and electrophysiological assessments, sural nerve biopsy, and post-mortem examination of the spinal cord and brain. A 61-year-old man noted sudden-onset leg pain that was not associated with any traumatic trigger. His leg pain consistently appeared when the patient walked and quickly faded on stopping. Spine surgery and cardiovascular departments both made a diagnosis of IC. However, magnetic resonance imaging (MRI) did not show LCS, and all ankle-brachial pressure indices were normal. He subsequently developed diffuse muscle weakness of the legs a month after disease onset. Myeloperoxidase antineutrophil cytoplasmic autoantibody was seropositive (140IU/mL), and a sural nerve biopsy revealed axonal injury and angiitis. MRI showed multiple cerebral infarctions. He was diagnosed with microscopic polyangiitis (MPA) and underwent corticosteroid therapy. He died from complications two months after the onset. A post-mortem study revealed vasculitis in the subarachnoid space of the cauda equina, spinal cord, and brain parenchyma. The cauda equina showed a combined loss of small and large axonal fibres. The lumbar cord displayed central chromatolysis of the lower motor neurons. MPA is a rare cause of neurogenic IC when the symptom is acute and multimodal. Small-vessel vasculitis affecting the cauda equina may underlie MPA-associated IC.

Granulomatous myopathy: Sarcoidosis and beyond.

Non-necrotizing granulomatous inflammation is a rare but easily recognized histopathological finding in skeletal muscle biopsy. A limited number of diseases are known to be associated with non-necrotizing granulomatous myopathy. Once identified, a careful evaluation for evidence of extramuscular granulomatosis and other signs suggestive of sarcoidosis is warranted as about half of the patients have sarcoid myopathy. In addition, the presence of granulomatous myopathy should trigger a search for clinical and pathological clues of inclusion body myositis (IBM), which accounts for most of the remaining patients and can coexist with sarcoidosis. Recognizing the features of IBM in patients with granulomatous myopathy can potentially spare the patients from unnecessary exposure to immunosuppressive therapies. In patients whose granulomatous myopathy remain unexplained, further investigations should aim at identifying myasthenia gravis and other autoimmune disorders, especially those known to cause granulomatous inflammation in other organs. Laboratory investigations should include acetylcholine receptor, antimitochondrial, antineutrophil cytoplasmic, thyroglobulin, and thyroid peroxidase autoantibodies. In the appropriate clinical context, exposure to immune checkpoint inhibitors and chronic graft-vs-host disease can be causes of granulomatous myopathy. In cases of unexplained granulomatous myopathy, natural killer/T-cell lymphoma should be considered and careful histopathological examination for atypical cells and appropriate immunostaining is crucial. Identifying the etiology of granulomatous myopathy in each patient can guide appropriate treatment.

A rare case of infliximab induced myeloperoxidase-cytoplasmic antineutrophil cytoplasmic autoantibody positive cutaneous vasculitis

<p>Drug-induced cutaneous vasculitis is a known autoimmune complication of tumor necrosis factor (TNF) inhibitors with many instances resulting in the production of newly formed antibodies. We report a 21-year-old female with a past medical history of Crohn’s disease controlled with infliximab who presented to dermatology with a purpuric rash and crusted plaques of her distal lower extremities. Biopsy of a lesion revealed perivascular lymphocytes, neutrophils and eosinophils, vessel wall damage, and dermal eosinophils consistent with a drug-induced vasculitis. Follow up labs assessing for antibodies revealed unusual findings of an elevated cytoplasmic-antineutrophil cytoplasmic autoantibody (C-ANCA) titer and myeloperoxidase (MPO) antibody level making this patient MPO-C-ANCA positive. The patient’s lesions were treated with both oral and topical steroids, colchicine, and transition of her infliximab to ustekinumab with subsequent improvement of her lesions and normalization of antibody titers.</p>

Multiple cerebral arterial dissections with a ruptured blister aneurysm after COVID-19 vaccination: a case report

Although extensive clinical data have verified the safety and adverse effects of coronavirus disease 2019 (COVID-19) vaccines, unexpected neurovascular events have rarely been reported. This report presents an unusual case in which we inferred that spontaneous multiple cerebral arterial dissections with a ruptured blister aneurysm occurred after COVID-19 vaccination. A 34-year-old woman presented with a severe headache, confusion, and mild weakness in her left arm 18 days after having received the Pfizer-BioNTech COVID-19 vaccine. Digital subtraction angiography showed fusiform dilatation in the proximal part of the left vertebral artery and luminal irregularities and string signs in the distal V4 segment. Stroke after vaccination involving multiple cerebral arterial dissections and simultaneous rupture of a blister aneurysm is a very rare phenomenon. Although laboratory studies such as cytoplasmic anti-neutrophil cytoplasmic autoantibody, perinuclear anti-neutrophil cytoplasmic antibodies, anti-cardiolipin, rheumatoid factor and lupus anticoagulant were checked in order to screen the patient for vasculitis and fibromuscular dysplasia, none of them showed significant results. The Pfizer-BioNTech COVID-19 vaccine that the patient had received a few days ago was the only plausible trigger. In conclusion, COVID-19 vaccination might lead to multiple cerebrovascular changes in a short period of time.

Immunogenic cell death as driver of autoimmunity in granulomatosis with polyangiitis.

Cell death and dysregulated clearance of dead cells play essential roles in the induction of chronic inflammatory processes and autoimmune diseases. Granulomatosis with polyangiitis (GPA), a neutrophil-driven autoimmune disorder, is characterized by necrotizing inflammation predominantly of the respiratory tract and an anti-neutrophil cytoplasmic autoantibody (ANCA)-associated systemic necrotizing vasculitis. Defective regulation of neutrophil homeostasis and cell death mechanisms have been demonstrated in GPA. Disturbed efferocytosis (i.e., phagocytosis of apoptotic neutrophils by macrophages) as well as cell death-related release of damage-associated molecular patterns (DAMP) such as high mobility group box 1 (HMGB1) contribute to chronic non-resolving inflammation in GPA. DAMP have been shown to induce innate as well as adaptive cellular responses thereby creating a prerequisite for the development of pathogenic autoimmunity. In this review, we discuss factors contributing to as well as the impact of regulated cell death (RCD) accompanied by DAMP-release as early drivers of the granulomatous tissue inflammation and autoimmune responses in GPA.

29-Year-Old Man With Acute Gastric Distention

29-Year-Old Man With Acute Gastric Distention

Eosinophilic granulomatosis with Anti-MPO-C-ANCA-associated polyangitis: a case report illustrating the diagnosis difficulty

Eosinophilic granulomatosis with polyangitis (EGPA), formerly known as Churg-Strauss syndrome, with antineutrophil cytoplasmic autoantibodies (ANCA) is a rare vasculitis. The CANCA is mainly antibodies to proteinase-3 and the P-ANCA is antibodies to myeloperoxidase (MPO). The EGPA with C-ANCA with antibodies anti-MPO has never been described in Subsaharan Africa. Medical investigations allowed excluding infectious diseases, malignancies and other rheumatic affections. Thus, clinical and paraclinical data suggested an atypic EGPA with MPO-C-ANCA. In our knoweledge, we reported here the first case of EGPA wtih MPO C-ANCA from Madagascar. The EGPA was succesfully controled with steroid treatment.

Relevance of Combined Clinicopathologic Phenotype and Antineutrophil Cytoplasmic Autoantibody Serotype in the Diagnosis of Antineutrophil Cytoplasmic Autoantibody Vasculitis

Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), 2 major clinicopathologic variants of antineutrophil cytoplasmic autoantibody (ANCA) vasculitides, are mostly associated with proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA, respectively. Less is known regarding the uncommon forms of ANCA vasculitis, PR3-ANCA MPA and MPO-ANCA GPA. In this cohort study we detailed the clinical presentation and outcome of patients with PR3-ANCA MPA and MPO-ANCA GPA from the Glomerular Disease Collaborative Network (GDCN) inception cohort. Baseline clinical manifestations, relapses, end-stage kidney disease (ESKD), and survival were compared within MPA cases by PR3-ANCA (n= 116) versus MPO-ANCA (n= 173) and within GPA cases by PR3-ANCA (n= 108) versus MPO-ANCA (n= 43). Fisher's exact test and Wilcoxon two sample test were used for comparisons. Proportional hazards models were used to evaluate the development of relapses, ESKD, and death. Patients with PR3-ANCA MPA were younger (53 years vs. 62 years, P= 0.0007) and had increased prevalence of joint involvement (56% vs. 40%, P= 0.0115) and ear, nose, and throat (ENT) involvement (44% vs. 26%, P= 0.002) than MPO-ANCA MPA. Relapses, ESKD, and survival were similar between both MPA subsets. Within the GPA group, patients with MPO-ANCA GPA were older (61 years vs. 46 years, P= 0.0007) and more likely female (56% vs. 35%, P= 0.027) than PR3-ANCA GPA patients. MPO-ANCA GPA was also characterized by less prevalent ENT manifestations (58% vs. 77%, P= 0.028) and neurologic manifestations (5% vs. 25%, P= 0.0029), and increased ESKD and mortality. PR3-ANCA MPA and MPO-ANCA GPA are clinicopathologically distinct subsets of ANCA vasculitis that differ from MPO-ANCA MPA and PR3-ANCA GPA. Although the impact of these differences on the clinical management and outcome warrants further evaluation, these results support the recommendation of including both the phenotypic diagnosis and ANCA serotype in the diagnosis of ANCA vasculitis.

Antineutrophil Cytoplasmic Autoantibodies-Associated Vasculitides and Risk of Stroke: A Systematic Review and Meta-analysis.

Increased incidence of cardiovascular disease, including stroke, has been consistently observed in patients with chronic inflammatory diseases, although data on antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are still limited due to the relative rarity of the disease. Two investigators independently searched published studies indexed in MEDLINE and EMBASE database from inception to June 2019 using the search terms related to AAV and stroke. The eligible study must be cohort study that consisted of cohort of patients with AAV and cohort of patients without AAV. The study must follow the participants for incident stroke. The magnitude of difference in the incidence of stoke between the cohorts must be reported. Pooled effect estimates were calculated by combining the effect estimate of each eligible study using generic inverse variance method. Statistical heterogeneity was assessed using the Cochran's Q test and I2 statistics. All analyses were conducted using RevMan 5.3 software from the Cochrane Collaboration. A total of six cohort studies fulfilled the eligibility criteria and were included into the meta-analysis. Patients with AAV had a higher risk of developing incident stroke than individuals without AAV with the a pooled risk ratio of 2.02 (95% CI, 1.02-4.00; I2 of 89%). Funnel revealed no suggestive evidence of publication bias. A significantly higher risk of incident stroke among patients with AAV than individuals without AAV was demonstrated by this meta-analysis.

Granulomatous vasculitides and vasculitides with extravascular granulomatosis

Vasculitides are inflammatory diseases of blood vessels caused by autoimmune or infectious processes, which are associated with alterations and destruction of the vascular wall. From ahistopathological point of view, granulomatous vasculitides can be distinguished from necrotizing vasculitides with respect to the pattern of inflammation. Granulomatous vasculitides are characterized by intramural, predominantly lymphohistiocytic infiltrates with the formation of giant cells. They include giant cell arteritis (GCA) and Takayasu arteritis (TAK). By contrast, anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) belongs to the group of necrotizing vasculitides. AAV includes granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA). In addition to systemic necrotizing small vessel vasculitis, GPA and EGPA are characterized by extravascular granulomatous necrotizing inflammation mainly affecting the upper and/or lower respiratory tract, in EGPA with eosinophilic infiltrates. These granulomatous lesions are part of the autoimmune process and associated with tissue damage.

C5a receptor antagonism coming of age for vascular pathology

The Food and Drug Administration recently approved the new drug avacopan for a relatively rare disease, anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. Avacopan is an antagonist of receptor-1 for anaphylatoxin C5a (C5aR1) that is the first one to meet all expectations of an orally bioavailable drug. Pharmacological effects of C5a on vascular tissue are reviewed; they are essentially indirect, via resident or infiltrating leukocytes, and largely mediated by vasoconstrictor prostanoids that are potentially thrombogenic. The in vivo acute neutropenic effect of C5a and various responses of isolated neutrophils to the peptide have been exploited in the preclinical development of avacopan, but not the prominent hemodynamic responses. Possible clinical risks and extension of therapeutic C5aR1 blockade are discussed. Therapeutic intervention on the blood-derived peptide C5a and on its G protein coupled receptor for specific forms of vascular injury contrasts with other current research approaches in vascular pathology, such as investigating the roles of cytokines and intracellular signaling.