Presence Of Antineutrophil Cytoplasmic Antibodies Research Articles

On the problem of differential diagnosis in the detection of antineutrophil cytoplasmic antibodies

Vasculitides associated with antineutrophil cytoplasmic antibodies (ANCA) are a group of systemic autoimmune diseases characterized by necrotizing lesions of the walls of predominantly small vessels and the presence of ANCA against proteinase 3 or myeloperoxidase. However, an increase in ANCA levels can also be observed in other diseases, including autoimmune, malignant and infectious diseases, which complicates the interpretation of clinical and laboratory data and requires a differential diagnosis.

Measurement of Neutrophil Extracellular Traps as a Biomarker for the Differential Diagnosis Between Antineutrophil Cytoplasmic Antibody-Positive Individuals With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis and Nonautoimmune Diseases.

Neutrophil extracellular traps (NETs) have a correlation with disease activity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, it is not known whether there is an association between NETs and the presence of ANCA in other diseases. This study aimed to assess the occurrence of NETs in individuals with ANCA and whether serum NET quantitation is capable of distinguishing them with regard to the diagnosis. This was a cross-sectional, observational study. From the positive ANCA by indirect immunofluorescence, 94 individuals were divided into groups: AAV, infectious diseases, and neoplastic diseases. Healthy controls served for comparisons. Neutrophil extracellular traps were evaluated through the investigation of NET remnants, by detecting cell-free DNA bound to proteins such as histone, myeloperoxidase, and neutrophil elastase (NE). In patients with perinuclear ANCA (p-ANCA) the detection of NETs by NE was able to distinguish AAV from infection/neoplasia and healthy controls. Receiver operating characteristic curves for serum NETs by NE in patients with p-ANCA were drawn in 2 situations: AAV versus infection/neoplasia, showing a sensitivity of 0.65 and specificity of 0.84, with an area under the curve of 65%; and AAV versus controls, showing a sensitivity of 0.84 and a specificity of 0.88, with an area under the curve of 96%. For p-ANCA-positive individuals, we found higher serum NETs detected by NE-DNA in those with chronic infectious and neoplastic diseases than in AAV individuals and healthy controls. This allows us to infer that the evaluation of serum NETs may be of value as a biomarker for differential diagnosis.

Nailfold videocapillaroscopy in antineutrophil cytoplasmic antibody-associated vasculitis.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of illnesses that cause inflammation and alterations to small vessels in the body. Some of the most common and detrimental manifestations, including alveolar hemorrhage and glomerulonephritis, are caused by this capillary inflammation. We sought to clarify whether patients with AAV would have abnormal nailfold capillaries when evaluated with nailfold videocapillaroscopy. Patients with a current diagnosis of AAV and a control group were identified for enrollment. Nailfold videocapillaroscopy images were used for a semiquantitative analysis on capillary density, morphology, dilation, and microhemorrhage after review by 2 rheumatologists. Disease characteristics, occurrence of recent disease flare, and presence of ANCA were recorded. Thirty-three patients with a diagnosis of AAV and 21 controls were recruited. The AAV group had a median age of 59 and 17 (52%) were women. Granulomatosis with polyangiitis was the most common diagnosis (19 [58%]), followed by eosinophilic granulomatosis with polyangiitis (7 [21%]) and microscopic polyangiitis (7 [21%]). Twenty-seven patients (82%) had positive ANCA tests. After assessment of capillary density, dilation, morphology, microhemorrhages, and disorganization, there were no statistically significant differences between the 2 groups. There was no evidence of differences in nailfold capillaroscopy abnormalities between those diagnosed with AAV and the control group. While this cohort was relatively small, we did not find a high enough prevalence or specific phenotype of capillary abnormalities that could aid in diagnosis or prognostication of these diseases in the clinical setting.

The role of ANCA in the management of cocaine-induced midline destructive lesions or ENT pseudo-granulomatosis with polyangiitis: a London multicentre case series.

In this multicentric study involving three London hospitals, we compared ANCA-positive and ANCA-negative cocaine-induced midline destructive lesions (CIMDL) patients to assess how presence of antineutrophil cytoplasmic antibodies (ANCA) may correlate with disease severity. Our secondary aims are to better classify etiology centered around ANCA positivity and, consequently, better disease management. A retrospective review was performed to identify patients with CIMDL seen between January 2019 and December 2022. Population data including age, sex, presentation, endoscopic findings, duration of cocaine use and active use of cocaine, type of treatment, laboratory (including ANCA serology), radiological, and histological findings were collected. Forty CIMDL patients (25 male, median age of 42 years) were identified. The majority of them (72.5%) presented with either a septal perforation, a saddle nose deformity (22.5%), and/or a palatal fistula (20.0%). ANCA was positive in 71.1% of cases (66.7% p-ANCA). No statistically significant differences in the general characteristics, type of treatment, laboratory results, radiological or histological findings were observed when comparing ANCA-positive and ANCA-negative CIMDL patients or when comparing p-ANCA and c-ANCA patients. Similarly, no statistically significant difference was obtained when comparing the pattern of distribution of lesions between the two groups. A large percentage of CIMDL patients showed positive ANCA test (71.1%) and in the majority of the cases a p-ANCA pattern specifically targeting PR3 (p-ANCA, PR3 + MPO-). However, ANCA positivity or presence of a specific ANCA pattern wasnot associated with more severe presentation or more aggressive disease. Given its similarities to granulomatosis with polyangiitis (GPA), we recommend the use of the term "cocaine-induced ENT pseudo-GPA" instead of CIMDL. IV Laryngoscope, 134:2609-2616, 2024.

Pneumorenal Syndrome Complicating ANCA-Negative Pauci-Immune Vasculitis Associated with Atypical Mycobacteriosis: Case Report

Among the forms of pneumorenal syndrome (PRS), one of the most urgent is characterized by the combination of diffuse alveolar hemorrhage and rapidly progressive glomerulonephritis (RPGN). In 90% of cases, it is the manifestation of an autoimmune disease, such as pauci-immune vasculitis with anti-neutrophil cytoplasmic antibodies (ANCA) or Goodpasture's disease with the presence of antibodies directed against the basement membrane of the glomerular and alveolar capillaries (anti-GBM). These antibodies are absent in approximately 10% of cases with histological confirmation in the context of rare clinical situations. We report a case of a 66-year-old patient, with a history of alcoholism and active smoking, who was admitted to the hospital for respiratory distress with hemoptysis. The admission assessment showed severe renal failure requiring hemodialysis upon admission. ANCA and anti-GBM, as well as all other autoantibodies were negative. A renal biopsy revealed pauci-immune extra-capillary glomerulonephritis with the majority of chronic lesions. The orientation of the diagnostic approach in search of other causes of pauci-immune vasculitis with negative antibodies has been initiated. He was treated with glucocorticoids in combination with cyclophosphamide. The initial evolution was marked by the improvement of respiratory symptoms and a less considerable recovery of renal function. PRS can develop without the presence of ANCA or other autoantibodies. The diagnosis is then made by histology. Renal damage, such as extra-capillary glomerulonephritis (GN), is more severe and has a very poor prognosis with a high risk of mortality. The absence of ANCA should never delay diagnosis and treatment.

Antineutrophil cytoplasmic antibody-associated vasculitis with systemic sclerosis: a fatal case report

Introduction and importance: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare co-occurrence with systemic sclerosis, in around 2.5–9% of patients. The clinical manifestations and prognosis of vasculitis in systemic sclerosis depend on organ involvement. It presented with rapidly progressive acute renal failure without malignant hypertension, and with pitting hand and foot ulcers get along with purpuric vasculitis in some cases reports. Reports had found that survival in those with pulmonary-renal syndrome is poor. However, high-dose corticosteroids and cyclophosphamide increase the survival percent in those patients. Case presentation: An 81-year-old female was admitted for newly diagnosed acute renal failure and highly elevated C-reactive protein levels. She was diagnosed with systemic sclerosis 8 years previously, with a 3-year history of interstitial lung disease, and a 2-year history of pulmonary hypertension. Treatment included home oxygen on demand, prednisone 5 mg/day, and azathioprine 75 mg daily. On physical examination, she had sclerodactyly, both extremities ulcers, severe livedo reticularis, and hyperpigmented papules on her hand and feet. Laboratory findings included a markedly positive MPO (p-ANCA), and anti-Scl-70. She was treated with pulse methylprednisolone without any improvement. After a day, she developed anuria and became comatose. Then, she developed cardiac arrest, leading to death. Clinical discussion: The presence of ANCA in systemic sclerosis patients ranges from 2.5 to 9% of systemic sclerosis patients. It presented with rapidly progressive acute renal failure without malignant hypertension, and with pitting hand and foot ulcers. The treatment with high-dose corticosteroids and cyclophosphamide is benefit. Survival in those with pulmonary-renal syndrome is poor. Conclusion: The presence of ANCA-associated vasculitis is rarely reported with scleroderma. It occurs most commonly in women with limited or Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia (CREST) variants of scleroderma, as well as those with overlap features. Severe manifestations including pulmonary-renal syndrome and death may occur.

New therapeutic approaches with biological drugs for eosinophilic granulomatosis with polyangiitis

Eosinophilic granulomatosis with polyangiitis (EGPA) is a multiorganic syndrome that affects the cardiovascular, neurologic, renal, and gastrointestinal systems with an incidence ranging from 0 case to 67 cases per one million person-years, and its pathophysiology remains unknown. It is believed that genetic factors, the environment, and changes in immune system function contribute to the development of EGPA, overlapping the immune mechanisms of vasculitides and the pathologic mechanisms in eosinophilic syndromes. This disease is commonly divided into two phenotypes depending on the presence of antineutrophil cytoplasmic antibodies (ANCA). ANCA-positive patients usually have more vasculitic manifestations like peripheral neuropathy, purpura, renal involvement, and biopsy-proven vasculitis. The keystone of EGPA therapy is systemic corticosteroids (CS) as monotherapy or in combination with other immunosuppressive treatments, and recently the efficacy of eosinophil-targeted biotherapy, anti-interleukin-5 (IL-5), has been shown to be efficacious in EGPA. Although this phenotype/phase distinction has not yet had an impact on the current treatment strategies, emerging targeted biotherapies under evaluation could lead to a phenotype-based approach and personalised treatment regimens for EGPA patients. The present review describes the new therapeutical approaches with biological drugs for EGPA.

Identification of proteinase 3 autoreactive CD4+T cells and their T-cell receptor repertoires in antineutrophil cytoplasmic antibody–associated vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease involving autoreactivity to proteinase 3 (PR3) as demonstrated by presence of ANCAs. While autoantibodies are screened for diagnosis, autoreactive T cells and their features are less well-studied. Here, we investigated PR3-specific CD4+T cell responses and features of autoreactive T cells in patients with PR3-AAV, using a cohort of 72 patients with either active or inactive disease. Autoreactive PR3-specific CD4+T cells producing interferon γ in response to protein stimulation were found to express the G-protein coupled receptor 56 (GPR56), a cell surface marker that distinguishes T cells with cytotoxic capacity. GPR56+CD4+T cells were significantly more prominent in the blood of patients with inactive as compared to active disease, suggesting that these cells were affected by immunosuppression and/or that they migrated from the circulation to sites of organ involvement. Indeed, GPR56+CD4+T cells were identified in T-cell infiltrates of affected kidneys and an association with immunosuppressive therapy was found. Moreover, distinct TCR gene segment usage and shared (public) T cell clones were found for the PR3-reactive TCRs. Shared T cell clones were found in different patients with AAV carrying the disease-associated HLA-DP allele, demonstrating convergence of the autoreactive T cell repertoire. Thus, we identified a CD4+T cell signature in blood and in affected kidneys that display PR3 autoreactivity and associates with T cell cytotoxicity. Our data provide a basis for novel rationales for both immune monitoring and future therapeutic intervention in PR3-AAV.

The effect of various forms of treatment of vasculitis on C3, C4 and C5a complement levels in infants and children attending Assiut University Children Hospital (AUCH)

Vasculitis is an umbrella term for various and heterogeneous disorders sharing the presence of inflammation of blood vessel walls (Geetha & Jefferson, 2020). Immune cell infiltrates involve the presence of leukocytes in the vessel with immune-complex deposition, which implies the activation of the complement system and then the swelling and destruction of vessel mural structures. The lumen is narrowed or occluded leading to ischemia and necrosis (Chimenti et al., 2015). It produces local symptoms resulting in hypoperfusion, infarction and hemorrhage and systemic symptoms with an increase in acute phase reactants (Salvador, 2020). According to the size of the blood vessel affected and the distribution of vascular injury, pediatric vasculitis is classified into small vessel vasculitis as in Henochonlein Purpura (HSP), medium-sized vessel vasculitis as in Kawasaki disease and large vessel vasculitides affecting the aorta and its proximal branches. Some forms of small vessel vasculitis are characterized by the presence of antineutrophil cytoplasmic antibodies (ANCAs), whereas others are associated with immune complex deposition in affected tissues. Clinical presentation supported by specific laboratory test, imaging, and confirmatory histology are necessary in order to perform vasculitides’ diagnosis (Sivaraman et al., 2020). To assess the severity of vasculitis and response to treatment, urinary biomarkers such as albumin/creatinine ratio (A/C ratio) in urine have been proved to be easily done and correlated well with both clinical and serological results (Zhang, 2020). Aim of Work: The aim of this study is to assess the effect of various forms of drugs, used in treatment of vasculitis, on the serum levels of complements (C3, C4, and C5a) and Antineutrophil cytoplasmic antibodies (ANCA), in infants and children attending Assiut University Children Hospital (AUCH). Conclusion: In conclusion, cases on combined Methotrexate and Steroid therapy scored best regarding the lowering of C5a level in serum, however, in our cases as a whole, the level of C5a didn’t differ significantly from its level in control. Although the 3 arms of therapy used in this study had good effect on C3 & C4 levels, yet their effect on C5a level was not significant from control. This finding could be explained by the fact that most of our studied cases were of the immune-complex deposition diseases type (which have no effect on C5a) and were ANCA negative. Therefore, C5a inhibitor drugs probably will not be suitable in treatment of most common causes of pediatric vasculitis encountered in this series. Perhaps, this type of therapy might be used in ANCA-Positive associated vasculitides, e.g. Wegener’s Granulomatosis. Further research with bigger number of ANCA positive cases is needed to decide whether such cases could benefit from the use of C5a inhibitors or not.

The Presence of Antineutrophil Cytoplasmic Antibodies and Antiphospholipid Antibodies in Patients with Severe Acute Respiratory Syndrome Coronavirus 2: A Case-Control Study among Sudanese Patients.

Patients infected with COVID-19 are at an increased risk for thrombosis, suggesting a possible role of COVID-19 in the induction of coagulopathy. This study aimed to investigate the presence of prothrombotic antineutrophil cytoplasmic antibodies (ANCA) and antiphospholipid antibodies (aPLs) in the course of COVID-19 infection and to correlate these markers with severity and fatality, suggesting that COVID-19-induced autoimmune thrombosis is a possible axis in the inflammatory circuit of this infection. To investigate this, we conducted a case-control study which included patients with a positive reverse transcription-polymerase chain reaction (RT-PCR) test of COVID-19 and a control group with negative COVID-19 PCR and antibody (IgG-IgM and IgA nucleoprotein) ELISA results. An indirect immunofluorescence assay using granulocyte biochips (Aesku slides from AESKU DIAGNOSTICS, Germany) was used to detect ANCA (IgG), as well as multiplex ELISA for the detection of antiphospholipid antibodies for all patients with COVID-19 and for the control group. The results revealed the detection of antiphospholipid antibodies (IgG) in one patient out of the 45 patients in the case group. 1/45(2.2%) and 7/45(15.6%) tested positive for ANCA. Five were men and two were females, with one case revealed to be positive for both aPL and ANCA. A cytoplasmic reaction on the eosinophil granulocytes was observed in 2 cases; both were positive for ANCA. Other markers (CRP, APTT, PT, INR, ESR, and neutrophil and lymphocyte counts) were included in the study, along with demographic data. No aPL or ANCA reactions were detected for any of the control groups. These findings suggest that aPL and ANCA may be induced during the course of inflammation in COVID-19 and possibly contribute to the disease's severity and mortality.

A Smartphone-Based Low-Cost Inverted Laser Fluorescence Microscope for Disease Diagnosis.

Fluorescence microscopy is an important tool for disease diagnosis, often requiring costly optical components, such as fluorescence filter cubes and high-power light sources. Due to its high cost, conventional fluorescence microscopy cannot be fully exploited in low-income settings. Smartphone-based fluorescence microscopy becomes an interesting low-cost alternative, but raises challenges in the optical system. We present the development of a low-cost inverted laser fluorescence microscope that uses a smartphone to visualize the fluorescence image of biological samples. Our fluorescence microscope uses a laser-based simplified optical filter system that provides analog optical filtering capabilities of a fluorescence filter cube. Firstly, we validated our inverted optical filtering by visualizing microbeads labeled with three different fluorescent compounds or fluorophores commonly used for disease diagnosis. Secondly, we validated the disease diagnosis capabilities by comparing the results of our device with those of a commercial fluorescence microscope. We successfully detected and visualized Trypanosoma cruzi parasites, responsible for the Chagas infectious disease and the presence of Antineutrophil cytoplasmic antibodies of the ANCA non-communicable autoimmune disease. The samples were labeled with the fluorescein isothiocyanate (FITC) fluorophore, one of the most commonly used fluorophores for disease diagnosis. Our device provides a 400× magnification and is at least one order of magnitude cheaper than conventional commercial fluorescence microscopes.

Expert Perspective: Management of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

The antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) comprise a major subset of diseases that cause destructive inflammation of small and medium-sized blood vessels. Although these conditions have a predilection for pulmonary and renal involvement, they are in fact protean diseases that can involve essentially any organ system. AAV is among the most difficult rheumatic diseases to diagnose and treat. Therapy for AAV has evolved over the past two decades. Rituximab, an anti-CD20 monoclonal antibody, is now the preferred agent for remission induction in conjunction with a reduced-dose glucocorticoid taper. Rituximab is also often a key therapy for remission maintenance. Glucocorticoid toxicity reduction has become a major priority for treatment regimens. Avacopan, an important new adjunct to remission induction therapy, may reduce glucocorticoid use and its resulting toxicity. The role of avacopan as a remission maintenance agent requires further study. The duration of immunosuppression following remission is guided by a number of factors, including the patient's overall clinical state, the degree of damage from previous disease activity, the tolerability of remission maintenance medications, and SARS-CoV-2 vaccination and immunity status. Certain features, including history of previous relapse, the presence of ANCA directed against proteinase 3, and a diagnosis of granulomatosis with polyangiitis, favor prolonged remission maintenance therapy. The interval between rituximab doses can usually be lengthened over time during the maintenance phase.

DNASE1L3 deficiency, new phenotypes, and evidence for a transient type I IFN signaling.

Deoxyribonuclease 1 like 3 (DNASE1L3) is a secreted enzyme that has been shown to digest the extracellular chromatin derived from apoptotic bodies, and DNASE1L3 pathogenic variants have been associated with a lupus phenotype. It is unclear whether interferon signaling is sustained in DNASE1L3 deficiency in humans. To explore interferon signaling in DNASE1L3 deficient patients. To depict the characteristic features of DNASE1L3 deficiencies in human. We identified, characterized, and analyzed five new patients carrying biallelic DNASE1L3 variations. Whole or targeted exome and/or Sanger sequencing was performed to detect pathogenic variations in five juvenile systemic erythematosus lupus (jSLE) patients. We measured interferon-stimulated gene (ISG) expression in all patients. We performed a systematic review of all published cases available from its first description in 2011 to March 24th 2022. We identified five new patients carrying biallelic DNASE1L3 pathogenic variations, including three previously unreported mutations. Contrary to canonical type I interferonopathies, we noticed a transient increase of ISGs in blood, which returned to normal with disease remission. Disease in one patient was characterized by lupus nephritis and skin lesions, while four others exhibited hypocomplementemic urticarial vasculitis syndrome. The fourth patient presented also with early-onset inflammatory bowel disease. Reviewing previous reports, we identified 35 additional patients with DNASE1L3 deficiency which was associated with a significant risk of lupus nephritis and a poor outcome together with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Lung lesions were reported in 6/35 patients. DNASE1L3 deficiencies are associated with a broad phenotype including frequently lupus nephritis and hypocomplementemic urticarial vasculitis with positive ANCA and rarely, alveolar hemorrhages and inflammatory bowel disease. This report shows that interferon production is transient contrary to anomalies of intracellular DNA sensing and signaling observed in Aicardi-Goutières syndrome or STING-associated vasculitis in infancy (SAVI).

Cannonball Pulmonary Opacities Disclosing a Granulomatosis With Polyangiitis (GPA) With C-Antimyeloperoxidase (C-Anti-MPO) Antineutrophil Cytoplasm Antibodies (ANCAs)

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis of medium- and small-caliber vessels associated with the presence of antineutrophil cytoplasm antibodies (ANCAs) and antibodies specific for proteinase 3 (anti-PR3). The interest of this case lies on the fact that these antibodies are directed against myeloperoxidase revealed by the presence of scattered multiple pulmonary nodules.We report a 65-year-old-female patient who presented with a productive cough with mucus sputum associated with a cephalea for six months. The chest x-ray showed multiple pulmonary nodules, first suggesting a neoplastic origin. The initial etiological assessment was non-contributory. A month later, the patient developed pulmonary condensations and ocular signs. The etiological assessment then found ANCA anti-myeloperoxidase (anti-MPO)-GPA. A good knowledge of the clinical and radiological signs of GPA is important to quickly guide the diagnosis that will condition the prognosis of this disease.

MO051: Single-Cell Transcriptomics of Lupus Nephritis with ANCA Positive

Abstract BACKGROUND AND AIMS Lupus nephritis (LN) is one of the most common complications of SLE that can lead to worsened kidney function or renal failure. Antineutrophil cytoplasmic antibodies (ANCA) are autoantibodies that are against antigens in the cytoplasm of neutrophils and monocytes and can lead to an autoimmune disease characterized by vascular necrotizing inflammation. The presence of ANCA in serum can also be found in SLE. Positive ANCA serology in patients with LN is associated with distinct histopathologic features on renal biopsy and seems to affect outcome of LN. Deeper understanding of the molecular pathogenesis in LN with ANCA positive is needed to identify novel targets improve the outcome of LN. METHOD Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from one LN patient with PR3-ANCA positive and a healthy adult kidney. We identified distinct cell clusters through unsupervised clustering analysis. Identification of the differentially expressed genes (DEGs) and enrichment analysis as well as the interaction between cells were also performed. RESULTS Unsupervised clustering analysis identified 15 distinct cell types including all of the renal intrinsic cells and major immune cells. The DEGs in kidney endothelial cells and intercalated cells were primarily enriched in genes involved in the regulation of inflammation and immune response including IL-17 signaling, TNF signaling, NOD-like receptor signaling and Th17 cell differentiation. Macrophages displayed increased expression of HLA-DRB5, which plays a central role in the immune system by presenting peptides derived from extracellular proteins. TYROBP, a gene plays a role in signal transduction and inflammation, was also high-expressed in macrophages from kidney of LN with PR3-ANCA positive. The receptor-ligand crosstalk analysis highlighted the interactions between endothelial cells and other cells in LN, which infers great importance in LN. CONCLUSION We provide a searchable resource of single-cell RNA sequencing to LN with PR3-ANCA positive to uncover intercellular interactions, elucidate key pathways underlying the pathogenesis and offer new insight into therapeutic targets of this unique type of LN.

MO218: Anca-Associated Vasculitis After SARS-COV-2 Vaccination in a Patient With HLA-DRB1*09: 01 ALLELE: A Case Report and Literature Review

Abstract BACKGROUND AND AIMS A Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), presents with severe pneumonia and fatal systemic complications. Currently, SARS-CoV-2 vaccines are effective in reducing the risk of onset and severity of the disease. However, autoimmune diseases, including anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), have been reported as rare complications of the COVID-19 vaccine. Although the mechanism of ANCA vasculitis remains unknown, the genetic background, environmental factors and infections are involved in the development of the disease. Genome-wide association studies have identified several AAV-related haplotypes, including the human leukocyte antigen (HLA)-DRB1*09: 01 allele. Here, we report a case of AAV with a risk HLA allele after SARS-CoV-2 vaccination (Pfizer-BioNTech) and a literature review. METHOD Case report: A 71-year-old woman visited a clinic complaining of fever (37.0–37.5ºC) and malaise, 1 week after receiving second dose of COVID-19 vaccine (Pfizer-BioNTech). Two months after her first dose, her serum creatinine (Cr) level had increased from 0.86 mg/dL to 1.2 mg/dL with high titer of MPO-ANCA (280 IU/mL, normal value <3.5 IU/mL). Urinary microscopy revealed a red blood cell count of 30–49/high power field and a urinary protein–creatinine ratio of 1.06 g/gCr. We diagnosed MPO-AAV with manifestations of renal involvement, general symptoms and the presence of ANCA, as a cause of renal progressive glomerulonephritis. A course of corticosteroids and intravenous cyclophosphamide was initiated. After treatment, her general symptoms and urinary abnormalities disappeared, and renal insufficiency was improved as well. Three months later, the MPO-ANCA titer decreased to 27.4 IU/mL. We examined a human leukocyte antigen (HLA) haplotype and her allele was HLA-DRB1*09:01, which is a known risk allele of MPO-ANCA-associated vasculitis. RESULTS Review: Until November 30, 2021, we searched PubMed, including the case report study and seven cases have been reported as de novo AAV after SARS-CoV-2 vaccination. The mean age of patients was 72.5 years (three women and four men). The onset of symptomatic symptoms, such as fever, headache and malaise, ranged from the day after the first dose to 2 weeks after the second dose; consequently, renal dysfunction was detected. In six patients (except for our case), histological findings showed pauci-immune crescentic glomerulonephritis. Most patients received initial induction immunosuppressive therapy, including corticosteroids and cyclophosphamide, followed by maintenance therapy. The renal involvement of six patients improved, but one patient with severe renal dysfunction developed end-stage renal disease. Information on HLA allele was not available in any case. CONCLUSION This is the first case report of de novo AAV after SARS-CoV-2 vaccination in a patient with AAV susceptible HLA-DRB1*09:01 allele.

Frequency of anti-neutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus

IntroductionSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Patients with SLE exhibit multiple serum autoantibodies, including anti-neutrophil cytoplasmic antibodies (ANCAs). There are two main techniques to detect ANCAs: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). In this study, an attempt was made to determine the frequency and clinical associations of ANCAs in patients with SLE. MethodsA cross-sectional study was conducted in a tertiary care hospital in Colombia that included 74 patients with SLE. The presence of ANCAs was assessed using IIF with ethanol-fixed slides, and ELISA was used to detect antibody specificities for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA. ResultsOf the 74 patients with SLE evaluated, 60 (81.1%) of them were ANCA-positive by IIF. By contrast, only one patient showed specificity for PR3-ANCA by ELISA. The relevance of ANCA positivity by IIF and clinical and serological features was significant for renal involvement (p=.0174), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p=.0308). ConclusionANCAs are common in the serum of patients with SLE, as detected by ethanol-fixed slides with IIF staining. However, detection of specificity to PR3 and/or MPO is rare, thus highlighting the importance of detecting these autoantibodies by different techniques.

Cardiovascular involvement in ANCA associated vasculitis

Antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) is a group of vasculitis disorders characterized by the presence of ANCA which comprise of three diseases; granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) which are characterized by necrotizing inflammation of small vessels. Although vascular manifestations are common in GPA cardiac involvement remains rare. The aim of this study is to describe cardiovascular manifestations in patients with AAV. A retrospective study was conducted between 2000 and 2020, including patients with AAV hospitalized at the department of internal medicine in Fattouma Bourguiba university hospital, Tunisia. A total of 20 patients satisfied the diagnosis of AAV. Seven patients (35%) had cardiovascular involvement comprising five cases of GPA, one case of EGPA, and one case of MPA. It was significantly more frequent among men ( P = 0.23). It was more prevalent among patients with EGPA (50%) than patients with GPA (31%). In six patients, cardiovascular manifestations were the first clinical signs of the disease. Deep vein thromboses were reported in 5 patients: 3 patients had lower limb thrombosis, 1 patient had a pulmonary embolism and 1 patient had cerebral venous thrombosis. Four patients (25%) developed cardiac complications including 2 cases of pericarditis, one case of myocarditis, and one case of acute coronary syndrome. c-ANCA with anti PR3 specificity was positive in 3 patients. Six patients were treated with a combination of corticosteroids and cyclophosphamide. One patient received intravenous immunoglobulin. Four patients achieved complete remission. Venous thromboembolism is common in AAV with an incidence of 12.4%, but cardiac manifestations are rare. Cardiac involvement appears to be more prevalent in patients diagnosed with EGPA as compared to GPA patients.

Challenges in the Diagnosis of a Case of Granulomatosis with Polyangeitis

Abstract Granulomatosis with polyangiitis is a multisystem disease characterized by a necrotizing granulomatous vasculitis, typically associated with the presence of anti-neutrophil cytoplasmic antibodies. The lung is the most common organ involved in comparison to other vasculitis, but in the case presented by us the onset is otorhinolaryngology field, with a multitude of symptoms and immunological tests are initially negative. Over time, immunological tests become positive, but all this leading to a delay in diagnosis by 4 years and of course to a delay in treatment. In this paper we emphasize the usefulness of biopsy for diagnosis and use of anti-neutrophil cytoplasmic antibodies to classify the disease.

Immune Cells Profiling in ANCA-Associated Vasculitis Patients-Relation to Disease Activity.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of necrotizing multiorgan autoimmune vasculitides that predominantly affect small blood vessels and are associated with the presence of ANCAs. The aim was to assess regulatory and effector cell populations accompanied by the suPAR biomarker level and link the so-defined immune state to the AAV disease activity. The research involved a multicomponent description of an immune state encompassing a range of B and T cell subsets such as transitional/regulatory B cells (CD19+CD24++CD38++), naïve B cells (CD19+CD24INTCD38INT), Th17 cells, T regulatory cells (CD4+CD25+FoxP3+) and cytotoxic CD4+CD28− cells by flow cytometry. The suPAR plasma level was measured by ELISA. The results indicate that AAV is associated with an increased suPAR plasma level and immune fingerprint characterized by an expansion of Th17 cells and T cells lacking the costimulatory molecule CD28, accompanied by a decrease of regulatory populations (Tregs and transitional B cells) and NK cells. Decreased numbers of regulatory T cells and transitional B cells were shown to be linked to activation of the AAV disease while the increased suPAR plasma level—to AAV-related deterioration of kidney function. The observed immune fingerprint might be a reflection of peripheral tolerance failure responsible for development and progression of ANCA-associated vasculitides.