Dynamically changing antineutrophil cytoplasmic antibodies in granulomatosis with polyangiitis:A case report

BACKGROUND Granulomatosis with polyangiitis(GPA)is one of the most prevalent forms of the antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis.The diagnosis of GPA depends on clinical presentation,serological evidence of a positive ANCA,and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation.Cytoplasmic ANCA(c-ANCA)is positive in 65%-75% of GPA patients,accompanied by proteinase 3(PR3),the main target antigen of c-ANCA,another 5% of GPA patients had negative ANCA.CASE SUMMARY The patient,a 52-year-old male,presented with unexplained nasal congestion,tinnitus,and hearing loss.After a duration of 4 months experiencing these symptoms,the patient subsequently developed fever and headache.The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis,and the ANCA results were negative.The anti-infective therapy proved to be ineffective,but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day.However,after continuous use of methylprednisolone tablets for 3 months,the patient experienced a recurrence of fever accompanied by right-sided migraine,positive c-ANCA and PR3,and increased total protein in cerebrospinal fluid.The and cyclophosphamide 0.8 g monthly,the patient experienced alleviation of fever and headache.Additionally,the ANCA levels became negative and there has been no recurrence.CONCLUSION For GPA patients with negative ANCA,there is a potential for early missed diagnosis.The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.

Significance of antineutrophil cytoplasmic antibody in adult patients with Henoch-Schnlein purpura presenting mainly with gastrointestinal symptoms

AIM： To test the clinical significance of antineutrophil cytoplasmic antibody （ANCA） in evaluation of adult Henoch-Schonlein purpura （HSP） patients presenting mainly with abdominal symptoms. METHODS： Twenty-eight consecutive HSP patients who presented predominantly with abdominal symptoms were enrolled in this study. Control subjects included 27 ageand sex-matched patients with peptic ulcer disease, colon cancer, acute gastroenteritis, irritable bowel syndrome and colonic polyps. ANCA was measured by indirect immunofluorescence （IIF） in all patients, and follow-up ELISA was performed in patients with positive IIF tests. RESULTS： ANCA was detected in 9 HSP patients by IIF （2 were positive for c-ANCA and 7 were positive for p-ANCA）. No ANCA was found in the control group. The sensitivity and specificity of a positive ANCA test （either c- or p-ANCA） were 32.1% and 100% respectively. Only one out of the 9 patients with positive ANCA by IIF had positive ANCA by ELISA and the antigen was myeloperoxidase （MPO）. The patients positive for ANCA had higher HSP clinical scores, and were more likely to have renal function impairment. Patients with late purpura development were also associated with more severe clinical manifestations. CONCLUSION： A positive ANCA test is associated with more severe symptoms in HSP. After inflammatory bowel disease is excluded, a positive ANCA test provides a clue to the diagnosis of HSP presenting predominantly with abdominal symptoms.

A subset of ulcerative colitis with positive proteinase-3 antineutrophil cytoplasmic antibody

A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were in effective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates thatulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients, with additional advantages of having no noticeable side-effects and less financial burden.

Systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis overlap syndrome in a 77-year-old man: A case report

BACKGROUND Systemic lupus erythematosus(SLE)and antineutrophil cytoplasmic antibodyassociated vasculitis(AAV)are classically thought to cause renal impairment and small vessel vasculitis with different pathophysiologies.Their overlap constitutes a rare rheumatologic disease.To date,only dozens of such cases with biopsyproven glomerulonephritis have been reported worldwide typically in women of childbearing age.Here,we present a unique clinical case due to its rarity and individualized treatment of a Chinese man in his eighth decade of life.CASE SUMMARY A 77-year-old man was admitted to several hospitals for shortness of breath and received nonspecific treatments over the past 3 years.As his symptoms were not completely relieved,he visited our hospital for further treatment.Laboratory examinations revealed kidney dysfunction,severe anaemia,hypocomplementemia,glomerular proteinuria,and microscopic haematuria.Antinuclear antibodies,as well as anti-dsDNA antibodies,were positive.Computed tomography of the chest showed right pleural effusion.Renal biopsy was performed,and histology suggested crescentic glomerulonephritis,pauci-immune type.After treatment with plasmapheresis,glucocorticoid,and cyclophosphamide,the disease was in remission,and the patient remained in a stable condition for over 3 years post-hospital discharge.CONCLUSION Due to its complexity and rarity,SLE and AAV overlap syndrome is easily misdiagnosed.An accurate diagnosis and treatment at the earliest stage may significantly improve the condition and reduce irreversible organ injury.

Antineutrophil cytoplasmic antibodies crescentic allograft glomerulonephritis after sofosbuvir therapy

Antineutrophil cytoplasmic antibodies(ANCA) are well known to be associated with several types of vasculitis, including pauci-immune crescentic glomerulonephritis, a form of rapid progressive glomerular nephritis(RPGN). ANCA vasculitis has also been reported after administration of propylthiouracil, hydralazine, cocaine(adulterated with levimasole), allopurinol, penicillamine and few other drugs. All previously reported cases of drug-associated ANCA glomerulonephritis were in native kidneys. Sofosbuvir is a new and effective drug for hepatitis C virus infection. Here, we report a case of ANCA vasculitis and RPGN following sofosbuvir administration in a kidney transplant recipient. It also represents the first case of drug-associated ANCA vasculitis in a transplanted kidney. Further drug monitoring is necessary to elucidate the degree of association and possible causal effect of sofosbuvir and perinuclear ANCA vasculitis.

Myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis with headache and kidney involvement at presentation and with arthralgia at relapse:A case report

BACKGROUND Patients with proteinase 3-antineutrophil cytoplasmic antibody associated vasculitis(AAV)experience different manifestations at the initial onset and relapse.However,such cases of different initial and relapse manifestations have not been reported in myeloperoxidase(MPO)-AAV patients.CASE SUMMARY A 52-year-old woman was admitted to our hospital because of headache.Laboratory findings indicated nephrotic range proteinuria and microscopic hematuria,serum creatinine of 243μmol/L,anti-MPO antibody titer of>400 RU/mL,and positive perinuclearantineutrophil cytoplasmic antibody.Renal biopsy showed pauci-immune crescentic glomerulonephritis.The cerebrospinal fluid examination and brain magnetic resonance imaging did not show any abnormality.Therefore,MPO-AAV was diagnosed.Corticosteroids,plasmapheresis,and cyclophosphamide as induction therapy and mycophenolate mofetil(MMF)as maintenance therapy were administered.The patient’s headache disappeared;serum creatinine returned to normal;complete remission of microscopic hematuria and proteinuria was observed.Anti-MPO antibody titer reached normal limits after immunosuppressive treatment.Twenty-five months after stopping the immunosuppressive treatment,the patient relapsed with arthralgia,without neurological or renal involvement.The patient’s arthralgia improved after treatment with prednisone and MMF.CONCLUSION We have reported a rare case of MPO-AAV who initially presented with headache and kidney involvement.However,relapse presented with only arthralgia,which was completely different from the initial manifestations.This case suggests that AAV relapse should be highly suspected in MPO-AAV patients after remission,when clinical manifestations at relapse are different from those at onset.Prednisone and MMF may provide a good choice for refractory arthralgia during relapse in MPO-AAV patients.

Olfactory dysfunction in antineutrophil cytoplasmic antibodyassociated vasculitides: A review of the literature

Olfactory dysfunction(OD)has been described in patients with antineutrophil cytoplasmic antibody-associated vasculitides(AAV),but the underlying mechanisms are not completely understood.The causes of altered smell function can generally be divided into conductive,sensorineural or others.To date no specific treatment is available for AAV-related OD and the efficacy of currently available options has not been explored.The aim of this review is to provide an overview of the causes that may lead to OD in patients with AAV.Current available treatments for OD and possible options in patients with AAV presenting with smell impairment are also mentioned.

Risk factors for renal outcomes in children with antineutrophil cytoplasmic antibody-associated vasculitis:a nationwide retrospective study in China

Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.

CLINICAL AND PATHOLOGICAL MANIFESTATI-ONS OF PATIENTS WITH ANTINEUTROPHIL CYTO-PLASMIC AUTOANTIBODIES DIRECTED AGA INST PROTEINASE 3 OR MYELOPEROXIDASE

To compare the clinical and pathological manifestations of patients with antineutrophil cytoplasmic autoantibodies (ANCA) directed against proteinas e 3 (anti PR3) or myeloperoxidase (anti MPO). Methods. One hundred and forty patients with ANCA were detected for anti PR3 a nd anti MPO by ELISA. The clinical features at presentation, histopathological characteristics and outcome of all patients who were tested positive for anti P R3 or anti MPO were analysed.Results. In anti PR3 group (n=21), 16 cases (76.2%) had systemic vasculitis , in which Wegener’s granulomatosis prevailed (13 cases, 61.9%). In anti MPO g roup (n=31), 19 cases (61.3%) were diagnosed as systemic vasculitis and 12 case s (38.7%) as microscopic angiitis. For vasculitic patients with anti PR3 and a nti MPO, the disease duration at diagnosis was 9.6±2.0m and 4.4±0.9m respecti vely, P< 0.05;vasculitis activity index (BVAS) and mean number of affected organ were 22.5±2.1, 5.0±0.4 and 25.1±1.7, 4.8±0.4 respectively, P >0.05;upper r espiratory tract, eye and joint involvements were 11(68.8%), 7(43.8%), 11(68.8 %) and 7(36.8%), 2(10.5%), 5(26.3%) respectively, P< 0.05.Although there was no statistical difference in renal involvement between these two groups, patien ts with serum creatine >500 μmol/L were more commonly seen in anti MPO group t han in anti PR3 group, which were 8(42.1%) and 2(12.5%) respectively, P< 0.05 . Ten relapses were seen in anti PR3 group and only 2 in anti MPO group, but t he acute mortality rate in anti MPO group (5/19, 27.4%) was much higher than t hat in anti PR3 group (1/16, 6.3%). Conclusions. Anti PR3 and anti MPO occurred mainly in systemic vasculitis. A large divergence was seen in the disease spectrum between patients with anti PR 3 and those with anti MPO. In particular, upper respiratory tract, eye and join t involvements, granuloma formation and relapse were more prominent in anti PR3 patients. By contrast, the anti MPO patients had a more acute disease onset, m ore rapid progressive renal involvement and a higher acute mortality rate.

rare type of pancreatitis as the first presentation ofanti-neutrophil cytoplasmic antibody-related vasculitis

A pancreatic tumor was suspected on the abdominal ultrasound of a 72-year-old man. Abdominal computed tomography showed pancreatic enlargement as well as a diffuse, poorly enhanced area in the pancreas; endoscopic ultrasound-guided fine needle aspiration biopsy and endoscopic retrograde cholangiopancreatography failed to provide a definitive diagnosis. Based on the trend of improvement of the pancreatic enlargement, the treatment plan involved follow-up examinations. Later, he was hospitalized with an alveolar hemorrhage and rapidly progressive glomerulonephritis; he tested positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody(ANCA) and was diagnosed with ANCArelated vasculitis, specifically microscopic polyangiitis. It appears that factors such as thrombus formation caused by the vasculitis in the early stages of ANCArelated vasculitis cause abnormal distribution of the pancreatic blood flow, resulting in non-uniform pancreatitis. Pancreatic lesions in ANCA-related vasculitis are very rare. Only a few cases have been reported previously. Therefore, we report our case and a review of the literature.

Animal models for anti-neutrophil cytoplasmic antibody-associated vasculitis:Are current models good enough?

Antineutrophil cytoplasmic autoantibody(ANCA)-associated vasculitis(AAV)is a rare and severe systemic autoimmune disease characterized by pauci-immune necrotizing inflammation of small blood vessels.AAV involves multiple organ systems throughout the body.Our knowledge of the pathogenesis of AAV has increased considerably in recent years,involving cellular,molecular and genetic factors.Because of the controlled environment with no other confounding factors,animal models are beneficial for studying the mechanistic details of disease development and for providing novel therapeutic targets with fewer toxic side effects.However,the complexity and heterogeneity of AAV make it very difficult to establish a single animal model that can fully represent the entire clinical spectrum found in patients.The aim of this review is to overview the current status of animal models for AAV,outline the pros and cons of methods,and propose potential directions for future research.

Utility of serological markers in inflammatory bowel diseases: Gadget or magic?

The panel of serologic markers for inflammatory bowel diseases （IBD） is rapidly expanding. Although antiSaccharornyces cerev/siae antibodies （ASCA） and atypical perinuclear antineutrophil cytoplasmic antibodies （P-ANCA） remain the most widely investigated, an increasing amount of experimental data is available on newly discovered antibodies directed against various microbial antigens. The role of the assessment of various antibodies in the current IBD diagnostic algorithm is often questionable due to their limited sensitivity. In contrast, the association of serologic markers with disease behavior and phenotype is becoming increasingly well-established. An increasing number of observations confirms that patients with Crohn＇s disease expressing multiple serologic markers at high titers are more likely to have complicated small bowel disease （e.g. stricture and/or perforation） and are at higher risk for surgery than those without, or with low titers of antibodies. Creating homogenous disease sub-groups based on serologic response may help develop more standardized therapeutic approaches and may help in a better understanding of the pathomechanism of IBD. Further prospective clinical studies are needed to establish the clinical role of serologic tests in IBD.

Seroreactivity against Saccharomyces cerevisiae in patients with Crohn's disease and celiac disease

AIM:To explore whether there was anti-Saccharomyces cerevisiae antibodies (ASCA) positivity in our patients with biopsy-confirmed celiac disease. METHODS:A cohort of patients with inflammatory bowel diseases (42 patients with Crohn's disease and 10 patients with ulcerative colitis) and gluten sensitive enteropathy (16 patients) from Debrecen,Hungary were enrolled in the study. The diagnosis was made using the formally accepted criteria. Perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA), antiendomysium antibodies (EMA),antigliadin antibodies (AGA) and anti human tissue transglutaminase antibodies (tTGA) were investigated. RESULTS:The results showed that ASCA positivity occurred not only in Crohn's disease but also in Celiac disease and in these cases both the IgG and IgA type antibodies were proved. CONCLUSION:It is conceivable that ASCA positivity correlates with the (auto-) immune inflammation of small intestines and it is a specific marker of Crohn's disease.

Cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis:A case report

BACKGROUND Although cyclophosphamide(CPA)is the key drug for the treatment of autoimmune diseases including vasculitides,it has some well-known adverse effects,such as myelosuppression,hemorrhagic cystitis,infertility,and infection.However,CPA-associated severe enteritis is a rare adverse effect,and only one case with a lethal clinical course has been reported.Therefore,the appropriate management of patients with CPA-associated severe enteritis is unclear.CASE SUMMARY We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear,lung,and,kidney with positive myeloperoxidase-antineutrophil cytoplasmic antibody.She received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/mo.Ten days after the second course of intravenous CPA,she developed nausea,vomiting,and diarrhea,and was admitted to the hospital.Laboratory testing revealed hypoalbuminemia,suggesting proteinlosing enteropathy.Computed tomography revealed wall thickening of the stomach,small intestine,and colon with contrast enhancement on the lumen side.Antibiotics and immunosuppressive therapy were not effective,and the patient’s enteritis did not improve for>4 mo.Because her condition became seriously exhausted,corticosteroids were tapered and supportive therapies including intravenous hyperalimentation,replenishment of albumin and gamma globulin,plasma exchange,and infection control were continued.These supportive therapies improved her condition,and her enteritis gradually regressed.She was finally discharged 7 mo later.CONCLUSION Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.

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

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

Oral cyclophosphamide-induced posterior reversible encephalopathy syndrome in a patient with ANCA-associated vasculitis:A case report

BACKGROUND Posterior reversible encephalopathy syndrome(PRES)manifests many neurological symptoms with typical features on neuroimaging studies and has various risk factors.Cyclophosphamide is one of the therapeutic agents for antineutrophil cytoplasmic antibody(ANCA)-associated vasculitis.Cyclophosphamide as the sole cause of PRES has been reported in only a few cases.Herein,we report a unique case of early-onset oral cyclophosphamide-induced PRES in a patient with ANCA-associated vasculitis.CASE SUMMARY A 73-year-old man was transferred to our hospital for sepsis due to acute cholangitis.He had already received hemodialysis for two weeks due to septic acute kidney injury.His azotemia was not improved after sepsis resolved and perinuclear-ANCA was positive.Kidney biopsy showed crescentic glomerulonephritis.Alveolar hemorrhage was observed on bronchoscopy.He was initially treated with intravenous methylprednisolone and plasma exchange for one week.And then,two days after adding oral cyclophosphamide,the patient developed generalized tonic-clonic seizures.We diagnosed PRES by Brain magnetic resonance imaging(MRI)and electroencephalography.Seizures were controlled with fosphenytoin 750 mg.Cyclophosphamide was suspected to be the cause of PRES and withdrawal.His mentality was recovered after seven days and brain MRI showed normal state after two weeks.CONCLUSION The present case shows the possibility of PRES induction due to short-term use of oral cyclophosphamide therapy.Physicians should carefully monitor neurologic symptoms after oral cyclophosphamide administration in elderly patients with underlying diseases like sepsis,renal failure and ANCA-associated vasculitis.

Successful treatment of granulomatosis with polyangiitis using tocilizumab combined with glucocorticoids:A case report

BACKGROUND Tocilizumab is a humanized monoclonal antibody against the interleukin-6(IL-6)receptor that is commonly used to treat large vessel vasculitis and antineutrophil cytoplasmic antibody-related small vessel vasculitis.However,tocilizumab in combination with glucocorticoids for successfully treating granulomatosis with polyangiitis(GPA)has rarely been reported.CASE SUMMARY Here,we report a 40-year-old male patient who suffered GPA for 4 years.He was treated with multiple rounds of drugs,including cyclophosphamide,Tripterygium wilfordii,mycophenolate mofetil,and belimumab,with no improvement.In addition,he exhibited persistently high IL-6 levels.After tocilizumab treatment,his symptoms improved,and his inflammatory marker levels returned to normal.CONCLUSION Tocilizumab may be effective for treating GPA.

The role of high mobility group box 1(HMGB1)in the pathogenesis of kidney diseases

High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Prognosis of microscopic polyangiitis with renal involvement:report of 60 Chinese patients

With the widespread clinical application of renal biopsy and serum antineutrophil cytoplasmicantibody （ANCA） testing, the percentage of renal injuries caused by systemic small vessel vasculitis （ SVV ） including microscopic polyangiitis （ MPA ） and Wegener＇ s granulomatosis （WG） is on the rise in China. According to our previous report, SVV constituted 1.09% of diagnoses from all renal biopsies （5. 8% in secondary nephritis） and 14.4% of that from renal biopsies from patients with chronic renal failure,

Neutrophil Extracellular Traps in Autoimmune Diseases

INTRODUCTIONIn 2004, NETosis was first reported as an important step to kill bacteria by neutrophils. During the process ofN ETosis, neutrophil extracellular traps （NETs） that contain large web-like structures of decondensed chromatin decorated with histones and intracellular components, including neutrophil elastase （NE）, myeloperoxidase （MPO）, high mobility group protein B I （HMGBI）, and proteinase 3 （PR3）, are extruded into the extracellular space, The structures of NETs enable the neutrophil to potently catch and kill pathogens at the site of inflammation. Furthermore, increasing studies have identified the presence of NETs in autoimmune diseases. NETs deliver multiple autoantigens to host immtme system that induce autoimmune responses and directly release damage-associated molecular patterns to amplify inflammatory responses. Therefore, NETs are commonly described to play a crucial role in the pathogenesis and development of autoimmune diseases in recent years.