分子伴侣性自噬参与LAMP-2抗体诱导中性粒细胞胞外捕网形成

目的探讨分子伴侣性自噬在LAMP-2抗体诱导中性粒细胞胞外捕网(NETs)形成的作用及机制。方法采用PolymorphprepTM方法分离健康志愿者和抗中性粒细胞胞浆抗体相关性血管炎(AAV)患者外周静脉血中的中性粒细胞,直接离体或LAMP-2抗体刺激健康人外周血中性粒细胞,通过自噬阻断剂3-甲基腺嘌呤(3-MA)和放线菌酮(CHX)进行干预,免疫荧光观测NETs的形成,免疫荧光法和免疫印迹法检测分子伴侣自噬相关蛋白LAMP-2A、Hsc70的表达。结果与正常中性粒细胞组相比,AAV患者中性粒细胞LAMP-2A表达增加(P=0.002 3);LAMP-2抗体可诱导中性粒细胞LAMP-2A、Hsc70蛋白表达明显上调(P<0.01),CHX能明显降低LAMP-2抗体引起的LAMP-2A、Hsc70蛋白表达(P<0.000 1);与3-MA组相比,CHX组能明显减少LAMP-2抗体诱导的NETs形成(P<0.000 1)。结论 LAMP-2抗体可诱导人中性粒细胞分子伴侣性自噬增强及NETs形成,放线菌酮可抑制此过程,提示分子伴侣性自噬可能参与了NETs的形成。     

溶酶体膜蛋白-2抗体诱导中性粒细胞胞外捕网形成的实验研究

目的研究溶酶体膜蛋白-2抗体(LAMP-2-antibody)诱导中性粒细胞胞外捕网形成(NETosis)的作用,为进一步探讨这种新型细胞死亡模式在系统性小血管炎中的作用及机制奠定基础。方法采用PolymorphprepTM进行密度梯度离心法分离健康志愿者外周静脉血中性粒细胞,抗LAMP-2抗体刺激中性粒细胞,以及通过NADPH氧化酶抑制剂二甲苯基碘(DPI)阻断活性氧簇的产生,电镜、免疫荧光观测胞外捕网的形成,激光共聚焦检测自身抗原LAMP-2、PR3、MPO的表达。结果 LAMP-2抗体促进中性粒细胞胞外捕网NETs形成,自身抗原MPO、PR3及LAMP-2包含在NETs内,抑制NADPH氧化酶的活性可以阻断NETs形成。结论 LAMP-2抗体可能通过诱导中性粒细胞异常死亡,释放内源性危险信号,激活自身免疫反应等来维持血管炎的恶性持续状态。     

NETs 刺激下慢性支气管炎大鼠血清ANCA 产生机制探讨

目的:探讨长期慢性感染刺激诱导机体产生抗中性粒细胞胞浆抗体(ANCA)的机制。方法:烟熏法联合脂多糖气管内注入,建立慢性支气管炎大鼠模型,用佛波脂(PMA)体外刺激大鼠中性粒细胞产生中性粒细胞胞外网络(NETs),以NETs 免疫慢性支气管炎大鼠,比较慢性支气管炎NETs 刺激组(CB/ NETs)、慢性支气管炎组(CB)和正常组三组大鼠血清髓过氧化物酶鄄抗中性粒细胞胞浆抗体(MPO-ANCA)、血清瓜氨酸化的组蛋白H3(CitH3)、血清IFN-α水平及血清肌酐、血清尿素氮、尿红细胞计数、24 h 尿蛋白定量水平。结果:(1)CB/ NETs 组的血清MPO-ANCA 水平明显高于CB 组及正常组,(62.497 5±19.637 64)ng/ ml vs(17.380 6±4.886 49)ng/ ml,(20.888 4±4.396 07)ng/ ml(P<0.01)。(2)CB/ NETs 组的血清CitH3 水平明显高于CB 组及正常组,(32.597 4±20.291 5)ng/ ml vs (8.856 8±2.366 92)ng/ ml,(5.622 5±0.837 38)ng/ ml,(P<0.05,P<0.01)。(3)CB/ NETs 组中有两只大鼠的血清IFN-α水平异常升高(3 735.7、3 428.4 pg/ ml)。(4)三组大鼠的肾脏相关指标差异暂未呈现出统计学意义。(5)大鼠血清CitH3 水平与血清MPO-ANCA 水平呈正相关(r =0.61,P<0.05)。结论:慢性支气管炎长期、反复感染可导致ANCA 水平升高,从形成高水平的ANCA 到最终形成ANCA 相关性小血管炎尚需要时间。     

297例血管炎及自身免疫病患者抗中性粒细胞胞质抗体的分析

抗中性粒细胞胞质抗体（antineutropil cytoplasmic andbodis，ANCA）代表一族抗中性粒细胞胞质成分的抗体谱，是一种以中性粒细胞和单核细胞胞质成分为靶抗原的自身抗体，是十几年来发展起来的一种用于系统性小血管炎的特异性血清学诊断指标。我们将297例血管炎及自身免疫病患者检测ANCA的结果现报道如下。     

白蛋白对脂多糖诱导中性粒细胞胞外诱捕网生成的抑制作用

目的探讨白蛋白对脂多糖(LPS)诱导人外周血中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)生成的抑制作用及机制。方法分离人外周血中性粒细胞,分别培养于无白蛋白和含生理浓度白蛋白的培养体系中,加入LPS刺激,同时使用钙离子(Ca~(2+))以及自噬调节剂干预,采用sytox green染色法检测NETs,采用Fluo-4 AM染色法检测胞内Ca~(2+)水平,免疫荧光法检测NETs相关蛋白髓过氧化物酶(MPO)、弹性蛋白酶(NE)和瓜氨酸化组蛋白H3(cit-H3)以及自噬体相关蛋白LC3B的表达。结果 LPS可诱导中性粒细胞释放NETs,白蛋白可抑制NETs生成;白蛋白可降低LPS刺激下中性粒细胞胞内Ca~(2+)浓度和自噬水平。Ca~(2+)载体可增强中性粒细胞自噬水平并促进LPS诱导的NETs生成,Ca~(2+)螯合剂可降低自噬水平并抑制NETs生成。自噬激动剂可显著增强NETs,自噬抑制剂则显著抑制NETs。结论白蛋白对LPS诱导中性粒细胞胞外诱捕网(NETs)生成具有抑制作用,其作用机制可能与减少中性粒细胞Ca~(2+)内流进而抑制自噬有关。     

T细胞亚群与ANCA相关性小血管炎研究进展

抗中性粒细胞胞浆抗体(ANCA)相关性小血管炎(AAV)是一种以全身多系统小血管炎症和纤维素样坏死为主要特征的自身免疫性疾病。ANCA作为自身抗体,分别针对蛋白酶-3(PR3)和髓过氧化物酶(MPO)两种靶抗原在AAV过程中起重要作用。T细胞亚群与ANCA有较多参与和相互作用,也是AAV的关键致病因子,但其作用的具体机制尚不完全清楚。本文综述部分T细胞亚群与AAV的研究进展。     

丙基硫氧嘧啶引起抗中性粒细胞胞质抗体相关小血管炎并非药物性狼疮

目的 检测药物性狼疮（DIL）的血清学标志抗组蛋白抗体在抗中性粒细胞胞质抗体（ANCA）阳性的甲亢患者中的阳性率,并探讨丙基硫氧嘧啶（PITU）引起的ANCA相关小血管炎与DIL的关系。方法 以34例ANCA阳性的原发甲亢患者为研究对象,其中18例确诊为PITU引起的ANCA相关小血管炎;同时选取10例原发性ANCA相关小血管炎患者及10例初发未治疗的甲亢患者为对照,应用ELISA法检测抗组蛋白抗体。将我院确诊的PITU引起的ANCA相关小血管炎患者的临床资料与文献中抗甲状腺药物引起的DIL相比较。结果 所有原发性ANCA相关小血管炎的患者及初发未治疗的甲亢患者均未检测到抗组蛋白抗体;在34例PITU引起的ANCA阳性患者中仅1例（2．9％）抗组蛋白抗体阳性,此例患者为18例有血管炎临床表现中的1例（5．6％）。PITU引起的ANCA相关小血管炎不同于DIL,寡免疫复合物的坏死性新月体性肾炎及肺出血为前者的特征性表现。结论 PITU引起的ANCA相关小血管炎患者中抗组蛋白抗体的低发生率提示其与DIL可能不完全相同。     

肺炎链球菌诱导中性粒细胞胞外捕获网形成

目的初步探究肺炎链球菌诱导中性粒细胞胞外捕获网(NETs)形成的作用及调节机制,为进一步研究奠定基础。方法采用免疫磁珠法分选C57BL/6小鼠骨髓中性粒细胞,肺炎链球菌刺激中性粒细胞,分别采用脱氧核糖核酸酶(DNase)降解NETs和NADPH氧化酶抑制剂二苯基氯化碘盐(DPI)预处理中性粒细胞阻断活性氧簇(ROS)生成,免疫荧光染色观察NETs结构,检测游离DNA定量观察NETs的生成。结果肺炎链球菌刺激中性粒细胞释放NETs,DNase降解NETs结构,阻断ROS生成后NETs形成受抑。结论肺炎链球菌能够诱导NETs形成,DNase直接降解NETs或DPI抑制NETs形成可以成为调节NETs生成的有效途径。     

中性粒细胞胞外诱捕网在肺部疾病中作用的研究进展

中性粒细胞是肺部的常驻免疫细胞，受到刺激后，可释放含有中性粒细胞弹性蛋白酶、髓过氧化物酶、瓜氨酸组蛋白、细胞骨架蛋白的解凝染色质，即中性粒细胞胞外诱捕网(NETs)。NETs在肺部疾病中发挥抗感染作用，但过量的NETs释放也会导致肺部组织损伤、炎性反应增强和促进肿瘤转移。本文简要总结NETs的相关研究进展，为研发治疗肺部疾病的潜在药物提供新的思路。     

原发性小血管炎中ANCA IgG亚型的分布及临床意义

抗中性粒细胞胞浆抗体 (antineutrophilcytoplas micantibody ,ANCA)是一种以中性粒细胞和单核细胞胞浆成分为靶抗原的自身抗体 ,主要为IgG型。通过间接免疫荧光法可将ANCA分为两型 :胞浆型AN CA(cytoplasmicANCA ,c ANCA)与环核型ANCA (peri nuclearANCA ,p ANCA) 〔1〕 。到目前为止 ,已有多种中性粒细胞胞浆成分被证实为ANCA的靶抗原 ,其中最为重要的是髓过氧化物酶 (myeloperoxidase ,MPO)和蛋白酶 3(proteinase 3,PR3)。ANCA可在许多原发性小血管炎患者的血清中检测到 ,如韦格纳肉芽肿(Wegener′sgranulomatosis ,…     

Long pentraxin 3 (PTX3) expression and release by neutrophils in vitro and in ulcerative colitis

Pentraxin 3 (PTX3) is the first identified long pentraxin, and it is rapidly produced and released by several cell types in response to proinflammatory signals. The aim of this study was to investigate the behavior of neutrophils to produce PTX3 protein in response to proinflammatory cytokine IL-8 in vitro, as well as identify the expression pattern of PTX3 in human ulcerative colitis lesions. Pentraxin 3 protein was found to be present following release upon IL-8 stimulation in cultured neutrophils together with lactoferrin(+)-specific granules localized in neutrophil extracellular traps (NETs) formed by extruded DNA. Neutrophils in colonic mucosal tissue of patients with ulcerative colitis were the main cellular source of PTX3 protein, the expression of which is correlated well with the histological grades of inflammation. Immunofluorescence analysis against anti-lactoferrin antibody revealed the formation of NETs released from neutrophils within crypt abscess lesions, which were found to be activated through the expression of IL-8 receptor B (CXCR2). Of interest, neutrophils depleted of PTX3 protein were displayed, supporting the release of PTX3 from neutrophils in crypt abscess. We suspected that PTX3 protein may contribute to cell-mediated immune defense in inflamed colon tissue, and in particular in crypt abscess lesions, of patients with ulcerative colitis.     

Neutrophils activate plasmacytoid dendritic cells by releasing self-DNA-peptide complexes in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a severe and incurable autoimmune disease characterized by chronic activation of plasmacytoid dendritic cells (pDCs) and production of autoantibodies against nuclear self-antigens by hyperreactive B cells. Neutrophils are also implicated in disease pathogenesis; however, the mechanisms involved are unknown. Here, we identified in the sera of SLE patients immunogenic complexes composed of neutrophil-derived antimicrobial peptides and self-DNA. These complexes were produced by activated neutrophils in the form of web-like structures known as neutrophil extracellular traps (NETs) and efficiently triggered innate pDC activation via Toll-like receptor 9 (TLR9). SLE patients were found to develop autoantibodies to both the self-DNA and antimicrobial peptides in NETs, indicating that these complexes could also serve as autoantigens to trigger B cell activation. Circulating neutrophils from SLE patients released more NETs than those from healthy donors; this was further stimulated by the antimicrobial autoantibodies, suggesting a mechanism for the chronic release of immunogenic complexes in SLE. Our data establish a link between neutrophils, pDC activation, and autoimmunity in SLE, providing new potential targets for the treatment of this devastating disease.     

Neutrophil extracellular trap formation is associated with autophagy‐related signalling in ANCA‐associated vasculitis

Increasing evidence indicates that aberrant neutrophil extracellular trap (NET) formation could contribute to the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV). Recent research has provided evidence that a novel type of ANCA autoantibody, anti‐lysosomal membrane protein‐2 (LAMP‐2) antibody, may have a pathogenic role in AAV. We have shown previously that anti‐LAMP‐2 antibody‐stimulated NET formation contains autoantigens and anti‐microbial peptides. The current study sought to determine whether LAMP‐2, as a novel antigen of ANCA, was present on NETs in AAV patients, the influence of the anti‐LAMP‐2 antibody on the neutrophil apoptosis rate and the role of autophagy in anti‐LAMP‐2 antibody‐induced NET formation. NET formation was assessed using immunofluorescence microscopy, scanning electron microscopy or live cell imaging. The neutrophil apoptosis rate was analysed using fluorescence activated cell sorting (FACS). Autophagy was detected using LC3B accumulation and transmission electron microscopy. The results showed that enhanced NET formation, which contains LAMP‐2, was observed in kidney biopsies and neutrophils from AAV patients. The apoptosis rate decreased significantly in human neutrophils stimulated with anti‐LAMP‐2 antibody, and this effect was attenuated by the inhibitors of autophagy 3‐methyladenine (3MA) and 2‐morpholin‐4‐yl‐8‐phenylchromen‐4‐one (LY294002). The anti‐LAMP‐2 antibody‐stimulated NET formation was unaffected by benzyloxycarbonyl‐Val‐ Ala‐Asp (OMe)‐fluoromethylketone (zVAD‐fmk) and necrostatin‐1 (Nec‐1), which are inhibitors of apoptosis and necrosis, respectively, but was inhibited by 3MA and LY294002. Moreover, the proportion of LC3BI that was converted to LC3BII increased significantly (P = 0·0057), and massive vacuolizations that exhibited characteristics typical of autophagy were detected in neutrophils stimulated with anti‐LAMP‐2 antibody. Our results provide further evidence that autophagy is involved in ANCA‐induced NET formation in human neutrophils.     

IL-17A expressed on neutrophil extracellular traps promotes mesenchymal stem cell differentiation toward bone-forming cells in ankylosing spondylitis

Ankylosing spondylitis (AS) is an inflammatory disease characterized by excessive bone formation. We investigated the presence of neutrophil extracellular traps (NETs) in AS and how they are involved in the osteogenic capacity of bone marrow mesenchymal stem cells (MSCs) through interleukin-17A (IL-17A). Peripheral neutrophils and sera were obtained from patients with active AS and healthy controls. NET formation and neutrophil/NET-associated proteins were studied using immunofluorescence, immunoblotting, qPCR, and ELISA. In vitro co-culture systems of AS NET structures and MSCs isolated from controls were deployed to examine the role of NETs in the differentiation of MSCs toward osteogenic cells. Analysis was performed using specific staining and qPCR. Neutrophils from patients with AS were characterized by enhanced formation of NETs carrying bioactive IL-17A and IL-1β. IL-17A-enriched AS NETs mediated the differentiation of MSCs toward bone-forming cells. The neutrophil expression of IL-17A was positively regulated by IL-1β. Blocking IL-1β signaling on neutrophils with anakinra or dismantling NETs using DNase-I disrupted osteogenesis driven by IL-17A-bearing NETs. These findings propose a novel role of neutrophils in AS-related inflammation, linking IL-17A-decorated NETs with the differentiation of MSCs toward bone-forming cells. Moreover, IL-1β triggers the expression of IL-17A on NETs offering an additional therapeutic target in AS.     

Neutrophil extracellular traps can activate alternative complement pathways

The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative complement pathway on NETs in vitro was assessed by immunostain and confocal microscopy. Complement deposition on NETs were detected after incubation with magnesium salt ethyleneglycol tetraacetic acid (Mg‐EGTA)‐treated human serum. After incubation of serum with supernatants enriched in ANCA‐induced NETs, levels of complement components in supernatants were measured by enzyme‐linked immunosorbent assay (ELISA). Complement factor B (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b‐9 on NETs incubated with heat‐inactivated normal human serum (Hi‐NHS) or EGTA‐treated Hi‐NHS (Mg‐EGTA‐Hi‐NHS) were significantly less than that on NETs incubated with NHS or EGTA‐treated NHS (Mg‐EGTA‐NHS). NETs induced by ANCA could activate the alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a and SC5b‐9 concentration decreased from 800·42 ± 244·81 ng/ml, 7·68 ± 1·50 ng/ml, 382·15 ± 159·75 ng/ml in the supernatants enriched in ANCA induced NETs to 479·07 ± 156·2 ng/ml, 4·86 ± 1·26 ng/ml, 212·65 ± 44·40 ng/ml in the supernatants of DNase I‐degraded NETs (P < 0·001, P = 0·008, P < 0·001, respectively). NETs could activate the alternative complement pathway, and might thus participate in the pathogenesis of AAV .     

Procoagulant role of neutrophil extracellular traps in patients with gastric cancer

Background: Patients with gastric cancer (GC) commonly exhibit a hypercoagulable state that results in significant morbidity and mortality. Recent studies have shown that neutrophil extracellular traps (NETs) trigger coagulation through an intrinsic pathway and contribute to thrombus initiation and progression. In this study, we aimed to determine the procoagulant activity (PCA) of NETs in patients with GC. Methods: NET formation and their PCAs were assessed in 48 patients with GC and 36 healthy controls using immunofluorescence microscopy of neutrophil markers and extracellular DNA as well as a modified capture ELISA technique, and thrombin-antithrombin complex and clot (fibrin) spectroscopic detection, respectively. Results: Here we showed that neutrophils isolated from patients with GC displayed significantly enhanced NET formation compared with those from healthy controls; furthermore, plasma or platelets obtained from patients with GC induced control neutrophils to release NETs. In addition, NETs released by GC neutrophils significantly increased the potency of control plasma to generate thrombin and fibrin. Notably, these procoagulant effects were dramatically attenuated by application of DNase I. We further found that spontaneous NET formation in patients with GC was significantly higher than that in controls, increased with tumor- node-metastasis stage elevation, and positively correlated with thrombin-antithrombin complex levels and D-dimers. Additionally, the effect of DNase I on cell-free plasma generation of fibrin was dependent on the concentration of NET formation. Conclusion: These results suggest that GC creates a systemic environment that primes neutrophils to release procoagulant NETs. Thus, targeting NETs might improve the coagulopathy of patients with GC.     

Acetylated histones contribute to the immunostimulatory potential of neutrophil extracellular traps in systemic lupus erythematosus

In addition to disturbed apoptosis and insufficient clearance of apoptotic cells, there is recent evidence for a role of neutrophils in the aetiopathogenesis of systemic lupus erythematosus (SLE). In response to various stimuli, neutrophils can rapidly release DNA fibres decorated with citrullinated histones and anti-microbial peptides. These structures are referred to as neutrophil extracellular traps (NETs). In addition to apoptotic cell-derived microparticles, these NETs may comprise a further source of autoantigens, able to drive the autoimmune response in SLE. Our group recently identified specific histone modifications occurring during apoptosis that play an important role in the autoimmune response in SLE. In the current study, we evaluated the presence and immunostimulatory potential of these previously identified histone modifications in NETs. Compared to NETs from healthy donors, the histones present in NETs formed by SLE-derived neutrophils contain increased amounts of acetylated and methylated residues, which we previously observed to be associated with apoptosis and SLE. Treatment of neutrophils with histone deacetylase (HDAC) inhibitor Trichostatin A (TSA), prior to induction of NETosis, induced NETs containing hyperacetylated histones, endowed with an increased capacity to activate macrophages. This implies that specific histone modifications, in particular acetylation, might enhance the immunostimulatory potential of NETs in SLE.     

Neutrophil extracellular traps generation and degradation in patients with granulomatosis with polyangiitis and systemic lupus erythematosus

Neutrophils are one of the first cells to arrive at the site of infection, where they apply several strategies to kill pathogens: degranulation, respiratory burst, phagocytosis, and release of neutrophil extracellular traps (NETs). Recent discoveries try to connect NETs formation with autoimmune diseases, like systemic lupus erythematosus (SLE) or granulomatosis with polyangiitis (GPA) and place them among one of the factors responsible for disease pathogenesis. The aim of the study was to assess the NETotic capabilities of neutrophils obtained from freshly diagnosed autoimmune patients versus healthy controls. Further investigation involved assessing NETs production among treated patients. In the latter step, NETs degradation potency of collected sera from non-treated patients was checked. Lastly, the polymorphisms of the DNASE I gene among tested subjects were checked. NETs formation was measured in a neutrophil culture by fluorometry, while degradation assessment was performed with patients’ sera and extracellular source of DNA. Additionally, Sanger sequencing was used to check potential SNP mutations between patients. About 121 subjects were enrolled into this study, 54 of them with a diagnosed autoimmune disorder. Neutrophils stimulated with NETosis inducers were able to release NETs in all cases. We have found that disease affected patients produce NETs more rapidly and in larger quantities than control groups, with up to 82.5% more released. Most importantly, we showed a difference between the diseases themselves. NETs release was 68.5% higher in GPA samples when compared to SLE ones while stimulated with Calcium Ionophore. Serum nucleases were less effective at degrading NETs in both autoimmune diseases, with a reduction in degradation of 20.9% observed for GPA and 18.2% for SLE when compared with the controls. Potential therapies targeting neutrophils and NETs should be specifically tailored to the type of the disease. Since there are significant differences between NETs release and disease type, a standard neutrophil targeted therapy could prevent over-generation of traps in some cases, while in others it would deplete the cells, leaving the immune system unresponsive to primary infections.     

Interferon‐α coincides with suppressed levels of pentraxin‐3 (PTX3) in systemic lupus erythematosus and regulates leucocyte PTX3 in vitro

Dysfunctional elimination of cell debris, and the role of opsonins such as pentraxins, is of interest regarding systemic lupus erythematosus (SLE) pathogenesis. Interferon (IFN)‐α is typically elevated during SLE flares, and inhibits hepatocyte production of the pentraxin ‘C‐reactive protein’ (CRP), partly explaining the poor correlation between CRP levels and SLE disease activity. The extrahepatically produced ‘pentraxin 3’ (PTX3) shares waste disposal functions with CRP, but has not been studied extensively in SLE. We analysed serum PTX3 in SLE, and assessed its interference with IFN‐α in vitro. Serum samples from 243 patients with SLE and 100 blood donors were analysed regarding PTX3. Patient sera were analysed for IFN‐α, and genotyped for three PTX3 single nucleotide polymorphisms reported previously to associate with PTX3 levels. Stimulated PTX3 release was assessed in the presence or absence of IFN‐α in blood donor neutrophils and peripheral blood mononuclear cells (PBMC). Serum PTX3 was 44% lower in patients with SLE compared to blood donors (P < 0·0001) and correlated with leucocyte variables. Patients with undetectable IFN‐α had 29% higher median PTX3 level than patients with detectable IFN‐α (P = 0·01). PTX3 production by PBMC was inhibited by IFN‐α, whereas neutrophil degranulation of PTX3 was increased. No differences in PTX3 levels were observed between the SNPs. In conclusion, median serum PTX3 is lower in SLE (especially when IFN‐α is detectable) compared to blood donors. In addition to its potential consumption during waste disposal, it is plausible that IFN‐α also attenuates PTX3 by inhibiting synthesis by PBMC and/or exhausting PTX3 storage in neutrophil granules.