自身免疫性肝病临床及实验室特征分析

目的 比较自身免疫性肝炎(AIH)、原发性胆汁性胆管炎(PBC)和AIH/PBC重叠综合征(OS)的临床和实验室特征,探讨抗平滑肌抗体(ASMA)阳性/阴性的AIH、抗线粒体抗体(AMA)阳性/阴性的PBC的肝功能生化指标、血常规、凝血象是否存在差异,帮助临床及时诊断和治疗。方法 收集自身免疫性肝病患者169例,分析临床特征及实验室相关检测结果。结果 自身免疫性肝病(AILD)患者都可出现乏力、纳差、腹胀的症状及脾大、腹水和皮肤巩膜黄染的体征,AIH男女比例为1∶3.8,PBC男女比例为1∶11.8,AIH/PBC OS男女比例为1∶10.0。AIH患者血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)和总胆红素(TBIL)明显升高,而PBC患者碱性磷酸酶(ALP)升高明显。PBC相比AIH更容易引起血红蛋白(Hb)、血小板(PLT)的减少,而AIH更易引起凝血酶原时间(TT)的升高。AIH与PBC患者抗核抗体(ANA)阳性率差异无统计学意义(P<0.05),ASMA和AMA/AMA-M2阳性率差异有统计学意义(P<0.05)。ASMA阳性组和阴性组AIH患者的活化部分凝血酶时间(APTT),AMA阳性组和阴性组PBC患者的白细胞(RBC)比较差异有统计学意义(P<0.05)。结论 AILD有着相似的临床特征和相对特异的实验室结果,结合临床和实验室特征综合分析可帮助临床医生更好地鉴别AILD的类型,辅助临床诊断及治疗。ASMA与AIH、AMA与PBC病情的严重程度是否有明显相关性,还需进一步研究探讨。     

False positive anti-hepatitis A virus immunoglobulin M in autoimmune hepatitis/primary biliary cholangitis overlap syndrome: A case report

BACKGROUNDAutoimmune hepatitis (AIH) is an immune-mediated liver disease affecting all age groups. Associations between hepatitis A virus (HAV) and AIH have been described for many years. Herein, we report a case of an AIH/primary biliary cholangitis (PBC) overlap syndrome with anti-HAV immunoglobulin M (IgM) false positivity.CASE SUMMARYA 55-year-old man was admitted with manifestations of anorexia and jaundice along with weakness. He had marked transaminitis and hyperbilirubinemia. Viral serology was positive for HAV IgM and negative for others. Autoantibody screening was positive for anti-mitochondria antibody but negative for others. Abdominal ultrasound imaging was normal. He was diagnosed with acute hepatitis A. After symptomatic treatment, liver function tests gradually recovered. Several months later, his anti-HAV IgM positivity persisted and transaminase and bilirubin levels were also more than 10 times above of the upper limit of normal. Liver histology was prominent, and HAV RNA was negative. Therefore, AIH/primary biliary cholangitis (PBC) overlap syndrome diagnosis was made based on the “Paris Criteria”. The patient was successfully treated by immunosuppression.CONCLUSIONThis case highlights that autoimmune diseases or chronic or acute infections, may cause a false-positive anti-HAV IgM result because of cross-reacting antibodies. Therefore, the detection of IgM should not be the only method for the diagnosis of acute HAV infection. HAV nucleic acid amplification tests should be employed to confirm the diagnosis.     

自身免疫性肝病相关自身免疫性抗体的特征分析及临床应用价值

目的：观察自身免疫性肝病（AILD）相关自身免疫性抗体的特征分析及临床应用价值。方法：临床纳入自身免疫性肝炎（AIH）、原发性胆汁性肝硬化（PBC）以及病毒性肝炎患者作为研究对象,并选取健康体检者作为对照。检测每组患者的相关自身免疫指标。结果：AIH患者血清ANA阳性率明显高于PBC、病毒性肝炎以及对照组（P〈0．05）。PBC患者血PBC患者血清AMA阳性率显著高于AIH组（P〈0．05）。血清ANA在AIH以及PBC患者中均以高低度（1：1000）为主。结论：每种AILD均伴有其特征性的自身抗体,对各种类型的慢性肝病常规进行自身抗体检测对于诊断和鉴别AILD有重要的临床意义。     

自身免疫性肝炎患者的超声表现与病理及实验室检查的相关性分析

目的对照分析自身免疫性肝炎（AIH）患者的超声影像表现与临床生化指标及肝脏病理变化的相关性,研究通过超声影像诊断AIH的临床应用价值。 方法选取2014年1月至2015年12月解放军第302医院收治的68例AIH患者的超声影像学表现、病理资料及临床实验室检查结果,研究超声影像表现与病理资料及实验室检查指标的相关性。 结果超声诊断肝纤维化与病理上的"界面炎"表现与肝功的血清学指标对比,统计学上无相关性;但与病理上的"点状坏死"表现呈正相关（r=0.5099,P<0.001）。超声表现为"条索"与"结节"样改变对超声诊断AIH纤维化程度,差异有的统计学意义（t=3.9547,P<0.01）。超声检查显示肝脏的"大小"、"形态"改变与超声诊断AIH纤维化程度,差异有统计学意义（t=2.070、2.137、4.584、3.773,P均<0.05）。 结论超声影像可为AIH的诊断及其纤维化程度的评估提供客观依据。     

自身免疫性肝病及其自身抗体谱分析

目的探讨重庆地区不同类型自身免疫性肝病患者血清中自身抗体谱的特征及其临床应用价值。方法 743例肝病送检样本中81例确诊为自身免疫性肝病,将其分为3组:(1)自身免疫性肝炎(AIH)38例;(2)原发性胆汁性肝硬化(PBC)30例;(3)重叠综合征13例。用间接免疫荧光法检测抗核抗体(ANA)、抗线粒体抗体(AMA)、抗平滑肌抗体(SMA)、抗肝肾微粒抗体(LKM)、抗可溶性肝抗原(SLA)等,用酶联免疫吸附试验(ELISA)定量测定抗线粒体M2亚型。结果 743例中诊断为AIH、PBC和重叠综合征分别为送检标本的5.11%、4.04%和1.75%,总计10.9%。AIH患者ANA阳性率为78.9%,AMA及M2亚型阳性率为18.4%,SMA阳性率为7.89%;PBC患者ANA阳性率为73.3%;AMA和M2阳性率为26.7%;重叠综合征患者ANA及AMA阳性率为100%。结论自身免疫性肝病抗体谱检测有助于自身免疫性肝病诊断,非病毒性肝炎诊断时应考虑自身免疫性肝病。     

自身免疫性肝病

自身免疫性肝病系机体自身免疫反应过度造成肝组织损伤的疾病，主要包括自身免疫性肝炎（AIH）、发性胆汁性肝硬化（PBC）、原发性硬化性胆管炎（PSC）和变异综合征等，其病因可能与遗传易感性和分子模拟机制有关。本文重点介绍病因、发病机制、临床表现、诊断和治疗。血清自身抗体ANA，SMA，AMA，LKM，pANCA，抗-SLA，AMA—M2检测有助于明确诊断。AIH可采用免疫抑制剂和皮质激素治疗，PBC和PSC可选用熊去氧胆酸和皮质激素，终末期可考虑采用肝移植治疗。     

A case report of successful treatment with plasma exchange for adult‐onset Still's disease with autoimmune hepatitis

Adult onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown etiology and pathogenesis. The disease is characterized by typical spiking fever with evanescent rash, sore throat, polyarthralgias or polyarthritis, and involvement of various organs. Most of the reported cases with liver involvement occurred during the period of treatment with hepatotoxic drugs, whereas AOSD associated autoimmune hepatitis (AIH) is extremely rare. AIH may be an indicator of the poor prognosis of AOSD. Herein we describe a case of successful treatment with plasma exchange for AOSD‐associated AIH. J. Clin. Apheresis 2010. © 2010 Wiley‐Liss, Inc.     

Ⅰ型自身免疫性肝炎患者抗Ro52抗体的检测及临床意义

目的 探讨Ⅰ型自身免疫性肝炎患者抗Ro52抗体的临床意义.方法 采用免疫印记法检测54例Ⅰ型自身免疫性肝炎（autoimmune hepatitis,AIH）患者血清中的抗Ro52抗体,根据检测结果分为抗Ro52抗体阳性组与阴性组,并对两组检测结果及临床资料进行回顾性分析.结果 54例Ⅰ型AIH患者中,抗Ro52抗体阳性20例（37％）.抗Ro52抗体阳性组与阴性组Ⅰ型AIH患者的抗核抗体（ANA分布主要见于滴度1∶320～1∶1000）.20例抗Ro52抗体阳性患者中,5例（25％）抗可溶性肝原（抗SLA/LP）抗体阳性;12例（60％）同时抗Ro60阳性.抗Ro52抗体阳性组出现肝病相关并发症的比例高于阴性组,但差别无统计学意义（65％vs.38.2％;x2 =3.613,P＞0.05）.抗Ro52抗体阳性组合并肝外自身免疫性疾病的比例显著高于阴性组（x2 =4.290,P=0.038）.抗Ro52抗体阳性组IgG水平显著高于阴性组（t=3.014,P=0.04）.结论 抗Ro52抗体阳性可提示AIH患者伴发肝内或肝外并发症几率升高;抗Ro52抗体可能与IgG共同作用,参与Ⅰ型AIH的发病.     

Defective removal of ribonucleotides from DNA promotes systemic autoimmunity

Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2–associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage–associated pathways in the initiation of autoimmunity.     

Clinical outcomes and survival analysis in patients with psycho-cardiological disease: a retrospective analysis of 132 cases

ObjectivesThe deleterious effects of psychological problems on coronary heart disease (CHD) are not satisfactorily explained. We explored influential factors associated with mortality in psycho-cardiological disease in a Chinese sample.MethodsOf 7460 cardiac patients, we selected 132 patients with CHD and mental illness. Follow-up was conducted via telephone. We analyzed clinical characteristics, clinical outcomes, and survival.ResultsThe clinical detection rate of psycho-cardiological disease in the overall patient population was 1.8%. Of these, 113 patients completed follow-up; 18 died owing to cardiovascular diseases during follow-up. Kaplan–Meier analysis showed dysphagia, limb function, self-care ability, percutaneous coronary intervention, low-density lipoprotein, total cholesterol, pro-brain natriuretic peptide and high-sensitivity (hs) troponin T had significant associations with cumulative survival. Cox regression analysis showed total cholesterol (hazard ratio [HR]: 2.765, 95% confidence interval [CI]: 1.001–7.641), hs troponin T (HR: 4.668, 95% CI: 1.293–16.854), and percutaneous coronary intervention (HR: 3.619, 95% CI: 1.383–9.474) were independently associated with cumulative survival.ConclusionsThe clinical detection rate of psycho-cardiological disease was far lower than expected. Normal total cholesterol and hs troponin T were associated with reduced cardiovascular disease mortality over 2 years. Percutaneous coronary intervention is a prognostic risk factor in patients with psycho-cardiological disease.     

Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6ΔTEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6ΔTEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6ΔTEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6ΔTEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this disease.     

自身免疫性肝炎44例分析

目的　探讨自身免疫性肝炎(autoimmunehepatitis,AIH)的免疫学实验诊断特点。方法　观察 44例AIH的临床表现,并分析有关实验室检查资料。结果　本组患者临床症状不典型,肝功能各项指标普遍异常,有 38例患者抗核抗体 (antinuclearantibodies,ANA)阳性, 29例抗平滑肌抗体 (smoothmuscleantibodies,SMA)阳性, 22例抗线粒体抗体 (antimitochondrialantibodies,AMA)阳性(其中 1例M2阳性), 2例抗肝肾微粒体(anti liver/kidneymicrosomalantibodies,anti- LKM)- 1抗体阳性, 4例抗可溶性肝抗原抗体(anti solubleliverantigenantibodies,anti- SLA)阳性。结论　AIH无典型临床症状,患者可以通过自身抗体的检测结合临床表现获得诊断。     

Champagne bottle neck sign in a patient with Moyamoya syndrome

The champagne bottle neck (CBN) sign refers to a reduction in the diameter of the proximal portion of the internal carotid artery that resembles a CBN, and is a characteristic feature of Moyamoya disease. A 43-year-old woman with an infarction of the posterior limb of the left internal capsule was diagnosed with Moyamoya syndrome associated with Graves’ disease. The CBN sign was observed bilaterally. Cerebral revascularization surgery was performed, including left-sided superficial temporal artery to middle cerebral artery anastomosis. During four years of follow-up, she maintained a euthyroid state and did not have any further cerebral ischemic events. The CBN signs remained unchanged on both sides during this time. This is the first report of the CBN sign in a patient with Moyamoya syndrome associated with Graves’ disease.     

Association between the liver fat score (LFS) and cardiovascular diseases in the national health and nutrition examination survey 1999–2016

BackgroundThe liver fat score (LFS) has been proposed to be a simple non-invasive marker of non-alcoholic fatty liver disease (NAFLD), which is highly prevalent in the general population. We tested its association with cardiovascular diseases (CVDs) and prognosis.Methods17,244 adult participants from the National Health and Nutrition Examination Survey 1999–2016 were included. LFS is calculated from variables including serum aspartate transaminase/alanine transaminase (AST/ALT) ratio, fasting serum aspartate transaminase (AST) level, fasting serum insulin level, presence of metabolic syndrome and diabetes mellitus. In cross-sectional analysis, logistic regression was used to examine the association of the LFS with coronary heart disease (CHD), myocardial infarction (MI), congestive heart failure (CHF), stroke and angina pectoris. Mortality during follow-up was analysed using Cox proportional hazard regression.ResultsLFS was associated with CHD (adjusted odds ratio [OR]: 1.09 per standard deviation [SD], 95% confidence interval [95% CI]: 1.03–1.15) (p = .003), CHF (1.11, 1.04–1.18) (p = .003) and angina pectoris (1.08, 1.02–1.13) (p = .005). LFS was not associated with MI or stroke, but was associated with increased all-cause and cardiovascular mortality with hazard ratios (HRs) of 1.10 (95% CI: 1.07–1.13) (p < .001) and 1.12 (95% CI: 1.06–1.17) (p < .001), respectively.ConclusionsNAFLD is usually asymptomatic, but this large study of a large general population shows that LFS is associated with CHD, CHF, angina pectoris, cardiovascular and all-cause mortality. Determining the LFS is worthwhile, as it identifies people with NAFLD, who may also be at increased cardiovascular risk.

Key Messages

• Liver fat score (LFS), a non-invasive marker of non-alcoholic fatty liver disease (NAFLD), is associated with coronary heart disease (CHD), congestive heart failure (CHF) and angina.
• LFS is also associated with increased cardiovascular and all-cause mortality.
• Determining the LFS is worthwhile as it identifies people with NAFLD as well as increased cardiovascular risk.

     

自身免疫性肝炎与系统性红斑狼疮肝损的异质性

目的 :研究自身免疫性肝炎 (AutoimmuneHepatitis ,AIH)的临床表现 ,肝活检病理以及与系统性红斑狼疮 (SLE)肝损害的异同。方法 :回顾性总结 15例AIH及 2 0例SLE肝损害患者的临床及肝活检病理。结果 :AIH表现为丙氨酸转氨酶(ALT)、天冬氨酸转氨酶 (AST)异常 ,高球蛋白、高γ球蛋白血症 ,存在多种自身抗体 ,伴发自身免疫性疾病 ,病理以慢性肝炎为特点 ;SLE肝损常表现在初发患者一过性ALT、AST、球蛋白、球蛋白升高 ,病理为非特异性肝损。球蛋白、γ球蛋白、免疫球蛋白G(IgG)在AIH中极显著高于SLE的肝损 (P <0 .0 0 1) ,抗双链DNA抗体 (ds-DNA)在SLE肝损病人极显著高于AIH(P <0 .0 0 1)。结论 :AIH肝病损严重 ,肝外病变多样 ,有多系统损害倾向 ,是完全有别于SLE肝损的独立疾病     

High-molecular intestinal alkaline phosphatase in chronic liver diseases

The presence of high-molecular intestinal alkaline phosphatase (HIALP) different from bone ALP detected in the alpha(2)beta region was recently clarified. In this study we used a novel method in which HIALP was detected after conversion to ALP(5) by protease to investigate the clinical significance of the appearance of HIALP in patients with chronic liver disease. The subjects were 241 patients with chronic liver disease. When a decrease in ALP(3) in the alpha(2)beta region and an increase in ALP(5) in the beta region were noted, the patient was judged HIALP-positive. In the patients with chronic liver disease, the total ALP activity (T-ALP) increased with progression of the pathology in the order of chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). HIALP appeared in 22.4% and 49.3% of patients with CH and LC, respectively, but the positivity rate decreased to 30.4% in HCC. As autoimmune liver diseases, primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) were investigated. T-ALP was lower in PBC+AIH than in LC and HCC, but the HIALP-positive rate was high (44.4%). The HIALP-positive rate was dependent on ABO blood groups, and was high in blood groups B and O. In conclusion, the HIALP-positive rate was particularly high in patients with chronic liver disease, and was related to the pathological progression, which suggests that the method is clinically useful.     

原发性胆汁性肝硬化和自身免疫性肝炎重叠综合征患者的临床特征分析

目的 分析原发性胆汁性肝硬化（PBC）和自身免疫性肝炎（AIH）重叠综合征（PBC／AIH重叠综合征）患者的临床表现和肝组织病理学的特点。方法 对124例自身免疫性肝病患者的临床资料进行分析，根据国际自身免疫性肝炎小组修订的诊断标准，筛选出19例PBC／AIH重叠综合征患者，分析比较PBC／AIH重叠综合征和单纯PBC、AIH患者的临床表现、肝组织病理学变化。结果 124例自身免疫性肝病患者中19例PBC／AIH重叠综合征，单纯PBC55例、AIH49例，原发性硬化性胆管炎（PSC）1例，分别占15．32％、44．35％、39．52％和0．81％。PBC／AIH重叠综合征实验室检查具有AIH的特点，如血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、免疫球蛋白G的明显升高，同时具有PBC的特点，如转肽酶、碱性磷酸酶、免疫球蛋白M的显著增高；自身抗体检测可见抗核抗体、抗平滑肌抗体、抗线粒体抗体、M2抗体阳性；肝组织病理结果显示，兼有PBC和AIH的特点，如界面炎和碎屑样坏死，汇管区浆细胞浸润，胆管不同程度病变。结论 PBC／AIH重叠综合征并非罕见，它的临床表现、肝组织病理学具有PBC和AIH的双重特征，应对此病充分认识，探索有效的治疗方案。     

High prevalence of celiac disease in autoimmune hepatitis detected by anti-tissue tranglutaminase autoantibodies

Celiac disease (CD) may be found in association with other autoimmune diseases. We investigated the relation between autoimmune hepatitis (AIH) and CD by assessing the prevalence of IgA and IgG anti-tissue transglutaminase (tTG) antibodies in AIH, and by verifying whether the findings were associated with clinical and histological features of CD. Forty-seven consecutive patients with AIH (type I: n = 39; type II: n = 8) were studied. One hundred patients with chronic hepatitis C, and 120 healthy blood donors were also studied as controls. We analyzed sera for the presence of IgA and IgG anti-tTG antibodies using a specific human recombinant tTG immunoenzymatic assay. Anti-tTG positive patients and controls were further tested for anti-endomysium antibodies (EMA) and HLA typing, and those found positive by either of these tests underwent duodenal biopsy to confirm a possible diagnosis of CD. Three of the 47 AIH patients (6.4%) were positive for IgA anti-tTG and EMA antibodies, and were subsequently confirmed to be affected with CD by small-bowel biopsy findings. No IgG anti-tTG positivity was found in the AIH patients. None of the controls were positive for IgA anti-tTG, and only one with chronic hepatitis C had a low positive reaction for IgG anti-tTG, which resulted as a false positive. The crude prevalence rate of CD in AIH was 63.8 per 1,000 (95% CI, 13.2-186.1), and it was significantly higher than that found in the general population in Italy (4.9 per 1,000; 95% CI, 2.8-7.8). The results of this study showed a high prevalence of CD in patients with AIH. For this reason, early serological screening testing for CD is strongly recommended for all AIH patients.     

The Incidence of Diabetes Among 2,777,768 Veterans With and Without Recent SARS-CoV-2 Infection

OBJECTIVETo examine associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 with incident diabetes.RESEARCH DESIGN AND METHODSWe conducted a retrospective cohort study using Veterans Health Administration data. We defined all patients without preexisting diabetes with one or more nasal swabs positive for SARS-CoV-2 (1 March 2020–10 March 2021; n = 126,710) as exposed and those with no positive swab and one or more laboratory tests (1 March 2020–31 March 2021; n = 2,651,058) as unexposed. The index date for patients exposed was the date of first positive swab and for patients unexposed a random date during the month of the qualifying laboratory test. We fit sex-stratified logistic regression models examining associations of SARS-CoV-2 with incident diabetes within 120 days and all follow-up time through 1 June 2021. A subgroup analysis was performed among hospitalized subjects only to help equalize laboratory surveillance.RESULTSSARS-CoV-2 was associated with higher risk of incident diabetes, compared with no positive tests, among men (120 days, odds ratio [OR] 2.56 [95% CI 2.32–2.83]; all time, 1.95 [1.80–2.12]) but not women (120 days, 1.21 [0.88–1.68]; all time, 1.04 [0.82–1.31]). Among hospitalized participants, SARS-CoV-2 was associated with higher risk of diabetes at 120 days and at the end of follow-up in men (OR 1.42 [95% CI 1.22–1.65] and 1.32 [1.16–1.50], respectively) but not women (0.72 [0.34–1.52] and 0.80 [0.44–1.45]). Sex ∗ SARS-CoV-2 interaction P values were all <0.1.CONCLUSIONSSARS-CoV-2 is associated with higher risk of incident diabetes in men but not in women even after greater surveillance related to hospitalization is accounted for.     

Protein microarray analysis reveals BAFF-binding autoantibodies in systemic lupus erythematosus

Autoantibodies against cytokines, chemokines, and growth factors inhibit normal immunity and are implicated in inflammatory autoimmune disease and diseases of immune deficiency. In an effort to evaluate serum from autoimmune and immunodeficient patients for Abs against cytokines, chemokines, and growth factors in a high-throughput and unbiased manner, we constructed a multiplex protein microarray for detection of serum factor–binding Abs and used the microarray to detect autoantibody targets in SLE. We designed a nitrocellulose-surface microarray containing human cytokines, chemokines, and other circulating proteins and demonstrated that the array permitted specific detection of serum factor–binding probes. We used the arrays to detect previously described autoantibodies against cytokines in samples from individuals with autoimmune polyendocrine syndrome type 1 and chronic mycobacterial infection. Serum profiling from individuals with SLE revealed that among several targets, elevated IgG autoantibody reactivity to B cell–activating factor (BAFF) was associated with SLE compared with control samples. BAFF reactivity correlated with the severity of disease-associated features, including IFN-α–driven SLE pathology. Our results showed that serum factor protein microarrays facilitate detection of autoantibody reactivity to serum factors in human samples and that BAFF-reactive autoantibodies may be associated with an elevated inflammatory disease state within the spectrum of SLE.