Serum Levels Of Autoantibodies Research Articles

Anti-CD11b antibody treatment suppresses the disease conditions in rheumatoid arthritis (RA)-prone, FcγRIIB-deficient mice

Abstract Previously we established a RA-prone, FcγRIIB deficient mouse strain (KO1). Anti-mouse CD11b mAb (5C6) has been reported to inhibit the recruitment of CD11b+ myelomonocytic cells from the blood to the inflammatory site. The CD11b+ cells include neutrophils and monocytes, both of which are known to play important roles in the development of RA. In this study, we treated KO1 mice with 5C6 mAb to examine its effects on RA development. Four-month-old preclinical KO1 mice were treated for 6 months; with 5C6, rat IgG as a control, or none. Among the 3 groups of mice, the severity of RA and immunological abnormalities were compared. RA-related factors in the ankle joints, spleens, and peripheral blood cells were examined. The 5C6 treatment ameliorated the conditions of RA in KO1 mice, along with the decreases in inflammatory-cell infiltration and osteoclast formation. Transcriptional level analysis for the ankle joints showed that the 5C6 treatment down-regulated the expressions of RANK, RANKL, MCP-1, RANTES, TNFα, and IL-6; and up-regulated that of osteoprotegerin, the decoy receptor for RANKL. Suppression of RA was associated with the lower serum level of autoantibodies, and the decreased frequency of activated B cells. Expressions of B-cell stimulating cytokines were suppressed in the spleens and peripheral leukocytes of the 5C6-treated mice. While untreated KO1 mice spontaneously developed marked monocytosis, the frequency of monocytes was significantly downregulated in the 5C6-treated mice. It is thought that the 5C6-mediated suppression of RA is caused by the decreased numbers of inflammatory cells and monocytes per se at the joints; also secondarily by the reduced amounts of B-cell stimulating cytokines, leading less autoantibodies.

Low Levels of IgM and IgA Recognizing Acetylated C1-Inhibitor Peptides Are Associated with Systemic Lupus Erythematosus in Taiwanese Women.

The objective of this study was to identify novel acetylation (Ac) modifications of the C1-inhibitor (C1-INH) and explain the association of the levels of autoantibodies against acetylated C1-INH peptides with the risk of developing systemic lupus erythematosus (SLE). Ac modifications of the C1-INH were identified and validated through in-gel digestion, nano-liquid chromatography-tandem mass spectrometry, immunoprecipitation, and Western blotting by using serum protein samples obtained from patients with SLE and age-matched healthy controls (HCs). In addition, the levels of serum C1-INH, Ac-protein adducts, and autoantibodies against unmodified and acetylated C1-INH peptides were measured. C1-INH levels in patients with SLE were significantly lower than those in HCs by 1.53-fold (p = 0.0008); however, Ac-protein adduct concentrations in patients with SLE were significantly higher than those in HCs by 1.35-fold (p = 0.0009). Moreover, immunoglobulin M (IgM) anti-C1-INH367–385 Ac and IgA anti-C1-INH367–385 Ac levels in patients with SLE were significantly lower than those in HCs. The low levels of IgM anti-C1-INH367–385 (odds ratio [OR] = 4.725, p < 0.001), IgM anti-C1-INH367–385 Ac (OR = 4.089, p = 0.001), and IgA anti-C1-INH367–385 Ac (OR = 5.566, p < 0.001) indicated increased risks for the development of SLE compared with HCs.

Prevalence of Autoimmune Gastritis in Individuals Undergoing Medical Checkups in Japan.

Objective Based on both endoscopic findings and serum auto-antibody levels, we determined the prevalence of autoimmune gastritis (AIG), which has not been previously reported, in individuals who underwent health checkup examinations in Japan. Methods At total of 6,739 subjects (4,288 males, 2,451 females; mean age 52.1 years) underwent an upper gastrointestinal endoscopic examination as part of an annual medical checkup. Those suspected to have AIG based on endoscopic evidence of proximal-predominant gastric mucosal atrophy were further examined for the presence of anti-parietal cells and anti-intrinsic factor antibodies, with a final diagnosis of AIG made in cases found to be positive for either or both of those factors. Results Of the 6,739 examined subjects, 46 were suspected to have AIG based on the endoscopic findings, of whom 33 were finally diagnosed with AIG, for an overall prevalence 0.49% (females 0.65%, males 0.40%). Seven with AIG also had thyroid disease, including Hashimoto's and Basedow disease, while none with AIG showed anemia in blood test findings. The prevalence of AIG was not different regardless of the H. pylori infection status (negative, positive, post-eradicated). Conclusion In individuals who underwent an upper gastrointestinal endoscopic examination as part of an annual checkup in Japan, the prevalence of AIG was 0.49%. We concluded that it is not uncommon for asymptomatic and healthy individuals to have AIG, and propose that additional studies are needed to clarify its prevalence as well as to establish the criteria used for diagnosis.

Elevated levels of autoantibodies against EXD2 and PHAX in the sera of patients with chronic thromboembolic pulmonary hypertension

While circulating autoantibodies have been detected in patients with several cardiovascular diseases, such studies have not been performed for chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Here we investigated the production of certain auto-antibodies in CTEPH patients. Initial screening was performed in 5 CTEPH patients and 5 healthy donors (HDs) using a ProtoArray Human Protein Microarray v5.1 containing 9,375 human proteins, and we selected 34 antigens recognized by IgG antibodies more strongly in the sera of CTEPH patients than in the sera of HDs. In subsequent second/third analyses, we validated the auto-antibody level using amplified luminescent proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) in 96 CTEPH patients and 96 HDs as follows: At the second screening, we used 63 crude peptides derived from those selected 34 antigens and found that the serum levels of autoantibodies for 4 peptides seemed higher in CTEPH patients than in HDs. In third analysis, we used the purified peptides of those selected in second screening and found that serum antibodies against peptides derived from exonuclease 3'-5' domain-containing 2 (EXD2) and phosphorylated adaptor for RNA export (PHAX) were significantly higher in CTEPH patients than in HDs. The serum antibody levels to these antigens were also elevated in PAH patients. The titers against EXD2 peptide decreased after surgical treatment in CTEPH patients. These autoantibodies may be useful as biomarkers of CTEPH and PAH, and further investigations may provide novel insight into the etiology.

The Induction of Autoimmune Arthritis and Sex Differences in Mice Impact the Lung Inflammatory Response to Repetitive Inhalant Organic Dust Extract Exposures

Inflammatory lung diseases are often associated with systemic autoimmunity, and sex differences have been independently described. Men are at increased risk of occupational exposure-associated rheumatoid arthritis (RA) and extra-articular manifestations. Because agriculture work is associated with both chronic lung disease and RA, we sought to determine whether induction of autoimmune arthritis and sex influence airway response to organic dust extract (ODE). Arthritis prone, DBA/1J male and female mice (8 week), were treated daily with ODE or saline for 5 weeks with collagen-induced arthritis (CIA) induced on days 1 and 21. Treatment groups included Sham (saline injection/saline inhalation), CIA (CIA/saline), ODE (saline/ODE); CIA+ODE (CIA/ODE). Bronchoalveolar lavage fluids, lung tissues, serum, and bones were collected. ODE induced airway neutrophil influx, increases in inflammatory mediators (TNF-α, IL-6, CXCL1, CXCL2), release of fibronectin (but not hyaluronan), and increased lung collagen staining as compared to sham. Co-exposure (CIA+ODE) resulted in reduced neutrophil and inflammatory mediator responses as compared to ODE alone, but lung tissue levels of hyaluronan, fibronectin and collagen staining were either augmented or remained increased in CIA+ODE. Arthritis inflammatory scores and serum anti-cyclic citrullinated peptide antibody were greatest in CIA+ODE. Compared to male mice, female mice demonstrated reduced ODE-induced mediator release, hyaluronan and fibronectin as well as lower arthritis scores and serum autoantibody levels with co-exposure. Autoimmune arthritis induction modulates the lung response to inhalant ODE exposure, impacting the inflammatory-interstitial disease process. Congruent with epidemiologic findings, male mice were most susceptible to lung and articular disease resulting from ODE.

Autoimmune hepatitis: Appraisal of current treatment guidelines

Autoimmune hepatitis affects patients of all ages and gender, across all geographic regions. Although still rare, its incidence and prevalence are increasing. Genetic predisposition conveyed by human leucocyte antigen is a strong risk factor for the disease and may be responsible in part for the wide variation in presentation in different geographic regions. Our understanding of the underlying pathogenic mechanisms is evolving and may lead to development of more targeted immunotherapies. Diagnosis is based on elevated levels of serum aminotransferases, gamma globulins, autoantibodies and characteristic findings on histology. Exclusion of other causes of chronic hepatitis is important. Although undiagnosed disease is associated with poor outcomes, it is readily treatable with timely immunosuppressive therapy in the majority of patients. International guidelines are available to guide management but there exists a disparity in the standard treatment regimens. This minireview aims to review the available guidelines and summarize the key recommendations involved in management of this complex autoimmune disease.

Ten-year observation of patients with primary Sjögren's syndrome: Initial presenting characteristics and the associated outcomes.

Primary Sjögren's syndrome (pSS) is a prototypical systemic autoimmune disease that manifests with various signs and symptoms. Although some studies have examined these manifestations over the long-term course of the disease, the association between initial clinical and immunological factors and subsequent long-term manifestations has not been fully elucidated. The aim of this study is to identify initial clinical and immunological factors associated with subsequent manifestations in patients with pSS. A retrospective review was performed in pSS patients who were followed up over a 10-year period in our department. Clinical and immunological data, including serum immunoglobulin (Ig) and autoantibody levels, were collected and statistically analyzed. We analyzed 91 patients who were followed up in our department. The proportion of patients with extraglandular involvement decreased from 90% to 73%, while eight patients developed extraglandular organ involvement. Extraglandular involvement at 10years more frequently occurred in patients with hyper-IgG than those without hyper-IgG at initial testing (P<0.01). Extraglandular organ involvement at 10years more frequently occurred in rheumatoid factor (RF)-positive patients at the time of SS diagnosis (P<0.05). Malignancy occurred in 9% of patients. Age, lower CH50 and thrombocytopenia were significantly associated with malignancy. Extraglandular organ involvement was associated with the presence of hyper-IgG and RF positivity (P<0.01 and P<0.05). Our study identified important initial clinical and immunological factors associated with subsequent manifestations in patients with pSS over a long follow-up period. pSS patients with RF and hyper-IgG at diagnosis may have a higher risk of subsequent extraglandular involvement.

Micronuclei frequency in peripheral blood lymphocytes and levels of anti-p53 autoantibodies in serum of residents of Kowary city regions (Poland) with elevated indoor concentrations of radon

IntroductionNinety four residents of Kowary city (Poland) have been investigated for environmental radon exposure that ranged from 0.24 WLM to 9.6 WLM (activity concentration range: 35–2700 Bq/m3). Kowary was chosen because of uranium mineralisation in its close vicinity. MethodWhole population studied was divided into two groups: exposed to low radon activity concentrations resulting in the exposure of ≤0.55 WLM (value corresponding to the exposure to 100 Bq/m3 during whole year), and exposed to high radon activity concentration (>0.55 WLM). In the two groups two selected biomarkers in blood were assessed: the cytokinesis-block micronucleus assay (CBMN) on peripheral blood lymphocytes (PBL), and the levels of anti-p53 antibodies in serum measured because some data indicate increased expression of the antibodies in individuals after exposure to DNA damaging agents including radon. The potential confounding factors known to influence micronuclei (MN) frequency were also measured in serum: vitamin B12, folic acid, as well as total calcium. ResultsIn the present study no significant correlation was found between MN frequency in PBL and radon exposure. Among all persons investigated only 11 had detectable levels of the anti-p53 antibodies, whereas only 3 persons had positive result. Therefore, the group was too small to perform any meaningful statistical analysis and to conclude on any association. Cigarette smoking did not significantly influence the number of MN. There was a significant positive correlation observed between MN frequency and age, as well as higher MN frequency was detected in women. ConclusionThe problem of the radon exposure is still unresolved and needs further studies on bigger human cohorts in order to search for more sensitive biomarkers.

Do elevated autoantibodies in patients with multiple sclerosis matter?

The incidence and clinical impact of serum autoantibodies in patients with multiple sclerosis (MS) are controversially discussed. The aim of the study was to reassess the value of elevated serum autoantibodies in our MS study cohort. In total, 176 MS patients were retrospectively analyzed for coexistence and clinical impact of increased serum autoantibody levels. The 18.8% of the MS cohort showed elevated serum autoantibody levels, but only 10.2% of all MS patients were diagnosed with a further autoimmune disease (AI). Patients with elevated serum autoantibodies (AABS) were not significantly more often diagnosed with a clinical manifest AI as compared to patients with negative autoantibodies (P=0.338). MS patients with disease duration of more than 10years showed no significant increase of positive autoantibodies as compared to patients with a more recent disease onset (P=1). MS patients with elevated serum autoantibodies did not exhibit a significantly worse disease course (P=0.428). According to our data, elevated serum autoantibodies do not have the potential to serve as a prognostic tool for disease severity in patients with MS Since MS patients with positive serum AABS did not significantly more often suffer from clinical manifest AIs than MS patients with negative serum AABS, the role of routine testing of serum AABS in MS patients should be critically called into question.

Neurobiological parameters in quantitative prediction of treatment outcome in schizophrenic patients.

The aim of the study was to reveal the set of neurobiological parameters informative for individual quantitative prediction of therapeutic response in schizophrenic patients. Correlation and regression analyses of quantitative clinical scores (by Positive And Negative Syndromes Scale- PANSS), together with background EEG spectral power values and four immunological parameters: enzymatic activity of leukocyte elastase and of alpha-1 proteinase inhibitor, as well as serum levels of autoantibodies to common myelin protein and to nerve growth factor, were performed in 50 patients (all females, aged 32.9±10.8 years) with hallucinatory-delusional disorders in the frames of attack-like paranoid schizophrenia. Background neurobiological data obtained before the beginning of syndrome based treatment course (at visit1) were matched with PANSS clinical scores of the same patients after treatment course at the stage of remission establishment (at visit2). The multiple linear regression equations were created which contained only 3 to 4 (from initial 80) background EEG parameters and one of four immunological parameters. These mathematical models allowed prediction from 65% to 76% of PANSS scores variance after treatment course (at visit2). The data obtained may be used for elaboration of methods of individual quantitative prediction of treatment outcome in schizophrenic patients.

Modified scanning electron microscopy reveals pathological crosstalk between endothelial cells and podocytes in a murine model of membranoproliferative glomerulonephritis

This study evaluated endothelial cells and podocytes, both being primary components of the glomerular filtration barrier, in the progression of membranoproliferative glomerulonephritis (MPGN) using modified scanning electron microscopy (mSEM) analysis. BXSB/MpJ-Yaa model mice exhibited autoimmune-mediated MPGN characterised by elevated serum autoantibody levels, albuminuria, renal dysfunctional parameters, and decreased glomerular endothelial fenestrations (EF) and podocyte foot process (PFP) effacement with immune cell infiltration. Similar to transmission electron microscopy, mSEM revealed a series of pathological changes in basement membrane and densities of EF and PFP in BXSB/MpJ-Yaa compared with control BXSB/MpJ at different stages. Further, immunopositive area of endothelial marker (CD34), podocyte functional molecules (Nephrin, Podocin, Synaptopodin, and Wilms’ tumour 1 (WT1)), and vascular endothelial growth factor A (VEGF A) significantly decreased in the glomerulus of BXSB/MpJ-Yaa compared with BXSB at final stage. The indices of glomerular endothelial injuries (EF density and immunopositive area of CD34 and VEGF A) and podocyte injuries (PEP density and immunopositive area of podocyte functional molecules) were also significantly correlated with each other and with indices of autoimmune disease and renal dysfunction. Thus, our results elucidated the pathological crosstalk between endothelial cells and podocytes in MPGN progression and the usefulness of mSEM for glomerular pathological analysis.

TLR4+CXCR4+ plasma cells drive nephritis development in systemic lupus erythematosus

ObjectivesIn patients with systemic lupus erythematosus (SLE), immune tolerance breakdown leads to autoantibody production and immune-complex glomerulonephritis. This study aimed to identify pathogenic plasma cells (PC) in the development of...

The effects of superovulation with gonadotropins on autoantibody levels in patients undergoing assisted reproductive cycles.

To evaluate the effect of controlled ovarian stimulation (COH) with gonadotropins on the serum levels of autoantibodies in the women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles and to compare basal levels of these autoantibodies between groups according to history of COH. This prospective cohort study was performed from October 2014 to March 2016 in the Royan Institute. The volunteered infertile women with regard to the inclusion criteria, who underwent IVF/ICSI cycles, were recruited. The COH was performed according to standard long GnRH agonist protocol. The mean levels of the autoantibodies including anti-nuclear, anti-smooth muscle, anti-ovarian, anti-mitochondrial, anti β2-glycoprotein I, anti-parietal cell and anti-follicle-stimulating hormone antibodies were measured at three time points: on the 3-5days of the menstrual cycle, 1week after starting of COH and the ovum pick-up (OPU) day. Of all participants (n = 189), 73 women had history of COH (group B) and 116 women did not have such history (group A). The analysis indicated that the autoantibodies changes during COH were similar in both groups. COH has no significant impact on the level of autoantibodies during the stimulation cycle. Multiple logistic regression analysis showed that the serum levels of anti-smooth muscle antibody on OPU day was the positive predictive factors for live birth following ART cycles in the studied population. No significant effect of COH on the studied autoantibodies by the time of OPU was found but further studies are required to interpret these results.

Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission.

To examine the expression and changes in function of circulating CD4+CXCR5+FoxP3+ follicular Treg (Tfr) cells in patients with active rheumatoid arthritis (RA) and in patients with RA in stable remission, and to clarify the role of Tfr cells in the pathogenesis of RA. Levels of Tfr cells and follicular helper T (Tfh) cells in the peripheral blood of 39 patients with active RA, 39 patients with RA in stable remission, and 33 healthy controls were detected by flow cytometry. The function of Tfr cells was measured by coculturing them with Tfh cells and B cells. Activated CD45RA-FoxP3high Tfr cells were also analyzed. Clinical indicators, including serum Ig and autoantibody levels, were tested, and correlations with Tfr cells were systematically analyzed. The Disease Activity Score in 28 joints (DAS28) was calculated, and correlation analysis with Tfr cells was conducted. The level of CD4+CXCR5+FoxP3+ Tfr cells and the Tfr cell:Tfh cell ratio in peripheral blood from patients with RA in stable remission were significantly increased compared with the same measures in patients with active RA and in healthy controls. The function of Tfr cells was enhanced, and the activated CD45RA-FoxP3high Tfr cell subset was increased in patients with RA in stable remission compared with healthy controls. Furthermore, the number of Tfr cells in RA patients was inversely correlated with IgG, rheumatoid factor, and anti-cyclic citrullinated peptide as well as with the DAS28. Circulating Tfr cells are increased as patients with RA achieve stable remission of disease, and increased Tfr cells can suppress autoimmunity in RA patients to stabilize their condition. Our results provide novel insight into RA pathogenesis.

Oral lichen planus - Differential diagnoses, serum autoantibodies, hematinic deficiencies, and management.

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disease that occurs more frequently in middle-aged and elderly female patients. Previous studies indicate that OLP is a T-cell dysfunction-induced localized autoimmune disease. Clinically, six types of OLP, namely reticular, papular, plaque-like, atrophic/erosive, ulcerative, and bullous types, can be identified. OLP more commonly affects buccal mucosa, tongue, and gingiva. It always has a bilateral and symmetric distribution of the oral lesions. Plaque-like and atrophic/erosive OLP may be misdiagnosed as oral leukoplakia and oral erythroleukoplakia, respectively. Our previous study found serum autoantibodies in 195 (60.9%) of the 320 OLP patients. Specific serum anti-nuclear, anti-smooth muscle, anti-mitochondrial, gastric parietal cell, thyroglobulin, and thyroid microsomal autoantibodies are present in 28.1%, 8.4%, 1.6%, 26.3%, 21.3%, and 24.4% of 320 OLP patients, respectively. Furthermore, we also discovered that 21.9%, 13.6%, 7.1%, 0.3%, and 14.8% of 352 OLP patients have hemoglobin, iron, vitamin B12, and folic acid deficiencies, and abnormally high serum homocysteine level, respectively. Therefore, it is very important to examine the serum autoantibody, hematinic and homocysteine levels in OLP patients before starting the treatments for OLP patients. Because OLP is an immunologically-mediated disease, corticosteroids are the drugs of choice for treatment of OLP.

Anti-CD11b antibody treatment suppresses the osteoclast generation, inflammatory cell infiltration, and autoantibody production in arthritis-prone Fc\u03b3RIIB-deficient mice

BackgroundPreviously we established an arthritis-prone FcγRIIB-deficient mouse strain (designated KO1). Anti-mouse CD11b mAb (5C6) has been reported to inhibit the recruitment of peripheral CD11b+ myelomonocytic cells from the blood to the inflammatory site. These cells include neutrophils and monocytes, both of which play important roles in the development of arthritis. Here we treated KO1 mice with 5C6 mAb in order to study its effect on arthritis development.MethodsTo evaluate the disease-preventive effect of 5C6, 4-month-old preclinical KO1 mice were divided into three groups: the first treated with 5C6 for 6 months, the second treated with normal rat IgG for 6 months, as a control, and the third left untreated. Arthritis severity and immunological abnormalities were compared among the groups, along with transcriptional levels of several important arthritis-related factors in ankle joints, spleen, and peripheral blood cells.ResultsThe 5C6 treatment ameliorated arthritis in KO1 mice, showing decreases in inflammatory cell infiltration and osteoclast formation. Analysis of transcriptional levels in ankle joints revealed that compared with the two control groups, the 5C6-treated group showed downregulated expression of RANK, RANKL, MCP-1, RANTES, TNFα, and IL-6, and at the same time showed significantly up-regulated expression of the decoy receptor for RANKL, i.e. osteoprotegerin. In addition, the disease suppression was associated with the lower serum levels of autoantibodies, and the decreased frequencies of activated B cells and plasma cells. The expression levels of B cell activation/differentiation-related cytokines were suppressed in spleen and peripheral leukocytes of the 5C6-treated mice. Intriguingly, while untreated KO1 mice spontaneously developed marked monocytosis, the 5C6-treated mice showed the significantly down-regulated frequency of monocytes.ConclusionsThe outcome of 5C6 treatment was complex, in which the 5C6-mediated disease-preventive effect is likely due on one hand to the decrease in the recruitment of inflammatory cells and osteoclast precursor monocytes from the periphery into the joints, and on the other hand to the suppression of B cell activation/maturation and of autoantibody production via the suppression of B cell stimulating cytokine production. The lower levels of these cytokines may be the secondary effect of the lower frequency of monocytes, since monocytes/macrophages are the major producers of these cytokines.

Anti-Alpha-Tropomyosin Antibody Levels Negatively Correlated with Risk Factors of TC and LDL in Patients with Coronary Heart Disease

Background and objective: Autoantibodies have been implicated in the pathogenesis of coronary heart disease (CHD) since they augment autoimmune activation. We identified novel specific autoantigens and analyzed the correlation between serum autoantibody levels and CHD risk indicators in this study. Methods: Firstly, clinical data and sera from CHD patients were collected. Then, protein microarrays, containing 37 proteins that represent candidate autoantigens, were developed. These arrays were used to profile autoantibodies in randomly selected sera from 35 samples (20 CHD patients and 15 healthy controls). After that, microarrays data were analyzed and differentiable autoantigens for CHD were screened out. Then, ELISA detection were conducted to validate the differentiable autoantigens by using larger numbers of serum samples (131 CHD patients and 131 healthy controls). At last, associations of antibodies with CHD risk indicators parameters were assessed. Findings: Inter-group comparison indicated that three CHD novel autoantigens, including glucose-6-phosphate dehydrogenase (G6PD), alpha-tropomyosin (TPM1) and heterogeneous nuclear ribonucleoprotein D-like (HnRNPDL), was significantly (P < 0.05) increased when compared with the healthy controls. Moreover, significantly IgG autoantibodies increasing of these three autoantigens were confirmed in CHD patients by ELISA (P < 0.0001). Finally, the correction analysis revealed the negative correlation of anti-TPM1 antibody levels and total cholesterol (TC) (P=0.0034), and low-density lipoprotein cholesterol (LDL) (P = 0.0086), respectively. Conclusions: G6PD, TPM1 and HnRNPDL were CHD novel autoantigens and serum anti-TPM1 antibody would be used as a potential marker to predict the risk for CHD patients. Funding: This research has been conducted using the Fundamental Research Funds for the Central public welfare research institutes (ZZ11113). Declaration of Interest: The authors declare no potential, perceived, or real conflict of interest regarding the content of this manuscript. Ethical Approval: All serum samples were collected under institutional review board–approved protocols and after getting the informed consent of the study patients.

WITHDRAWN: Autoimmune response of p53 and its regulator MDM2 in patients with hepatocellular carcinoma

// Li-Ping Dai 1,2,3,* , Ji-Tian Li 3,* , Xiao Wang 1,2,3 and Jian-Ying Zhang 1,2,3 1 Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China 2 Henan Key Laboratory for Tumor Epidemiology, Zhengzhou University, Zhengzhou, Henan, China 3 Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA * Li-Ping Dai and Ji-Tian Li contributed equally to this work Correspondence to: Jian-Ying Zhang, email: jzhang@utep.edu Li-Ping Dai, email: lpdai@zzu.edu.cn Keywords : hepatocellular carcinoma (HCC); autoantibody; MDM2; p53 Received: July 13, 2017&nbsp;&nbsp;&nbsp;&nbsp; Accepted: October 30, 2017&nbsp;&nbsp;&nbsp;&nbsp; Epub: January 03, 2018 Abstract Purpose: The human homologue of the mouse double minute 2 (MDM2) is a transcriptional target and negative regulator of p53. This study aims to investigate the immune response of MDM2 and p53 in hepatocellular carcinoma (HCC). Methods: The autoantibodies were examined by immunoassay in individual sera from 160 HCC patients and 89 normal controls, as well as 76 sequential serum samples from an independent group of 16 HCC patients. The receiver operating characteristic (ROC) analysis was conducted for autoantibody for the distinguishing of HCC from controls. Results: Anti-MDM2 and anti-p53 autoantibodies could distinguish HCC patients from normal individuals in derivation set with area under curve (AUC) of 0.752 and 0.844, as well as in validation set with AUC of 0.658 and 0.703, respectively. The frequencies of anti-MDM2 (30.3%) and anti-p53 (32.9%) autoantibodies were significantly higher in HCC patients than that in normal individuals (10.1%). When anti-MDM2 and anti-p53 autoantibodies combined together, the positive frequency in HCC patients increased to 44.7% which was still significantly higher than that in normal individuals (18.0%). By using longitudinal preclinical samples, 62.5% of patients were observed with anti-MDM2 or anti-p53 autoantibody positive one year prior to diagnosis of HCC. Serum level of autoantibodies against these two TAAs were positively associated with each other ( r = 0.500, P &lt; 0.001). Conclusions: MDM2 and p53 are autoantigens that elicit autoimmune responses in HCC and can be the potential biomarkers for the early detection or predictor of HCC.

Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome.

No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs. Our iPSC-MSCs inhibited the onset of lymphocyte infiltration into salivary glands in the NOD mouse model of SS in the same way as BM-MSCs. Extracellular vesicles (EVs) carry bioactive molecules in the same way as their originating cells and are more stable and considered much safer than cells for therapies. We found that EVs derived from BM-MSCs and iPSC-MSCs suppressed activation of immune cells and expression of proinflammation factors essential for SS progression in vitro and that infusion of iPSC-MSC EVs at the predisease stage decreased the lymphocyte infiltration in salivary glands and serum autoantibody levels in the same way as infusion of BM-MSCs and iPSC-MSCs. These data suggested that iPSC-MSC EVs have the potential to prevent the progression of SS before the onset of sialadenitis.

Diagnostic value of α-enolase expression and serum α-enolase autoantibody levels in lung cancer.

ABSTRACTObjective:To investigate the diagnostic value of α-enolase (ENO1) and serum ENO1 autoantibody levels in lung cancer. Methods:Immunohistochemistry staining and ELISA were performed to detect ENO1 expression in lung tissue and serum ENO1 autoantibody levels, respectively. Results:The expression of ENO1 was higher in lung cancer tissues than in benign lung disease tissues (p < 0.001). The proportion of lung cancer samples expressing ENO1 was not significantly different among the various pathological classification groups. The proportion of samples expressing ENO1 was higher in lung cancer patients in stages I/II than in those in stages III/IV (ℳ2 = 5.445; p = 0.018). The expression of ENO1 in lung cancer tissues was not associated with age, gender, or smoking history. Serum ENO1 antibody levels were significantly higher in the lung cancer group than in the benign lung disease and control groups (p < 0.001). The differences among the pathological classification groups were not statistically significant. Serum ENO1 antibody levels were also in lung cancer patients in stages I/II than in those in stages III/IV (p < 0.01). Serum ENO1 antibody levels were not associated with age, gender, or smoking history in lung cancer patients. The ROC curve representing the diagnosis of lung cancer based on ENO1 antibody levels had an area under the curve of 0.806. Conclusions:Our results suggest that high levels of ENO1 are associated with the clinical stage of lung cancer and that ENO1 expression and its serum autoantibody levels show diagnostic value in lung cancer.