Detection of Autoantibodies against Aquaporin-1 in the Sera of Patients with Primary Sjögren’s Syndrome

Jehan Alam,최윤식,고정희,곽승기,박성환,송영욱,박경표,최영님 대한면역학회 2017 Immune Network Vol.17 No.2

The pathophysiology of glandular dysfunction in Sjögren’s syndrome (SS) has not been fully elucidated. Previously, we reported the presence of autoantibodies to AQP-5 in patients with SS, which was associated with a low resting salivary flow. The purpose of this study was to investigate the presence of anti-AQP1 autoantibodies. To detect anti-AQP1 autoantibodies, cell-based indirect immunofluorescence assay was developed using MDCK cells that overexpressed human AQP1. By screening 112 SS and 52 control sera, anti-AQP1 autoantibodies were detected in 27.7% of the SS but in none of the control sera. Interestingly, the sera that were positive for anti-AQP1 autoantibodies also contained anti-AQP5 autoantibodies in the previous study. Different from anti-AQP5 autoantibodies, the presence of anti-AQP1 autoantibodies was not associated with the salivary flow rate. Although anti-AQP1 autoantibodies are not useful as a diagnostic marker, the presence of autoantibodies to AQP1 may be an obstacle to AQP1 gene therapy for SS.

Identification of Medium-Length Antineurofilament Autoantibodies in Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis

Shisi Wang,Cancan Xu,Xiaobo Sun,Yifan Zhou,Yaqing Shu,Shangzhou Xia,Zhengqi Lu,Wei Qiu,Xiaofen Zhong,Lisheng Peng 대한신경과학회 2020 Journal of Clinical Neurology Vol.16 No.3

Background and Purpose Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe central nervous system disorder mediated by NMDAR antibodies that damages neurons. We investigated the correlation between cytoskeletal autoantibodies and the clinical severity in patients with anti-NMDAR encephalitis. Methods Non-NMDAR autoantibodies were identified by screening matched cerebrospinal fluid (CSF) and the serum samples of 45 consecutive patients with anti-NMDAR encephalitis and 60 healthy individuals against N-methyl-D-aspartate receptor 1-transfected and nontransfected human embryonic kidney 293T cells. Immunocytochemistry was performed to assess antibody binding in rat brain sections and primary cortical neurons. Cell-based assays and Western blotting were applied to identify autoantibodies targeting medium neurofilaments (NFMs). We compared clinical characteristics between patients with NMDAR encephalitis who were positive and negative for anti-NFM-autoantibodies. Results Anti-NFM autoantibodies were detected in both the serum and CSF in one patient (2%) and in the serum only in six patients (13%). No antibodies were detected in the serum of healthy controls (7/45 vs. 0/60, p=0.0016). Four of the seven patients with anti-NFM autoantibodies in serum were children (57%), and three (43%) had abnormalities in brain magnetic resonance imaging. These patients responded well to immunotherapy, and either no significant or only mild disability was observed at the last follow-up. Anti-NMDAR encephalitis did not differ with the presence of anti-NFM autoantibodies. Conclusions Anti-NFM autoantibodies may be present in patients with anti-NMDAR encephalitis, indicating underlying neuronal damage. A large cohort study is warranted to investigate the clinical differences between patients with NMDAR encephalitis according to their anti- NFM antibody status.

수포성 유천포창 및 후천성 수포성 피박리증에서 혈청과 소변 IgG 자가항체의 역가에 관한 연구

박정환,안인숙,이창우 한양대학교 의과대학 2002 한양의대 학술지 Vol.22 No.2

The immunoglobulins can be detected in the urine in normal people without any renal disease. According to recent articles, it is known that autoantibodies of IgG, which share the identical antigenic specificities with the serum autoantibodies, targeting some nuclear antigens and cutaneous basement mambrane zone antignes could be detected in the urine in patients with systemic lupus erythematosus and autoimmune bullous diseases. The author examined the urine for the detection of autoantibodies in patients with autoimmune bullons diseases and compared the titers of IgG autoantibidies in the serum and urine in each patient. Six patients were included in this study. They were 2 patient-guoups of bullous pemphigoid (BP) and epidermolysis bullosa acqusita (EBA). Each group consisted of 3 patients having circulating autoantibodies in the serum. For a semi-quantitation of the IgG autoantibodies in the serum and urine specimens in each group,l the indirect immunofluorescent (IIF) tests were performed. All six patients showed positive results of autoantibidies in serum specimens. In each patient-group, IgG autoantibodies were detected in the urine of all patients at low titers. It appeared that cases with high antibody titers in the sera may deliver more frequent positive findings for the urine autoantibodies. The IIF test of the urine could be tried for a diagnosis of autoimmune bullous diseases in some patients with active autoimmune bullous dermatoses, espacially in cases with certain difficulties in collecting serum samples.

전신성 홍반성 루푸스 환자에서 자가항체 검출을 위한 이중면역확산법, ELISA, Western Blot법의 비교 및 자가항체와 임상양상의 연관에 관한 연구

유창달 ( Chang Dal Yoo ),차훈석 ( Hoon Seok Cha ),김성욱 ( Seong Wook Kang ),이은봉 ( Eun Bong Lee ),백한주 ( Han Joo Baek ),임용성 ( Yong Seong Im ),김현아 ( Hyun A Kim ),신찬수 ( Chan Su Shin ),송영욱 ( Yeong Wook Song ),최강원 대한류마티스학회 1996 대한류마티스학회지 Vol.3 No.2

Objective: To investigate the autoantibody profile and its clinical association in patients with systemic lupus erythematosus. Methods: The frequency and clinical correlation of autoantibodies were studied in 73 patients with systemic lupus erythematosus who have been followed in Seoul National University Hospital. Double immunodiffusion, ELISA and immunoblot were used for the detection of autoantibodies. Results: The frequency of each autoantibody measured by double immunodiffusion was as follows; anti-Ro 53.4%, anti-La 11.0%, anti-Sm 20.5%, anti-U1 RNP 20.5%. The frequency of each autoantibody by ELISA was as follows; anti-Ro 69.9%, anti-La 27.4%, anti-Sm 54.8%, anti-Ul RNP 68.5%, anti-dsDNA 72.6%, anti-cardiolipin 47.2% (IgG 43.1%, igM 15.3%). The frequency of each autoantibody by immunoblot was as follows; anti-Ro 15.1%, anti-La 42.5%, anti-Sm 46.6%, anti-Ul RNP 42.5%. anti-ribosomal P(P0) 27.4%. Anti-Ro was associated with decreased frequency of nephrotic syndrome. Anti-Ul RNP was associated with increased frequency of malar rash, Raynaud phenomenon and decreased frequency of nephritis. Patients with both anti-Ro and anti-La had more frequent serositis than those with anti-Ro only. Patients with both anti-Sm and anti-Ul RNP had less frequent thrombocytopenia than those with anti-Ul RNP only. And patients with anti-Sm and anti-dsDNA had more frequent arthritis than those with only one of both antibodies. There was a positive correlation of autoantibody titers between anti-Ro and anti-La, anti-Sm and anti-Ul RNP, anti-dsDNA and anti-cardiolipin (IgG). Taking the result of immunoblot as a standard, both of double immunodiffusion and ELISA showed low sensitivity but high specficity for anti La. As for anti-Sm and anti-Ul RNP, double immunodiffusion showed low sensitivity but high specificity, whereas ELISA showed high sensitivity but low specificity. Conclusions: In our study, some autoantibodies (anti-Ro, anti-Ul RNP) were associated with certain clinical manifestations while others not. Immunoblot being used as a standard method, ELISA showed higher sensitivity but lower specificity for anti-La, anti-Sm and anti-Ul RNP compared with immunodiffusion. It is recommended that in interpretating the laboratory findings of these autoantibodies these parameters of each method should be considered.

성인 기관지천식 환자들에서 기도상피세포 단백에 대한 자가항체의 IgG 아형 분포

권별 ( Byul Kwon ),신지영 ( Jee Young Shin ),김정은 ( Jeong Eun Kim ),예영민 ( Young Min Ye ),서창희 ( Chang Hee Suh ),박해심 ( Hae Sim Park ),남동호 ( Dong Ho Nahm ) 대한천식알레르기학회 2005 천식 및 알레르기 Vol.25 No.4

Background: A possible involvement of autoimmune response to the against airway mucosa tissue in the pathogenesis of nonatopic asthma has been proposed by the earlier studies. Recently, a cytokeratin 18 protein has been identified as an airway epithelial cell autoantigen recognized by circulating IgG autoantibodies from patients with nonatopic asthma. Objective: In this study, we evaluated an IgG subclass distribution of circulating IgG autoantibodies to airway epithelial cell proteins in the serum samples from adult patients with bronchial asthma. Method: IgG subclass (IgG1, IgG2, IgG3, and IgG4) autoantibodies to airway epithelial cell proteins were detected in serum samples from patients with atopic asthma and patients with nonatopic asthma, and healthy controls by Western blot analysis. Result: Detection rate of IgG1 and IgG4 autoantibodies to cytokeratin 18 protein was significantly higher in patients with nonatopic asthma (3/12; 25%) compared to healthy controls (0/12; 0%) and patients with atopic asthma (0/12; 0%)(Chi-square test; P<0.05). However, there was no significant difference in the detection rate of IgG2 and IgG3 autoantibodies to cytokeratin 18 proteins among the three groups (P>0.05). Conclusion: The predominance of circulating IgG1 and IgG4 autoantibodies to cytokeratin 18 protein in patients with nonatopic asthma suggests a possibility of autoantibody-mediated complement activation and chronic activation of autoantigen-specific Th1 and Th2 cells. (Korean J Asthma Allergy Clin Immunol 2005;25:313-319)

Autologous Serum Skin Test for Autoantibodies Is Associated with Airway Hyperresponsiveness in Patients with Asthma

Jang, An-Soo,Park, Jong-Sook,Lee, June-Hyuk,Park, Sung-Woo,Kim, Do-Jin,Park, Choon-Sik S. Karger AG 2007 Respiration Vol.74 No.3

<P><I>Background:</I> Autoimmune diseases have been implicated as a cause of intrinsic asthma; however, there is little data on the role of autoimmunity in the pathogenesis of asthma. <I>Objective:</I> The purpose of this study was to investigate circulating functional autoantibodies against the high-affinity IgE receptor FcεRI or IgE in patients with asthma. <I>Methods:</I> Twenty-eight patients with asthma and 19 control subjects were included. All subjects were skin tested with autologous serum to assess for the potential presence of receptor FcεRI or IgE autoantibodies. If the serum-induced wheal diameter was 1.5 mm larger than the histamine-induced wheal diameter and that was 3 mm larger than the saline-induced wheal diameter at 30 min, the reaction was defined positive. <I>Results:</I> Of the 47 total subjects (both asthma patients and control subjects), 13 (27.7%) had a positive autologous serum skin test (ASST). Of the 28 asthma patients, 8 (28.6%) were regarded as having autoimmune origin. Autoantibodies against FcεRI or IgE were found in asthma patients, irrespective of atopic status (atopy+ 3/13 vs. atopy- 5/15). The wheal diameter related to ASST was not related to atopy. Asthma patients with ASST-positive results as compared with patients with ASST-negative results exhibited a significant increased airway hyperresponsiveness (PC<SUB>20</SUB> methacholine, 2.70 ± 1.27 vs. 9.08 ± 2.35; p < 0.026). <I>Conclusion:</I> Our data demonstrate that aberrant autoantibodies against the high-affinity IgE receptor FcεRI or IgE are related to airway hyperresponsiveness in patients with asthma.</P><P>Copyright © 2006 S. Karger AG, Basel</P>

Glutamic Acid Decarboxylase Autoantibody Detection by Electrochemiluminescence Assay Identifies Latent Autoimmune Diabetes in Adults with Poor Islet Function

Yuxiao Zhu,Li Qian,Qing Liu,Jing Zou,Ying Zhou,Tao Yang,Gan Huang,Zhiguang Zhou,Yu Liu 대한당뇨병학회 2020 Diabetes and Metabolism Journal Vol.44 No.2

Background: The detection of glutamic acid decarboxylase 65 (GAD65) autoantibodies is essential for the prediction and diagnosis of latent autoimmune diabetes in adults (LADA). The aim of the current study was to compare a newly developed electrochemiluminescence (ECL)-GAD65 antibody assay with the established radiobinding assay, and to explore whether the new assay could be used to define LADA more precisely. Methods: Serum samples were harvested from 141 patients with LADA, 95 with type 1 diabetes mellitus, and 99 with type 2 diabetes mellitus, and tested for GAD65 autoantibodies using both the radiobinding assay and ECL assay. A glutamic acid decarboxylase antibodies (GADA) competition assay was also performed to assess antibody affinity. Furthermore, the clinical features of these patients were compared. Results: Eighty-eight out of 141 serum samples (62.4%) from LADA patients were GAD65 antibody-positive by ECL assay. Compared with ECL-GAD65 antibody-negative patients, ECL-GAD65 antibody-positive patients were leaner (P<0.0001), had poorer β-cell function (P<0.05), and were more likely to have other diabetes-associated autoantibodies. The β-cell function of ECLGAD65 antibody-positive patients was similar to that of type 1 diabetes mellitus patients, whereas ECL-GAD65 antibody-negative patients were more similar to type 2 diabetes mellitus patients. Conclusion: Patients with ECL-GAD65 antibody-negative share a similar phenotype with type 2 diabetes mellitus patients, whereas patients with ECL-GAD65 antibody-positive resemble those with type 1 diabetes mellitus. Thus, the detection of GADA using ECL may help to identify the subtype of LADA.

Detection of Autoantibodies Against Nucleoporin p62 in Sera of Patients With Primary Biliary Cholangitis

Alicja Bauer,Andrzej Habior, 대한진단검사의학회 2019 Annals of Laboratory Medicine Vol.39 No.3

Background: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by specific autoantibodies. We evaluated the prevalence of autoantibodies against nucleoporin p62 (anti-p62) in PBC patients’ sera to determine whether it can be a marker for PBC, in comparison with other immunological and biochemical parameters. We validated the performance of our in-house ELISA technique. Methods: Serum samples were collected from 135 PBC patients. Thirty patients with primary sclerosing cholangitis (PSC) and 30 with autoimmune hepatitis (AIH) were included as pathological controls, and 40 healthy blood donors served as healthy controls. The presence of anti-p62 was determined by an in-house ELISA using a recombinant protein. We calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratio (LR+ and LR-) of our in-house ELISA for diagnosing PBC based on anti-p62. Findings were correlated with biochemical data and survival. Results: Anti-p62 was detected in 32 PBC patients (23.7%). Specificity and PPV of anti-p62 for PBC were 99% and 97%, respectively. The difference between proportions of anti-p62-positive patients and controls was 0.23 (95% confidence interval [CI]: 0.03–0.40; P<0.0001); LR+ and LR- were 23.7 and 0.77, respectively. The presence of anti-p62 was associated with higher levels of bilirubin and alkaline phosphatase (P<0.001). The odds ratio for survival was 2.44 (95% CI: 0.87–6.87; P=0.091). Conclusions: Anti-p62 may be regarded as a significant serological marker of PBC.

Asbestos exposure and autoantibody titers

이은수,김영기,김세영,강동묵 대한직업환경의학회 2020 대한직업환경의학회지 Vol.32 No.-

Background: Asbestos is a well-known hazardous substance that causes occupational and environmental diseases including asbestosis (lung fibrosis). Silica exposure which causes silicosis (another type of lung fibrosis) has long been linked to the development of autoimmune diseases; however, there are few studies on the relationship between asbestos exposure and autoimmune diseases. Methods: A total of 54 individuals who had worked in a former asbestos textile factory underwent autoantibody-related blood tests, chest X-ray imaging, and pulmonary function tests. Based on the job exposure matrix (JEM), the estimated asbestos exposure concentrations were determined, and the presence of asbestosis was determined by chest radiography. Results: Scleroderma (Scl-70) and ribonucleoprotein (RNP) antibodies were significantly lowered in the pleural plaque present group than in the absent group. Additionally, Scl-70, RNP, and Sjögren's syndrome type B (SS-B) antibodies were significantly lowered in the asbestosis present group. When stratifying variables with or without asbestosis, Scl-70, Smith, SS-B, and RNP antibodies decreased in female, crocidolite handling group, and higher estimated asbestos exposure level group. Conclusions: Contrary to our expectations that autoantibody titers would be higher in groups with high asbestos exposure or in the asbestosis group, those with asbestosis showed lower titers. But as our research has some methodological limitations, the lowered titer of autoimmune antibody in our asbestos exposed subjects could not be simply interpreted as a lowered risk of autoimmune diseases. So careful interpreting should be taken when examine autoantibodies to screening or diagnose autoimmune diseases in people with asbestos exposure. In addition, it is necessary to establish relevance of asbestosis and autoantibodies through further studies of larger scale and higher confidence levels.

소아 그레이브스병에서 부신호르몬 및 IgE의 변화

리선희,이훈영,유재홍 충남대학교 의과대학 의학연구소 2003 충남의대잡지 Vol.30 No.1

Graves' disease is a autoimmune thyroid disease. In pathogenesis of Graves' disease, T cell is known as that helps production of thyroid autoantibodies. Endocrine and immune systems are connected and interdependent. Adrenal gland plays an important role in this network and control the balance between serum levels of dehydroepiandrosterone sulfate(DHEAS) and cortisol. The authors evaluated the change of adrenal androgen, cortisol and immunoglobulin E as immune modulators in Graves' disease. From March, 1999 to August, 2002, Serum DHEAS, 24 hour urine free cortisol(F) and IgE and thyroid autoantibodies(TsAb, TBII, AMA, ATA) examined in 22 Graves' patients Serum IgE increased in 41.2% of all patients(97.41±99.07IU/mL). DHEAS was increased in only 5.5% of all patients, and it was decreased or included in normal range in 94.5% of patients(99.3±91.49μg/dL). DHEAS was correlated with ATA(r=0.517).Twenty-four hour urine free cortisol was increased in 72.2% of patients(64.45±47.59μg/dL), but it had no interrelationship with thyroid autoantibodies. Ratio of DHEAS/F had 2.08±2.06, and it had negative correlation with TsAb and TBII, respectively(r=-0.487, r=-0.565). These data demonstrate that there are change of adrenal hormones(DHEAS and cortisol) and IgE, and dis-equilibrium between two adrenal hormones in children with Graves' disease, and Thse might be some relevant to the T cell immune response induction of Graves' disease.