• IMMUNE NETWORK
• /
• 제21권5호
• /
• pp.34.1-34.16
• /
• 2021

Sjögren's syndrome (SS) is an autoimmune disease characterized by dryness of the mouth and eyes. The glandular dysfunction in SS involves not only T cell-mediated destruction of the glands but also autoantibodies against the type 3 muscarinic acetylcholine receptor or aquaporin 5 (AQP5) that interfere with the secretion process. Studies on the breakage of tolerance and induction of autoantibodies to these autoantigens could benefit SS patients. To break tolerance, we utilized a PmE-L peptide derived from the AQP5-homologous aquaporin of Prevotella melaninogenica (PmAqp) that contained both a B cell "E" epitope and a T cell epitope. Repeated subcutaneous immunization of C57BL/6 mice with the PmE-L peptide efficiently induced the production of Abs against the "E" epitope of mouse/human AQP5 (AQP5E), and we aimed to characterize the antigen specificity, the sequences of AQP5E-specific B cell receptors, and salivary gland phenotypes of these mice. Sera containing anti-AQP5E IgG not only stained mouse Aqp5 expressed in the submandibular glands but also detected PmApq and PmE-L by immunoblotting, suggesting molecular mimicry. Characterization of the AQP5E-specific autoantibodies selected from the screening of phage display Ab libraries and mapping of the B cell receptor repertoires revealed that the AQP5E-specific B cells acquired the ability to bind to the Ag through cumulative somatic hypermutation. Importantly, animals with anti-AQP5E Abs had decreased salivary flow rates without immune cell infiltration into the salivary glands. This model will be useful for investigating the role of anti-AQP5 autoantibodies in glandular dysfunction in SS and testing new therapeutics targeting autoantibody production.

• Clinical and Experimental Pediatrics
• /
• 제53권3호
• /
• pp.414-419
• /
• 2010

목 적 : 제 1형 당뇨병에서 보이는 자가 항체와 질환의 진행에 따른 변화와의 관계는 여러 연구에서 보고되었고, 항체가가 높을수록 진행의 정도가 급격하였다. 따라서 진단 당시에 시행한 자가 항체의 발현 여부에 따라 임상 발현 정도가 다를 것으로 생각하여, 자가 항체 유무에 따라 임상 양상과 검사 소견의 차이가 있는지를 확인하고자 하였다. 방 법 : 1999년 4월부터 2008년 3월까지 3개 대학병원에 내원하여 제 1형 당뇨병으로 진단받은 18세 미만 환자 중 처음 진단 당시에 췌장 자가 항체인 GADA 혹은 IAA의 검사를 시행하였던 96명에서 진단 당시 시행한 혈액 검사 및 임상 양상을 항체 그룹에 따라 나누어 비교 분석하였다. 결 과 : GADA는 87명의 환자에서 검사가 이루어 졌고, 이 중 48명(55.2%)에서 양성을 보였다. IAA는 88명 중 35명(39.8%)이 양성을 보였다. 두가지 항체를 모두 검사한 환자는 83명이었고, 이 중 22.8%에서 두 항체가 모두 검출되었고, 38.6%에서는 모두 음성을 보였다. 1가지 이상의 항체를 갖는 환자군에서는 음성군에 비해 비교적 어린 나이에 당뇨병이 발생하였고, 낮은 BMI, 낮은 혈청 교정 Na 수치 및 낮은 혈청 오스몰농도를 보였다(P <0.05). 자가 항체 중 GADA 양성군과 음성군 사이의 검사소견 상에서도 같은 차이를 보였다. 그러나 IAA 항체 유무에 따른 비교에서는 발생 연령이외는 두 군사이에 임상 및 검사소견상 유의한 차이를 볼 수 없었다. 결 론 : 항체 양성군과 음성군 사이에서 보이는 대사적 결과의 차이는 비교적 적었으나 GADA와 IAA 항체의 양성율은 어린 연령에서 높았다. 따라서 비교적 어린 연령에 발생하는 1형 당뇨병에서는 질환을 처음으로 진단할 때자가 항체 유무를 확인하고, 만약 항체가 확인되면 향후 집중적인 인슐린 치료를 시행하여 보다 좋은 예후를 유도하는데 도움이 될 수 있을 것이다.

• Clinical and Experimental Pediatrics
• /
• 제48권1호
• /
• pp.85-87
• /
• 2005

저자들은 피부 병변과 간기능 이상이 동반된 신생아 루푸스 1례를 경험하여 보고하는 바이다.

• BMB Reports
• /
• 제39권2호
• /
• pp.189-196
• /
• 2006

Alterations in the amino acid structure or sequence can generate neo-epitopes from self-proteins causing autoaggressive immune attack. Reactive nitrogen species are an important factor that induces post-translational modification of proteins by cellular reduction and oxidation mechanism; cysteinyl-nitrosylation or tyrosine nitration leading to potentially pathogenic pathways. It was thought of interest to investigate the immunogenicity of nitrated poly L-tyrosine vis-$\`{a}$-vis its possible role in the induction of antibodies in systemic lupus erythematosus (SLE). Commercially available poly L-tyrosine was exposed to nitrating species and the damage was monitored by UV spectroscopy and alkaline gel electrophoresis. The results indicated the formation of 3-nitrotyrosine. Nitrated poly L-tyrosine induced higher titre antibodies as compared to the native form. Nitrated poly L-tyrosine was recognized by the autoantibodies present in the sera of patients suffering from SLE by enzyme immunoassays and band shift assay. The possible role of nitrated self-proteins has been discussed in the production of circulating anti-DNA antibodies in SLE.

• 한국가축번식학회지
• /
• 제15권3호
• /
• pp.225-231
• /
• 1991

These experiments were carried out ot detect autoantiboies to zona pellucida in sera from infertile women using indirect ELISA and IFA and to investigate their effect on in vitro fertilization of mouse ova. In inidirect ELISA test, 12 of 116(10.3%) serum samples form infertile women gave positive reaction whereas all of 16 samples from fertile women and men were negative. Furthermore, in indirect IFA test, 17 of 116 (14.7%) serum samples from infertile women gave positive fluorescence whereas all of control sera were negative fluorescence. The fertilization rates(15.9%) of mouse eggs treated with positive sera were significantly lower than those(51.9%＋71.2%) autoantibodies to zonapellucida are responsible for infertility in unexplained infertile women, presumably by perventing sperm attachment and penetration.

• Childhood Kidney Diseases
• /
• 제24권2호
• /
• pp.138-142
• /
• 2020

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare and life-threatening disorder. Typical HUS is often caused by Shiga toxin-positive Escherichia coli, while aHUS is caused by dysregulation of the alternative pathway of the complement system in association with genetic abnormalities or development of autoantibodies. Eculizumab, a humanized anti-complement 5 monoclonal antibody, is recommended for the treatment of aHUS, but its long-term safety and efficacy in pediatric patients remain under review. In this paper, we report a pediatric case of aHUS with anti-complement factor H autoantibodies, who was treated successfully with eculizumab.

• Journal of Genetic Medicine
• /
• 제18권2호
• /
• pp.132-136
• /
• 2021

Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant pathogenic variants in one of 14 currently known monogenic genes. Characteristics of patients with MODY include early-onset clinical disease with a family history of diabetes and negative autoantibodies and may present with heterogeneous phenotypes according to the different subtypes. Here, we report a patient with early-onset diabetes who presented asymptomatic mild fasting hyperglycemia with the absence of autoantibodies. She was diagnosed with glucokinase (GCK)-MODY caused by a GCK variant, c.1289T>C (p.L430P), identified by targeted gene-panel testing, and the affected father had the same variant. We interpreted this rare missense variant as a likely pathogenic variant and then she stopped taking oral medication. This case highlights the usefulness of gene-panel testing for accurate diagnosis and appropriate management of MODY. We also note the importance of familial genetic testing and genetic counseling for the proper interpretation of MODY variants.

• 대한임상검사과학회지
• /
• 제54권2호
• /
• pp.163-166
• /
• 2022

Acquired hemophilia A (AHA) is an uncommon autoimmune bleeding disorder in which autoantibodies that affect the functions of factor VIII (FVIII) are present in the blood. The initial diagnosis of AHA is difficult as the presentations of AHA differ from those of congenital hemophilia A. Moreover, the treatment of AHA is more complex due to the presence of autoantibodies against FVIII. Here, we present a case report of postpartum AHA, to increase the perception and knowledge regarding the recognition and management of such cases. We present a young female with the chief complaint of vaginal bleeding and upper arm ecchymosis. Laboratory results exhibited isolated prolonged activated partial thromboplastin time (APTT) and FVIII inhibitors. The patient was treated with corticosteroids, FVIII concentrates, and a bypassing agent. In conclusion, unexplained postpartum bleeding, unmanageable with basic hemostatic measures, should lead to clinical suspicion of an acquired bleeding disease.

• IMMUNE NETWORK
• /
• 제16권4호
• /
• pp.219-232
• /
• 2016

Production of high affinity antibodies for antigens is a critical component for the immune system to fight off infectious pathogens. However, it could be detrimental to our body when the antigens that B cells recognize are of self-origin. Follicular helper T, or Tfh, cells are required for the generation of germinal center reactions, where high affinity antibody-producing B cells and memory B cells predominantly develop. As such, Tfh cells are considered as targets to prevent B cells from producing high affinity antibodies against self-antigens, when high affinity autoantibodies are responsible for immunopathologies in autoimmune disorders. This review article provides an overview of current understanding of Tfh cells and discusses it in the context of animal models of autoimmune diseases and allograft rejections for generation of novel therapeutic interventions.

• Clinical and Experimental Reproductive Medicine
• /
• 제31권3호
• /
• pp.149-154
• /
• 2004

Objective: To assess the association with autoimmune endocrine diseases and detection rate of autoimmune antibodies and its clinical significance in patients with premature ovarian failure. Methods: Twenty eight patients with primary or secondary amenorrhea manifesting hormonal and clinical features of premature ovarian failure (primary POF: 7, secondary POF: 21) were investigated. We tested them TFT, 75 g OGTT, ACTH and S-cortisol for thyroiditis, IDDM, Addison's disease, and antithyoglobulin antibody, antimicrosomal antibody, antinuclear antibody, rheumatic factor, anti-smooth muscle antibody, anti-acetylcholine receptor antibody for non-organ specific autoimmune disorders. Results: Only one patient was diagnosed as IDDM and no patients had abnormal TFT or adrenal function test. More than one kind of autoantibody was detected in 11 patients of all (39.2%): 5 patients (71.4%) of primary POF group and 6 patients (21.4%) of secondary POF group. Eleven patients (39.3%) had antithyroglobulin antibody, 4 (14.3%) had antimicrosomal antibody, 2 (7.1%) had antinuclear antibody, 2 (7.1%) had rheumatic factor, 1 (3.6%) had anti-smooth muscle antibody, 1 (3.6%) had anti-acetylcholine receptor antibody. Conclusions: Premature ovarian failure may occur as a component of an autoimmune polyglandular syndrome, so patients should be measured with free thyroxine, thyroid-stimulating hormone, fasting glucose and electrolytes. Measurement of thyroid autoantibodies in POF patients may be important in identifying patients at risk of developing overt hypothyoidism, but other autoantibodies may not be suitable for screening test.