• Genomics & Informatics
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• v.13 no.4
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• pp.126-131
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• 2015

Fulminant type 1 diabetes (T1DM) is a distinct subtype of T1DM that is characterized by rapid onset hyperglycemia, ketoacidosis, absolute insulin deficiency, and near normal levels of glycated hemoglobin at initial presentation. Although it has been reported that class II human leukocyte antigen (HLA) genotype is associated with fulminant T1DM, the genetic predisposition is not fully understood. In this study we investigated the HLA genotype and haplotype in 11 Korean cases of fulminant T1DM using imputation of whole exome sequencing data and compared its frequencies with 413 participants of the Korean Reference Panel. The $HLA-DRB1^*04:05-HLA-DQB1^*04:01$ haplotype was significantly associated with increased risk of fulminant T1DM in Fisher's exact test (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.56 to 10.86; p = 0.009). A histidine residue at $HLA-DR{\beta}1$ position 13 was marginally associated with increased risk of fulminant T1DM (OR, 2.45; 95% CI, 1.01 to 5.94; p = 0.054). Although we had limited statistical power, we provide evidence that HLA haplotype and amino acid change can be a genetic risk factor of fulminant T1DM in Koreans. Further large-scale research is required to confirm these findings.

• Molecules and Cells
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• v.20 no.3
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• pp.339-347
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• 2005

IL-17 (IL-17A or CTLA-8) is the founding member of a novel family of inflammatory cytokines, and emerging evidence indicates that it plays a central role in inflammation and autoimmunity. IL-17 is made primarily, if not exclusively by T cells, but relatively little is known about how its expression is regulated. In the present study, we examined the requirements and mechanisms for IL-17 expression in primary mouse lymphocytes. Like many cytokines, IL-17 is induced rapidly in primary T cells after stimulation of the T cell receptor (TCR) through CD3 crossinking. Surprisingly, however, the pattern of regulation of IL-17 is different in mice than in humans, because "costimulation" of T cells through CD28 only mildly enhanced IL-17 expression, whereas levels of IL-2 were dramatically enhanced. Similarly, several other costimulatory molecules such as ICOS, 4-1BB and CD40L exerted only very weak enhancing effects on IL-17 production. In agreement with other reports, IL-23 enhanced CD3-induced IL-17 expression. However, IL-17 production can occur autonomously in T cells, as neither dendritic cells nor IL-23 were necessary for promoting short-term production of IL-17. Finally, to begin to characterize the TCR-mediated signaling pathway(s) required for IL-17 production, we showed that IL-17 expression is sensitive to cyclosporin-A and MAPK inhibitors, suggesting the involvement of the calcineurin/NFAT and MAPK signaling pathways.

• Tuberculosis and Respiratory Diseases
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• v.67 no.3
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• pp.234-238
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• 2009

Henoch-$Sch\ddot{o}nlein$ Purpura (HSP) is a systemic vasculitis involving small vessels with the deposition of immune complexes containing IgA and C3, which is characterized by associated skin, joint, renal, and gastrointestinal manifestations. Although there were several causes such as autoimmunity, infection, and drugs, it also can be presented as a form of vasculitidies associated with malignancies. We report a case of HSP developed during treatment for non-small cell lung cancer in a 66-year-old man. Multiple purpuric skin lesions occurred in both legs after the first cycle of chemotherapy, which was diagnosed as HSP by clinical and pathologic examinations. Due to the itching sensation, topical steroid was applied and the patient was improved 3 weeks later without a scheduled change in chemotherapy.

• Korean Journal of Biological Psychiatry
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• v.3 no.1
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• pp.109-114
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• 1996

We have previously reported that Korean schizophrenic patients hove low production of IL-2 in vitro suggestive of autoimmunity to the pathogenesis of the disorder. In an attempt to further explore this issue, we measured in vivo serum levels of interleukins(IL-$1{\beta}$, IL-2, and IL-6) using a quantitative "sandwich" enzyme immunoassay(ELISA) in 26 male schizophrenic patients and in 26 age-matched normal controls. Patients met DSM-IV criteria for schizophrenia and were drug free for at least six months. The severity of symptoms was assessed by SANS and SAPS. We found a significant increase of IL-2 level(p<0.05) in schizophrenic patients as compared with normal controls. There were significant positive correlations between IL-2, IL-6 levels and negative symptom scores. There were no correlations between age, age at onset, duration of illness and interleukin levels. Our results may support the hypothesis of viral-autoimmune dysfunction in schizophrenia. IL-2 or IL-6 may be associated with specific clinical feature in schizophrenic syndrome, especially negative symptom.

• Clinical and Experimental Reproductive Medicine
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• v.25 no.1
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• pp.17-24
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• 1998

We have previously demonstrated that specific antigens involved in autoimmunity in endometriosis may be endometrial proteins with molecular weight (mw) of 71, 92, and 103 kilodalton (kDa). The purposes of this study were to determine the incidence of IgG antibodies against these endometrial antigens in peritoneal fluid of patients with endometriosis and to evaluate the antigenic differences between the endometria of patients with and without endometriosis. Forty peritoneal fluid (PF) from 24 patients with endometriosis and 16 patients without endometriosis (control patients) were tested against endometrial protein from patients (n=8) with endometriosis and from control patients (n=10) by western blot. Fifteen (62.5%) of 24 PF samples from patients with endometriosis had specific Immunoglobuiin (Ig) G antibodies against one of three endometrial proteins with mw of 71, 92 and 103 kDa but none of PF samples from control patients had these antibodies. The electrophoretic pattern of endometrial proteins from patients with endometriosis was similiar to that from control patients. Furthemore there was no significant difference in specific PF Immunoglobulin G binding to endometrial proteins regardless of origin of these proteins. Our data indicate that specific humoral immune response can be found in PF of patients with endometriosis and that specific antigens inducing this immune response are present in human endometrium and that there is no antigenic difference between the endometria of patients with and without endometriosis.

• Journal of Life Science
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• v.20 no.5
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• pp.670-675
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• 2010

Autoimmune regulator gene (Aire) is expressed in the thymus and controls the expression of peripheral self-antigens, known as promiscuous genes. Aire and promiscuous genes are involved in T cell tolerance and autoimmunity in the thymus. Here, we identified Aire-expressing fibroblastic reticular cell (FRC), which was derived from mouse lymph node and also expressed in insulin promiscuous antigen. The expression of insulin was increased in cultured FRC over-expressed with Aire. These data suggest that Aire regulates promiscuous gene expression in FRC, and that this function might be under peripheral selection control.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.463-468
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• 2012

Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic ${\beta}$-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic ${\beta}$-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic ${\beta}$-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic ${\beta}$-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic ${\beta}$ cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.

• Kosin Medical Journal
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• v.33 no.3
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• pp.307-317
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• 2018

Background: Detection of antibodies to extractable nuclear antigens (ENAs) is needed for the diagnosis in systemic autoimmune diseases. In this study, we compared three reagents using line immunoblot assay (LIA) or multiplex bead immunoassay for detecting the anti-ENAs. Methods: A total of 89 sera were tested by 3 different assays: EUROASSAY Anti-ENA Profile (Euroimmune, Germany), Polycheck Autoimmune Test (Biocheck GmbH, Germany), and $FIDIS^{TM}$ Connective Profile (Biomedical Diagnostics, France). The following individual ENAs were investigated: Sm, SS-A (Ro), SS-B (La), Scl-70, Jo-1 and RNP. We reviewed medical records to investigate the discrepant results among three methods. Results: Overall percent agreements were 96.1% between EUROASSAY Anti-ENA Profile and $FIDIS^{TM}$ Connective profile; 90.4% between EUROASSAY Anti-ENA Profile and Polycheck Autoimmune Test using the manufacturers' cutoff; 96.4% between EUROASSAY Anti-ENA Profile and Polycheck Autoimmune Test using a upward cutoff; 90.4% between $FIDIS^{TM}$ Connective profile and Polycheck Autoimmune Test the manufacturers' cutoff; and 96.4% between $FIDIS^{TM}$ Connective profile and Polycheck Autoimmune Test a upward cutoff. Conclusions: The three assays showed excellent agreement with each other. With appropriate cutoff, the all three assays for six of the anti-ENA tests investigated in this study can be used in clinical laboratories for detecting the anti-ENAs.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.1
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• pp.133-144
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• 2022

The objective was to propose effectiveness of conservative treatments including Korean medical treatments for symptomatic Schmorl's nodes (SNs). We conducted retrospective study that analyzed the medical records of two patients with the symptomatic SNs. They were treated by conservative treatments including Korean medical treatments for 3 weeks. We evaluated numeric rating scale (NRS), Oswestry disability index (ODI) and EuroQol-5 dimension (EQ-5D) index. After treatment, NRS, ODI were decreased and EQ-5D index was increased. We performed literature search to analyze the mechanisms of its treatment and evaluate clinical trials. There were three major mechanisms: (1) Improving constructive stability of vertebrae, (2) alleviating pain, and (3) controlling autoimmunity. When comparing operative treatment (OT) trials and conservative treatment (CT) trials, we couldn't find conclusive basis that support which one is more effective. As OT trials reported some severe adverse events, CT trials reported mild adverse events. The conservative treatments that we used encompasses those mechanisms and is relatively safe. To obtain exact evidence of effectiveness, further studies are needed.

• Hanyang Medical Reviews
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• v.33 no.1
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• pp.10-16
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• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.