• Clinical and Experimental Pediatrics
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• v.58 no.7
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• pp.267-269
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• 2015

Antithymocyte globulin (ATG) is used as an immunosuppressive treatment (IST) to deplete clonal suppressor T cells in patients with severe aplastic anemia (SAA). The depletion of suppressor T cells by ATG may affect the activation of B cells, which results in an increased risk for autoimmune conditions. A 12-year-old boy was diagnosed with idiopathic SAA. As he did not have an human leukocyte antigen-matched sibling, he was treated with rabbit ATG (3.5 mg/kg/day for 5 days) and cyclosporine. Five months later, he became transfusion independent. However, 23 months after IST, he complained of mild hand tremors, sweating, weight loss, palpitations, and goiter. Results of thyroid function tests revealed hyperthyroidism (free thyroxine, 3.42 ng/dL; thyroid stimulating hormone [TSH], <0.01 nIU/mL; triiodothyronine, 3.99 ng/mL). Results of tests for autoantibodies were positive for the antimicrosome antibody and TSH-binding inhibitory immunoglobulin, but negative for the antithyroglobulin antibody and antinuclear antibody. He was treated with methimazole, and his symptoms improved. The patient has been disease free for 39 months after IST and 9 months after methimazole treatment. This case report suggests that although rare, rabbit ATG may have implications in the pathogenesis of autoimmune hyperthyroidism. Our findings suggest that thyroid function tests should be incorporated in the routine follow-up of SAA patients treated with ATG.

• Clinical and Experimental Pediatrics
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• v.59 no.10
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• pp.421-424
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• 2016

Recurrent macrophage activation syndrome (MAS) is very rare. We present the case of an adolescent boy with human leukocyte antigen (HLA) B27-positive ankylosing spondylitis (AS), who experienced episodes of recurrent MAS since he was a toddler. A 16-year-old boy was admitted because of remittent fever with pancytopenia and splenomegaly after surgical intervention for an intractable perianal abscess. He had been diagnosed with hemophagocytic lymphohistiocytosis (HLH) 4 different times, which was well controlled with intravenous immunoglobulin and steroids since the age of 3. We were unable to identify the cause for the HLH. He remained symptom-free until the development of back pain and right ankle joint pain with swelling at 15 years of age. He was diagnosed with HLA B27-positive AS with bilateral active sacroiliitis. He showed symptom aggravation despite taking naproxen and methotrexate, and the symptoms improved with etanercept. On admission, his laboratory data showed leukopenia with high ferritin and triglyceride levels. Bone marrow biopsy examination showed histiocytic hyperplasia with hemophagocytosis. There was no evidence of infection. He received naproxen alone, and his symptoms and laboratory data improved without any other immunomodulatory medications. Genetic study revealed no primary HLH or inflammasome abnormalities. In this case, underlying autoimmune disease should have been considered as the cause of recurrent MAS in the young patient once primary HLH was excluded.

• 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.

• Journal of Animal Science and Technology
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• v.52 no.6
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• pp.451-457
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• 2010

The porcine MHC (Major Histocompatibility Complex), encoding the SLA (Swine Leukocyte Antigen) genes, is one of the most significant regions associated with immune rejection in relation to transplantation. In this study, three SLA class I (SLA-1, SLA-3, SLA-2) loci and three SLA class II (DRB1, DQB1, DQA) loci were investigated in the previously unidentified Korean native pig (KNP) population that was closely inbred in the Livestock Technology Research Station in Cheongyang, Korea. Total thirteen KNPs from four generations were genotyped for the SLA alleles and haplotypes were investigated using PCR-SSP (Sequence-Specific Primer) method. The results showed that all of these KNPs had Lr-56.30/56.30 homozygous haplotype, indicating high level of inbreeding in the SLA genes. The inbreeding status of these animals was also investigated using microsatellite (MS) markers. From the 50 MS markers investigated, 17 MS markers were fixed in all generations and the fixed alleles are increased as 26 loci for the fourth generation. Two MS markers, S0069 and SW173, were heterozygous for all the animals tested. Observed and expected heterozygosities were calculated and the average inbreeding coefficients for each generation were also calculated. In the fourth generation, the average inbreeding coefficients was 0.732 and this may increase with further inbreeding process. Analysis of the SLA haplotypes and MS alleles can give important information for breeding the pigs for xenotransplantation studies.

• Journal of Obesity & Metabolic Syndrome
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• v.27 no.4
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• pp.233-237
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• 2018

Background: Obesity is a complex, medical condition causally contributing to many chronic diseases and a number of efforts have been made to find the associated markers for novel prevention and treatment of obesity. Our study was to evaluate the relationship between gut immune response and obesity and overweight with use of fecal calprotectin (FC) both in adult and children groups. Methods: Fecal samples were obtained from 74 subjects: 14 non-obese and overweight children (PN), 13 obese and overweight children (PO), 20 non-obese and overweight adults (AN), and 27 obese and overweight adults (AO). FC was measured using a commercial Legend Max quantitative enzyme-linked immunosorbent assay (BioLegend). Mann-Whitney U-test was used for statistical analysis. Results: Median FC concentration was $7.9{\mu}g/g$ (range, $1.9-28.9{\mu}g/g$) for PN, $5.0{\mu}g/g$ (range, $2.6-29.6{\mu}g/g$) for PO, $9.5{\mu}g/g$ (range, $0.8-28.9{\mu}g/g$) for AN, and $10.0{\mu}g/g$ (range, $1.6-25.6{\mu}g/g$) for AO, respectively. In both adults and children age groups, the FC showed no statistically significant difference between AO and AN or PO and PN. However, FC showed statistically significant difference (P<0.05) between AO and PO while not significant between AN and PN. Conclusion: FC level in AO was significantly higher than that in PO, suggestive of different pathophysiologic mechanism between children obesity and adults obesity.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.771-779
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• 2018

BACKGROUND: Mesenchymal stromal cells (MSCs) are multipotent stem cells that can differentiate into several cell types. In addition, many studies have shown that MSCs modulate the immune response. However, little information is currently available regarding the maintenance of immunomodulatory characteristics of MSCs through passages. Therefore, we investigated and compared cytokine and gene expression levels from adipose (AD) and bone marrow (BM)-derived MSCs relevant to immune modulation from early to late passages. METHODS: MSC immunophenotype, growth characteristics, cytokine expressions, and gene expressions were analyzed. RESULTS: AD-MSCs and BM-MSCs had similar cell morphologies and surface marker expressions from passage 4 to passage 10. Cytokines secreted by AD-MSCs and BM-MSCs were similar from early to late passages. AD-MSCs and BM-MSCs showed similar immunomodulatory properties in terms of cytokine secretion levels. However, the gene expressions of tumor necrosis factor-stimulated gene (TSG)-6 and human leukocyte antigen (HLA)-G were decreased and gene expressions of galectin-1 and -3 were increased in both AD- and BM-MSCs with repeated passages. CONCLUSION: Our study showed that the immunophenotype and expression of immunomodulation-related cytokines of AD-MSCs and BM-MSCs immunomodulation through the passages were not significantly different, even though the gene expressions of both MSCs were different.

• Journal of Genetic Medicine
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• v.17 no.2
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• pp.68-72
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• 2020

Purpose: Trisomy 21, the cause of Down syndrome (DS) with various medical problems, is the most common aneuploidy during the fetal period. For diagnosis, a non-invasive screening test using maternal blood, which cannot be confirmed and invasive confirmation test with a risk of miscarriage, may be performed. The trophoblast retrieval and isolation of the cervix (TRIC) have been proposed by some researchers as an alternative to overcome the limitations of current tests. We experimented using TRIC to identify the possibility of trisomy 21 for the first time in Asia. Materials and Methods: Three cases of DS were analyzed confirmed by invasive tests (chorionic villus sampling, amniocentesis). All samples of trophoblasts immediately were immersed in phosphate-buffered saline and processed with formalin for fixation. The trophoblasts were isolated using an anti-human leukocyte antigen-G antibody coupled to magnetic nanoparticles. β-human chorionic gonadotropin (hCG)-expressing cells were considered as trophoblast cells, and the detection rate calculated. DS was confirmed by fluorescence in situ hybridization (FISH). Results: The mean trophoblast detection rate using β-hCG was 78.1%, and the detection rate using FISH was 22.2%. In all cases, the trisomy of chromosome 21 was identified. Conclusion: Trophoblast can be obtained from the five weeks of gestation and has a high detection rate, so it is noted that it can replace the current prenatal genetic test. To realize the clinical application as a prenatal genetic test, we will need additional efforts to identify trisomy 21 as well as other chromosomal abnormalities in future large-scale studies.

• Archives of Plastic Surgery
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• v.48 no.6
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• pp.703-713
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• 2021

The field of vascularized composite allografts (VCAs) has undergone significant advancement in recent decades, and VCAs are increasingly common and accepted in the clinical setting, bringing hope of functional recovery to patients with debilitating injuries. A major obstacle facing the widespread application of VCAs is the side effect profile associated with the current immunosuppressive regimen, which can cause a wide array of complications such as infection, malignancy, and even death. Significant concerns remain regarding whether the treatment outweighs the risk. The potential solution to this dilemma would be achieving VCA tolerance, which would allow recipients to receive allografts without significant immunosuppression and its sequelae. Promising tolerance protocols are being studied in kidney transplantation; four major trials have attempted to withdraw immunosuppressive treatment with various successes. The common theme in all four trials is the use of radiation treatment and donor cell transplantation. The knowledge gained from these trials can provide valuable insight into the development of a VCA tolerance protocol. Despite similarities, VCAs present additional barriers compared to kidney allografts regarding tolerance induction. VCA donors are likely to be deceased, which limits the time for significant pre-conditioning. VCA donors are also more likely to be human leukocyte antigen-mismatched, which means that tolerance must be induced across major immunological barriers. This review also explores adjunct therapies studied in large animal models that could be the missing element in establishing a safe and stable tolerance induction method.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.5
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• pp.396-405
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• 2022

Purpose: This study evaluated the predictive role of fecal calprotectin (FC) measured at an early stage of treatment for monitoring clinical remission (CR) after six months and endoscopic remission (ER) after one year of treatment in pediatric Crohn's disease (CD). Methods: This retrospective study included 45 patients who simultaneously underwent ileocolonoscopy and FC testing during follow-up. FC levels were measured before and after six weeks of treatment. CR was assessed after six months of treatment using Pediatric Crohn' s Disease Activity Index and acute-phase reactants. ER was assessed after one year using the Simple Endoscopic Score for Crohn's Disease. Results: Twenty-nine (64.4%) patients used oral prednisolone for remission induction and 16 (35.6%) patients used anti-tumor necrosis factor-alpha. Thirty (66.7%) patients achieved CR, while 24 (53.3%) achieved ER. The FC level measured after six weeks of treatment could predict CR (χ²=9.15, p=0.0025) and ER (χ²=12.31, p=0.0004). The δFC could predict CR (χ²=7.91, p=0.0049), but not ER (χ²=1.85, p=0.1738). With a threshold of ≤950.4 ㎍/g, FC at week six could predict CR with 76.7% sensitivity and 73.3% specificity. The area under the curve (AUC) was 0.769 (standard error 0.0773, p=0.0005). The same threshold predicted ER with 87.5% sensitivity and 71.4% specificity. The AUC was 0.774 (standard error 0.074, p=0.0002). Conclusion: FC assay at an early stage of treatment can be used as a surrogate marker to predict CR and mucosal healing in pediatric CD.

• Clinical and Experimental Vaccine Research
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• v.12 no.4
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• pp.328-336
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• 2023

Purpose: Human peripheral blood mononuclear cell (PBMC)-based in vitro systems can be of great value in the development and assessment of vaccines but require the right medium for optimal performance of the different cell types present. Here, we compare three commonly used media for their capacity to support innate and adaptive immune responses evoked in PBMCs by Toll-like receptor (TLR) ligands and whole inactivated virus (WIV) influenza vaccine. Materials and Methods: Human PBMCs were cultured for different periods of time in Roswell Park Memorial Institute (RPMI), Dulbecco's minimal essential medium (DMEM), or Iscove's modified DMEM (IMDM) supplemented with 10% fetal calf serum. The viability of the cells was monitored and their responses to TLR ligands and WIV were assessed. Results: With increasing days of incubation, the viability of PBMCs cultured in RPMI or IMDM was slightly higher than that of cells cultured in DMEM. Upon exposure of the PBMCs to TLR ligands and WIV, RPMI was superior to the other two media in terms of supporting the expression of genes related to innate immunity, such as the TLR adaptor protein gene MyD88 (myeloid differentiation factor 88), the interferon (IFN)-stimulated genes MxA (myxovirus resistance protein 1) and ISG56 (interferon-stimulated gene 56), and the leukocyte recruitment chemokine gene MCP1 (monocyte chemoattractant protein-1). RPMI also performed best with regard to the activation of antigen-presenting cells. As for adaptive immunity, when stimulated with WIV, PBMCs cultured in RPMI or IMDM contained higher numbers of IFNγ-producing T cells and secreted more immunoglobulin G than PBMCs cultured in DMEM. Conclusion: Taken together, among the different media assessed, RPMI was identified as the optimal medium for a human PBMC-based in vitro vaccine evaluation system.