• Molecules and Cells
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• 제42권11호
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• pp.747-754
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• 2019

The incidence of atherosclerosis is higher among patients with several autoimmune diseases such as psoriasis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). It is well documented that innate immune cells including macrophages and dendritic cells sense lipid species such as saturated fatty acids and oxidized low-density lipoprotein and produce pro-inflammatory cytokines and chemokines. However, whether a hyperlipidemic environment also impacts autoimmune T cell responses has been unclear. Among $CD4^+$ T cells, Th17 and follicular helper T (Tfh) cells are known to play pathogenic roles in the development of hyperlipidemia-associated autoimmune diseases. This review gives an overview of the cellular and molecular mechanisms by which dysregulated lipid metabolism impacts the pathogenesis of autoimmune diseases, with specific emphasis on Th17 and Tfh cells.

• Journal of Medicine and Life Science
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• 제18권2호
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• pp.35-39
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• 2021

Exaggerated acute and late toxicities following radiotherapy have been reported in patients with pre-existing connective tissue diseases, such as systemic lupus and scleroderma. Behcet's disease (BD) is a relapsing multisystem connective tissue disease characterized by vasculitis in the mucocutaneous, ocular, gastrointestinal, respiratory, neurologic, urogenital, articular, and cardiovascular systems. Data concerning the relationship between radiotherapy toxicity and BD are limited in the literature. Here, we report a case of lung cancer treated with radiotherapy (60 Gy) in a patient with BD. No severe radiation-induced toxicity was observed. Radiation-induced toxicity in patients with BD has also been discussed.

• IMMUNE NETWORK
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• 제22권5호
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• pp.37.1-37.16
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• 2022

Autoimmune diseases are caused by a dysfunction of the acquired immune system. In a subset of autoimmune diseases, B cells escaping immune tolerance present autoantigen and produce cytokines and/or autoantibodies, resulting in systemic or organ-specific autoimmunity. Therefore, B cell depletion with monoclonal Abs targeting B cell lineage markers is standard care therapy for several B cell-mediated autoimmune disorders. In the last 5 years, genetically-engineered cellular immunotherapies targeting B cells have shown superior efficacy and long-term remission of B cell malignancies compared to historical clinical outcomes using B cell depletion with monoclonal Ab therapies. This has raised interest in understanding whether similar durable remission could be achieved with use of genetically-engineered cell therapies for autoimmunity. This review will focus on current human clinical trials using engineered cell therapies for B cell-associated autoimmune diseases.

• Toxicological Research
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• 제33권1호
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• pp.63-69
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• 2017

Transmembrane protein 39A (TMEM39A) belongs to the TMEM39 family. TMEM39A gene is a susceptibility locus for multiple sclerosis. In addition, TMEM39A seems to be implicated in systemic lupus erythematosus. However, any possible involvement of TMEM39A in cancer remains largely unknown. In the present report, we provide evidence that TMEM39A may play a role in brain tumors. Western blotting using an anti-TMEM39A antibody indicated that TMEM39A was overexpressed in glioblastoma cell lines, including U87-MG and U251-MG. Deep-sequencing transcriptomic profiling of U87-MG and U251-MG cells revealed that TMEM39A transcripts were upregulated in such cells compared with those of the cerebral cortex. Confocal microscopic analysis of U251-MG cells stained with anti-TMEM39A antibody showed that TMEM39A was located in dot-like structures lying close to the nucleus. TMEM39A probably located to mitochondria or to endosomes. Immunohistochemical analysis of glioma tissue specimens indicated that TMEM39A was markedly upregulated in such samples. Bioinformatic analysis of the Rembrandt knowledge base also supported upregulation of TMEM39A mRNA levels in glioma patients. Together, the results afford strong evidence that TMEM39A is upregulated in glioma cell lines and glioma tissue specimens. Therefore, TMEM39A may serve as a novel diagnostic marker of, and a therapeutic target for, gliomas and other cancers.

• IMMUNE NETWORK
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• 제3권3호
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• pp.227-234
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• 2003

Background: Immunoglobulin (Ig) light chain repertoire has been implicated as a critical determinant in regulation of autoreactive B cells and production of pathogenic anti-DNA antibodies in systemic lupus erythematosus (SLE). We analyzed the impact of Ig ${\lambda}$ chain repertoire on development of autoimmunity in patients with SLE. Methods: We obtained genomic DNA from individual peripheral CD19+ B cells of 3 untreated active SLE patients, and amplified $V{\lambda}$ rearrangements from each single cell by polymerase chain reaction. Results: A total number of 208 $V{\lambda}J{\lambda}$ rearrangements were analyzed. Analyzed sequences included 158 productive rearrangements and 50 nonproductive rearrangements. The differences in $V{\lambda}$ gene usage in the productive and nonproductive repertoire of SLE patients were found compared to the non-autoimmune individuals. $V{\lambda}$ gene, 9A was significantly overrepresented in nonproducative repertoire of SLE patients (P=0.016). In the productive repertoire, $V{\lambda}$ genes, 3L and 1E were found more often in the SLE patients (P=0.001, P=0.043). When the productive and the nonproductive repertoires were compared, 9A was found significantly less in the productive repertoire in the SLE patients (P=0.000). There were no significant differences in the $J{\lambda}$ gene usage between SLE patients and non-autoimmune individuals, but $J{\lambda}2/3$ gene was the most frequently used in SLE, whereas $J{\lambda}7$ gene was the most frequently used in the normal subjects. In the productive SLE $V{\lambda}$ repertoire, 9.4% of the total sequences employed identical CDR3. It was particularly striking to find 7 identical versions of the 1G-$J{\lambda}2/3$ $V{\lambda}J{\lambda}$ rearrangements from one patient and 3 of the same sequence from another patient. Notably, identical $V{\lambda}$ junctions in the SLE patients utilized significantly more homologous joining compared to $V{\lambda}$ junctions of the normal adults (P=0.044). Conclusion: These data demonstrate regulation of ${\lambda}$ light chain expression in the SLE patients by selection of unique $V{\lambda}$ genes. Also, biased selection and clonal expansion of particular $V{\lambda}$ rearrangements are apparent in the SLE ${\lambda}$ repertoire.

• IMMUNE NETWORK
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• 제2권4호
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• pp.227-232
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• 2002

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by diverse clinical manifestations and autoantibody production, which is known to be strongly influenced by genetic factors. Previous studies have revealed the associations of SLE with HLA class II alleles and antiphospholipid antibody system (anticardiolipin antibody (aCL) and anti-${\beta}_2$ glycoprotein I antibody (anti-${\beta}_2$ GPI)). Therefore, we studied the associations of HLA class II alleles with SLE and antiphospholipid antibody system. Methods: The genotyping for HLA-DRB1 and DQB1 alleles were performed in 61 SLE patients and 100 controls by the polymerase chain reaction (PCR)-sequence specific oligonucleotide probe method. ELISA tests for aCL and anti-${\beta}_2$ GPI were performed in 39 of the 61 SLE patients. The results were evaluated statistically by Chi-square test. Results: The frequencies of the HLA-$DRB1^*15$ and $DQB1^*06$ in SLE patients were significantly higher than those in controls. HLA-$DRB1^*12$ was significantly lower in SLE patients than controls. Nine of 39 patients were positive for aCL (IgG) and three were positive for aCL (IgM). One of 39 patients were positive for anti-${\beta}_2$ GPI (IgG) and none of them positive for anti-${\beta}_2$ GPI (IgM). Association of aCL with HLA class II alleles was not observed in our study. Conclusion: According to our results, it was found that HLA-$DRB1^*15$ and $DQB1^*06$ were associated with genetic susceptiblility and $DRB1^*12$ was associated with resistance to SLE in Korean population. No Association of aCL with HLA class II alleles was observed and the positive rate for anti-${\beta}_2$ GPI was very low.

• 대한핵의학회지
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• 제19권1호
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• pp.127-136
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• 1985

To evaluate change of serum $beta_2-microglobulin$ concentration$(s\beta_2-MG)$ and the usefulness of $s\beta_2-MG$ and $s\beta_2-MG/serum$ creatinine concentration(sCr) ratio in various renal diseases, $s\beta_2-MG$ and sCr were measured in 25 normal controls and 90 patients of various renal diseases(16 cases of glomerulonephritis, 12 cases of acute renal failure, 8 cases of chronic renal failure, 24 cases of nephrotic syndrome, 15 cases of tubulointerstitial diseases and 15 cases of lupus nephritis) using $Phadebas^\circledR$ $Beta_2-Micro$ Test kits. The results were as follows; 1) In normal control, the mean value of $s\beta_2-MG$ was $1.65{\pm}0.41mg/l$ and the mean value of $s\beta_2-MG/sCr$ ratio was $0.14{\pm}0.05$. 2) In various renal diseases, the mean value of $s\beta_2-MG$ was $6.74{\pm}5.47mg/l$. The mean value of $s\beta_2-MG/sCr$ ratio was $0.24{\pm}0.11$ and significantly elevated than that of normal control. (p<0.05) 3) The correlation between $s\beta_2-MG$ and sCr in glomerular and tubulointerstitial disease was log $s\beta_2-MG-0.90$ log sCr-0.48 and its correlation coefficient was 0.78(p<0.05). 4) In glomerular disease, the correlation between $s\beta_2-MG$ and sCr was log $s\beta_2-MG-0.89$ log sCr-0.46(r - 0.76) and in tubulointerstitial disease, it was log, $s\beta2-MG-0.95$ log sCr-0.59 (r-0.87). There was no significant difference between the two groups(p<0.05). 5) Among 32 cases of glomerular and tubulointerstitial disease patients, whose sCr was within normal range, 17 cases showed elevated $s\beta_2-MG$. The mean values of $s\beta_2-MG/sCr$ ratio in these patients was $0.30{\pm}0.14$ and significantly elevated than that of normal control(p<0.05). 6) In 15 cases of lupus nephritis, 12 cases showed elevated $s\beta_2-MG$ with normal sCr and 12 cases showed elevated $s\beta_2-MG/sCr$ ratio. With above results, it was found that the $s\beta_2MG$ can be used as an index of glomerular filtration rate as in the case of sCr and that $s\beta_2-MG/sCr$ ratio can be used as a tool in early detection of slightly decreased glomerular filtration rate and in detection of the renal disease of increased $\beta_2-MG$ production.

• 한국식품영양과학회지
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• 제31권5호
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• pp.917-923
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• 2002

청각에서 분리된 항응고 다당류의 혈액응고 저해기작을 검토하였다. 항응고성 다당 획분(CF-30 IV-ii, CF-30-IV)은 내인성 경로와 공통 경로에서 농도 의존적으로 작용한다. 항응고획분(CF -30-IV-ii)은 내인성 경로의 factor asaay시 lupus an ticoagulant 항체의 활성 에 영 향을 주지 않았으나 응고과정 중 factor Ⅷ, Ⅸ, \ulcorner, \ulcorner의 활성을 저해하였다. CF-30-IV-4-ii는 농도의 존적으로 fibrine을 생성시키지 않음으로써 thrombin에 직접 작용하지 않는 antithrombin m의존적 항응고 활성 기작을 보였다. 청각의 항응고 활성은factor assay와thrum bin의 저해 양식을 고려해볼 때 antithrombin III의 활성을 증대시켜 혈액응고 인자 중 serine proteinase의 활성을 저해함으로써 항응고 활성을 나타내는 물질로 판명되었다. CF-30-IV획분의 in vivo 활성을 측정한 결과 꼬리정 맥주사에 의해 150 mg/kg의 농도로 마우스에 투여시 thrombin에 대한 100%의 항치사성 효과를 나타내었다 또한 CF-30-IV를 마우스의 꼬리 정맥에 주입하고 혈액을 채취 ex vivo상에서 항응고 활성을 측정한 결과, 생체내에서 100mg1kg의 농도까지도 시료량에 의존하는 항응고 활성을 보였다

• 정신신체의학
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• 제5권1호
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• pp.89-96
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• 1997

SLE 환자들에서 인지기능의 장애가 있는지를 알아보기 위해서 신경정신과적 병력이 없는 내과 외래 SLE 환자 20명과 정상 대조군 20명을 대상으로 전산화 신경인지기능 검사인 Vienna test system을 시행하고 이를 인지기능에 영향을 미칠 수 있는 임상 변인들과의 연관성을 분석하여 다음과 같은 결과를 얻었다. 1) SLE 환자군과 정상 대조군의 신경인지기능 검사의 각 항목 비교 인식력 검사항목에서 SLE 환자군은 정상 대조군에 비해 정확하게 응답한 반응수가 적었으며 '예'와 '아니오' 중 '아니오'를 정확하게 반응한 수도 적었다. 또한 '예'와 '아니오'에 대해 각각 정확한 반응을 하는 평균 반응시간이 길었으며 검사소요 시간도 길었다. 주의력 검사항목에서는 SLE 환자군이 정상 대조군에 비해 정확하게 응답한 반응수가 적었고, 평균 반응시간이 길었다. 그러나, corsi단기 기억력 검사항목에서는 시각적 단기 기억력 범위와 정확하게 맞춘 총 응답수에서 두군 간에 유의한 차이가 없었다. 표준도형 지능검사항목에서 SLE 환자군은 정상 대조군에 비해 정확하게 응답한 반응수가 적었다. 신경행동학적 인지상태 검사중 기억력 항목에서 SLE 환자군은 정상 대조군에 비해 유의하게 낮은 점수를 보였다. 2) 신경인지기능의 각 항목과 환자군의 연령, 교육연한, SLE 질환 활성도(SLE Disease Activity Index), 우울 증상의 정도, 항 ds-DNA항체. 보체 C3/C4, 스테로이드의 용량 등의 임상 변인들과의 상관관계를 비교하였을 때 통계적으로 유의하지 않았다. 이상의 결과에서 질환 활성도가 낮은 SLE환자들은 과거 신경정신과적 증상의 병력이 없고 병의 이환 기간이 비교적 짧음에도 불구하고 인지기능의 장애를 나타내었다. 그리고 이는 기타 장기의 침범으로 인한 비특이적 영향이 아닌 중추신경계의 침범에 의한 것으로 보이며 우울정도나 스테로이드 용량에 영향을 받지 않는 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제63권1호
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• pp.72-77
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• 2007

저자 등은 19세 남자 환자에서 폐색전증을 동반한 원발성 항인지질증후군 증례를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.