• The Korean Journal of Physiology and Pharmacology
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• 제22권1호
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• pp.1-15
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• 2018

Inflammasomes are intracellular multiprotein complexes that coordinate anti-pathogenic host defense during inflammatory responses in myeloid cells, especially macrophages. Inflammasome activation leads to activation of caspase-1, resulting in the induction of pyroptosis and the secretion of pro-inflammatory cytokines including interleukin $(IL)-1{\beta}$ and IL-18. Although the inflammatory response is an innate host defense mechanism, chronic inflammation is the main cause of rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SS). Since rheumatic diseases are inflammatory/autoimmune disorders, it is reasonable to hypothesize that inflammasomes activated during the inflammatory response play a pivotal role in development and progression of these diseases. Indeed, previous studies have provided important observations that inflammasomes are actively involved in the pathogenesis of inflammatory/autoimmune rheumatic diseases. In this review, we summarize the current knowledge on several types of inflammasomes during macrophage-mediated inflammatory responses and discuss recent research regarding the role of inflammasomes in the pathogenesis of inflammatory/autoimmune rheumatic diseases. This avenue of research could provide new insights for the development of promising therapeutics to treat inflammatory/autoimmune rheumatic diseases.

• 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.

• Childhood Kidney Diseases
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• 제3권1호
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• pp.80-87
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• 1999

목 적 : 루프스 신염은 전신성 홍반성 낭창(systemiclupuserythematosus,SLE)의 가장 심각한 합병증 가운데 하나이지만, 소아 연령에서 루프스 신염에 대한 국내 연구는 미약한 실정이다. 본 연구는 루프스 신염 환자를 대상으로 빈도, 임상상, 치료반응, 예후 등에 대한 기초 조사를 실시하여 향후 전국 규모의 다기관 연구를 위한 기반 자료로 사용하기 위함이다. 방 법 : 1986년부터 1997년 11년 동안 서울대학교 어린이병원 소아과에 입원한 SLE환아 53례 중 신생검상 루프스 신염이 확인된 46례를 대상으로 후향적 의무기록 고찰을 시행하였다. 결 과 : 1) 전체 남녀비는 1:2.5, 루프스 신염의 진단 당시 정중연령은 12.8세(2세-15세 8개월)이었다. 2) ARA 분류 기준 중 형광항핵항체($85.7\%$), 항ds-DNA항체($78.0\%$), 나비모양 홍반($60.8\%$) 등이 가장 빈번히 관찰되었으며, 기타 검사 소견중에서는 C3의 감소($88.9\%$)가 흔하였다. 3) 혈뇨($87.0\%$)는 가장 흔한 신장 증상이었고, 신생검상 41례에서 WHO class IV 병변이 확인되었다. 4) Prednisolone, azathioprine, 경구 또는 정맥 cyclophosphamide 등을 단독 또는 병합치료 결과 대부분 환자에서 질환 활성도가 정상 혹은 중증도 이하로 조절되었으며, 치료 종류에 따른 반응도의 차이는 관찰할 수 없었다. 5) 감염은 치료 경과중 가장 흔한 합병증이었으며, 특히 Varicella-Zoster virus와 candida 감염증이 흔하였다. 결 론 : SLE 환아중 루프스 신염의 빈도는 $87.0\%$이었고, 그중 $89.1\%$가 장기적 예후가 불량한 WHO class IV 로 확인되었다. 따라서 신염 초기의 적극적인 면역억제제 사용이 장기적 예후 향상에 도움을 주리라 사료되며, 이에 대한 장기간의 전향적-비교연구를 위하여 다기관 공동연구가 절실히 필요하다.

• Clinical and Experimental Pediatrics
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• 제51권11호
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• pp.1217-1221
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• 2008

목 적: SLE에서는 진단 당시 및 경과 중에 약 15-20%에서 혈소판 감소가 발생하며, 5-16%에서는 혈소판 감소증이 첫 임상증상으로 발생할 수 있으므로 소아 ITP와 SLE와의 연관성이 강력히 제기되고 있다. 한편 항핵항체는 여러 자가면역질환의 선별검사로 주로 이용되고 있는데, 특히 자가면역질환의 임상증상이 발현되기 수개월 혹은 수년 전에 발현될 수 있다. 따라서 저자들은 소아 ITP로 진단된 환자들에서 항핵항체 검사의 양성률 및 임상적 의의를 조사하고자 본 연구를 시작하였다. 방 법: 2003년 1월부터 2006년 12월까지 부산대학교병원 소아청소년과에서 급성 ITP로 진단 받고, 진단 당시에 항핵항체 검사를 시행하였던 77예의 환아를 대상으로 하였다. 항핵항체 검사는 정량 및 정성 검사를 시행하였고, 1:40 이상을 양성으로 판정하였다. 항핵항체 검사 상 양성인 환자들은 1년 이상 역가를 주기적으로 추적관찰 하였다. 결 과: 1) 진단 당시 항핵항체 검사를 시행한 77예의 ITP 환자 중 남아는 38예(49.4%), 여아는 39예(50.5%)였으며, 평균 연령은 4.5세였고, 16예(20.8%)에서 항핵항체 검사 상 양성을 보였다. 2) 항핵항체 양성인 군에서 항핵항체의 정량 역가의 분포는 1:80-1:1,280으로 1:640이 16명 중 5명(30.7%)으로 가장 많았고, 항핵항체의 형은 homogeneous 형이 16명 중 6명(37.5%)으로 가장 많았다. 3) 항핵항체가 양성인 군의 평균 연령은 9.3세로 음성인 군의 3.3세에 비해 진단 당시 평균 연령이 의미 있게 높았다(P<0.05). 4) 항핵항체가 음성인 군의 남녀비는 비슷하였던 반면 항핵항체가 양성인 군은 여아가 81.3%로 현저히 높았다(P<0.05). 5) 진단 당시 혈소판 정중값은 항핵항체 양성군에서는 $18,400/{\mu}L$, 음성군에서는 $21,800/{\mu}L$으로 두 군 사이에 의미 있는 차이가 없었다. 6) 진단 당시 항핵항체의 역가 및 형은 만성 ITP 및 SLE로의 진행과 의의있는 관련이 없었다. 7) 급성 ITP 진단 당시 항핵항체 양성이었던 환자 중 1명이 추적관찰 41개월 후 SLE로 최종 진단되었다. 결 론: 소아 급성 ITP 환자에서 ANA 양성인 경우가 비교적 흔한 것으로 나타났으며, 만성 ITP와 SLE로의 진행에 대한 연관성은 더 많은 환자를 대상으로 한 연구를 통하여 밝혀져야 할 것이다.

• 대한두경부종양학회지
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• 제16권2호
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• pp.212-215
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• 2000

Background and Objective: Kikuchi's disease(KD) is an idiopathic, self-limited lymphadenopathy that was described as a distinctive type of necrotizing lymphadenitis affecting primarily cervical lymph nodes of young adults independently by Kikuchi and Fujimoto et al at first in 1972. The purpose of this study is a knowledge about clinicopathologic findings, many laboratory tests and differentiation of KD from other lymphadenitis due to lymphoma, systemic lupus erythematosus(SLE) and many viral disease. Materials and Methods: Thirty-four case of KD collected at Chonnam University Hospital in Kwang-Ju from 1992 through 2000 were evaluated with retrospective chart review. Results: The patients were consisted of 11 men and 23 women. All patients had tender or nontender cervical mass and fever was the most common associated symptom. The others was pain, weight loss, chills, cold sweating and headache et al. Multiple bilateral involvement of cervical lymphnodes was 25 cases(74%) and solitary involvement was 9 cases(26%). In laboratory tests, leukopenia was 12 cases(75%), elevated ESR 5 cases (34%) and elevated LDH 11 cases(69%). Conclusion: KD is necessary to differentiate from lymphoma and SLE, because of the different of therapeutic modality and prognosis. The diagnosis is established on the basis of histopathologic studies with excisional biopsy of lymph node.

• IMMUNE NETWORK
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• 제4권3호
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• pp.161-165
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• 2004

Background: Anti-cardiolipin antibody (Anti-CL Ab) is one of the various antiphospholipid antibodies (Anti-PL Abs) and found in the plasma of patients with systemic lupus erythematosus (SLE), atherosclerosis, and other infectious diseases. While anti-PL Abs found in the sera of patients with infectious diseases bind directly to CL, binding of anti-PL Abs to CL circulating in the sera of patients with autoimmune diseases is mediated by $\beta_2-$glycoprotein 1 ($\beta_2-GP1$). The purpose of this study is to investigate the effect of <$\beta_2-GP1$ on the antigen binding assay of anti-CL Abs present in the sera of patients with atherosclerosis, which has been known as one of autoimmune diseases. Methods: ELISA was performed with sera containing anti-CL Abs from three patients with atherosclerosis in the presence or absence of $\beta_2-GP1$ or FBS. Results: Reactivity of anti-CL Abs to CL was increased in the presence of $\beta_2-GP1$ or FBS in a dose dependent manner. Conclusion: <$\beta_2-GP1$ or FBS could be used as co-factor in CL ELISA with anti-CL Abs present in the sera of patients with atherosclerosis. It is suggested that anti-CL Abs found in atherosclerosis patients are similar in terms of antigen binding property to those circulating in the patients with autoimmune diseases, not to infectious diseases.

• 동의생리병리학회지
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• 제21권6호
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• pp.1663-1669
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• 2007

Acute transverse myelitis(ATM) is defined as an acute intramedullary dysfunction of the spinal cord, ascendng or static involving both halves of the cord and appearing without any history of previous neurological diseases due to traumatic accident, tumor of all kind, encephalitis and of course excluding all possible viral, bacterial and fungal infection. It is mainly characterized by acute motor disorder of both limbs in respect to which spinal segments are affected as well as sensory disorder and dysuria & dyschezia. The exact cause is unknown, however it is recently suggested that immunological factors are highly involved. It has been reported by several reliable sources that it is often accompanied by immunological diseases such as systemic lupus erythematosus(SLE). As treatments non steroid anti-inflammatory drugs(NSAIDS) are primarily recommended as to steroids, limited doses are injected only with the proper prescription from the physician. Operative methods are not options as traumatic accidents and tumors are excluded as factors. To enhance muscle strength and prevent articular contracture physical therapy and passive exercise is imperative. The following patient whose chief complaints were mainly about hypoesthesia of Rt. lower limb and stiffness of phalanges of both fingers as well as to weakness of lower extermity. Therefore it has been diagnosed as arthalgia syndrome. In oriental medicine factors such as wind evil heat-evil, dampness-heat evil, cold evil cause the arthalgia syndrome. In this case the patient was diagnosed as dampness-heat evil and herbal medicine Chunglijagam-Tang and Dong-Qi acupuncture was applied to treat bladder disorder.

• Annals of Clinical Neurophysiology
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• 제9권1호
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• pp.11-15
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• 2007

Background: The term "overlap syndromes" designates a group of diseases in which polymyositis (PM) or dermatomyositis (DM) is associated with some other disorders of connective tissues. The aim of this study was to delineate the clinical features, laboratory findings, and outcome of treatment of "overlap syndromes" Methods: We analyzed the medical records of 16 patients (PM in 10, DM in 6) with well documented "overlap syndromes" between 1997 and 2004. The diagnosis was made when the criteria for two different disorders were fulfilled. Results: All patients were female. Age of onset ranged from 14 to 52 years (mean 29.8 years) with peak incidence in the third and fourth decades. Systemic lupus erythematosus (SLE) was associated in 10, systemic sclerosis in 7, and rheumatoid arthritis in 3 patients. Four of the patients had two different connective tissue diseases simultaneously. The characteristic clinical features were muscle weakness, arthralgia, Raynaud's phenomenon, and myalgia. In laboratory tests, creatine kinase (CK), lactic dehydrogenase (LDH), and transaminases were usually abnormal. Positive antinuclear antibody (ANA), rheumatoid factor (RF), and cryoglobulin were found in 100%, 69%, and 67% of the patients, respectively. Needle electromyography (EMG) showed abnormal findings compatible with myopathy in 15 patients. The pathology of muscle biopsy from 14 patients revealed findings compatible with inflammatory myopathy. Glucocorticoids were administered to 15 patients. The muscle strength improved in all the treated patients, which was well correlated with repeat CK level and EMG findings. Conclusions: The presence of autoantibodies such as ANA, RF, and cryoglobulin in patients with PM or DM highly suggests the possibility of an overlap syndromes. These syndromes reveal a strong female predominance. The myositis associated with them usually shows a good response to glucocorticoids treatment.

• IMMUNE NETWORK
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• 제14권1호
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• pp.21-29
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• 2014

Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

• Asian-Australasian Journal of Animal Sciences
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• 제31권1호
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• pp.138-148
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• 2018

Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0.8 mg ZEN/kg feed. Kidney samples were collected after treatment, and RNA-seq was used to investigate the effects on immune-related genes and gene networks. Results: A total of 186 differentially expressed genes (DEGs) were screened (120 upregulated and 66 downregulated). Gene ontology analysis revealed that the immune response, and cellular and metabolic processes were significantly controlled by these DEGs. The inflammatory stimulation might be an effect of the following enriched Kyoto encyclopedia of genes and genomes pathway analysis found related to immune and disease responses: cytokine-cytokine receptor interaction, chemokine signaling pathway, toll-like receptor signaling pathway, systemic lupus erythematosus (SLE), tuberculosis, Epstein-Barr virus infection, and chemical carcinogenesis. The effects of DON and ZEN on genome-wide expression were assessed, and it was found that the DEGs associated with inflammatory cytokines (interleukin 10 receptor, beta, chemokine [C-X-C motif] ligand 9, CXCL10, chemokine [C-C motif] ligand 4), proliferation (insulin like growth factor binding protein 4, IgG heavy chain, receptor-type tyrosine-protein phosphatase C, cytochrome P450 1A1, ATP-binding cassette sub-family 8), and other immune response networks (lysozyme, complement component 4 binding protein alpha, oligoadenylate synthetase 2, signaling lymphocytic activation molecule-9, ${\alpha}$-aminoadipic semialdehyde dehydrogenase, Ig lambda chain c region, pyruvate dehydrogenase kinase, isozyme 4, carboxylesterase 1), were suppressed by DON and ZEN. Conclusion: In summary, our results indicate that high concentrations of DON and ZEN suppress the inflammatory response in kidneys, leading to potential effects on immune homeostasis.