Systemic lupus erythematous (SLE) is a systemic autoimmune disease with multi-organ inflammation caused by the production of pathogenic autoantibodies and immune complexes reflecting a global loss of tolerance. Lupus nephritis (LN) is present in approximately 60% of SLE patients and is considered a major predictor of a poor prognosis. To date, many studies utilizing genomics, transcriptomics, epigenetics, metabolomics, and microbiome have been conducted on a range of animal models and lupus patients to understand the pathogenesis of SLE and LN. Collectively, these studies support the concept that LN is caused by increased cell death, which has not been properly dealt with; abnormal innate immunity; hyperactive adaptive immunity; and genetic variants triggered by a range of environmental factors. This review summarizes the results from studies that contributed strongly to elucidating the pathogenesis of SLE and LN, highlighting the immunological and non-immunological mechanisms.
Adaptive Immunity ; Allergy and Immunology ; Antigen-Antibody Complex ; Apoptosis ; Autoantibodies ; Autoimmune Diseases ; Cell Death ; Epigenomics ; Genomics ; Humans ; Immunity, Innate ; Inflammation ; Lupus Nephritis* ; Lymphocytes ; Metabolomics ; Microbiota ; Models, Animal ; Prognosis ; Wolves*

The prevalence of systemic lupus erythematosus (SLE) varies significantly based on ethnicity rather than geographic distribution; thus, the prevalence is higher in Asian, Hispanic, and Black African populations than in European populations. The risk of developing lupus nephritis (LN) is the highest among Asian populations. Therefore, we hypothesize that human genetic diversity between races has occurred through the early human migration and human genetic adaptation to various environments, with a particular focus on pathogens. Additionally, we compile the currently available evidence on the ethnic gene diversity of SLE and how it relates to disease severity. The human leukocyte antigen (HLA) locus is well established as associated with susceptibility to SLE; specific allele distributions have been observed across diverse populations. Notably, specific amino acid residues within these HLA loci demonstrate significant associations with SLE risk. The non-HLA genetic loci associated with SLE risk also varies across diverse ancestries, implicating distinct immunological pathways, such as the type-I interferon and janus kinase–signal transducers and activators of transcription (JAK–STAT) pathways in Asians, the type-II interferon signaling pathway in Europeans, and B cell activation pathway in Africans. Furthermore, assessing individual genetic susceptibility using genetic risk scores (GRS) for SLE helps to reveal the diverse prevalence, age of onset, and clinical phenotypes across different ethnicities. A higher GRS increases the risk of LN and the severity of SLE. Therefore, understanding ethnic gene diversity is crucial for elucidating disease mechanisms and SLE severity, which could enable the development of novel drugs specific to each race.

Hemorrhagic cystitis is potentially life-threatening sequellae of chemotherapy using oxazaphosphorine alkylating agents (cyclophosphamide and ifosfamide). Mesna contains a sulfhydryl group that is believed to bind acrolein within the urinary collecting system and reduce the hemorrhagic cystitis without affecting the chemotherapeutic potential. To date, about thirty cases of hypersensitivity or allergic reactions of the delayed and urticarial type associated with mesna have been reported. We reported two patients with systemic lupus erythematosus who developed facial rash and flushing associated with mesna which imitate malar rash.
Acrolein ; Alkylating Agents ; Cyclophosphamide ; Cystitis ; Drug Therapy ; Exanthema* ; Flushing ; Humans ; Hypersensitivity* ; Lupus Erythematosus, Systemic ; Mesna*

PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is characterized by a chronic T-cell response that has escaped normal control mechanisms. This review summarizes recent insights in pathways that are functional in RA and that favor continuous and pathogenic T-cell activation. RECENT FINDINGS: T-cell activation is ultimately determined by positive signals from costimulatory molecules and negative signals from regulatory T cells. Blockade of the classic costimulatory pathway, CD28-CD80 or CD86, is beneficial in RA. Additional pathways that predominantly control the activation of memory and effector T cells are functionally important in synovial inflammation. Some of these costimulatory molecules(such as stimulatory killer cell immunoglobulin-like receptors and NKG2D) appear to be relatively specific for RA and not to play a role in normal immune responses. In addition to this predominance of positive signals, age-disproportionate decline in thymic activity in RA may lead to a diminution of regulatory T cells and loss of their negative signals. SUMMARY: The successful treatment trial of RA with CTLA-4Ig clearly documents the importance of T-cell costimulation in RA disease activity. Novel costimulatory pathways may be of even greater significance than CD28 in RA and may represent promising new therapeutic targets. The finding of reduced thymic activity in RA is exciting and will stimulate further studies of T-cell homeostasis and the function of regulatory cells.
Arthritis, Rheumatoid* ; Autoimmunity ; Homeostasis ; Inflammation ; Lymphocytes* ; Memory ; Receptors, KIR ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; United Nations

BACKGROUND: Several kinds of stents have shown their safety and efficacy to treat acute or subacute closure after balloon angioplasty as well as to reduce restenosis rate. However, one of the limitations of stents is difficult to deploy especially in tortuos vessels, lesions at a bend, and distal to previously deployed stents. The Micro stent II, which was one of the most recently developed stents, ia a rapid-exchage balloon expandable stainless steel stent with a zigzag design connected with a continuous single weld in each 3mm segments. It scores over excellent trackability and optimum radio-opacity. Therefore, it is easy to operate and feasible in tortuous, distal lesions and variety of lesion lengths. We report our experiences with Micro-II stent implanatation in the first 76 patients at Tonsei cardiovascular center to assess its safety and efficacy in patients with complex coronary anatomy and clinical results in the first months. METHODS: Between January 1996 and July 1996, eighty-six Micro-II stent were implanted in the coronary arteries of 76 patients(male 65.8%, age 59+/-10 year). Forty-five patients had unstable angina, the others had stable angina(17pts), acute myocardial infarction(14pts). RESULTS: 1) Indication of stenting was de novo 51(59.3%), suboptimal result 25(29.1%), restenosis 1(1.2%) and 9(10.4%) of lesions were stented in bail out situation. 2) Single stent were implanted in 76(88.4%)lesions, overlapping stent in 10(11.6%)lesions. Among overlapping stents, the second stent with Micro-II stent and with another kind of stent were 4.6%, 7.0%, respectively. 3) Procedure related complication including a subacute closure was occurred in 1(1.2%) patient who had distal dissection and 45% residual stenosis. In 12(14%) lesions, preistent dissection has been noticed after stent impantation. 4) Angiographic success(defined as a residual stenosis of <30% without major dissection) was achieved in 82 of 86 attempts(95.3%). The procedual success rate(defined as a residual stenosis of <30% without occurrence of major clinical events within 4 weeks after procesure) was 96.1%(73/76 patients). Angiographic success and procedural success rate in calcified lesion were 100% and 100%, respectively. Angiographic success and procedural success rate in more than 45` angulated lesion were 97% and 100%, respectively. 5) The mean minimal luminal diameter of the target lesions was increased from 0.42+/-0.40mm before stent implantation to 2.93+/-0.50mm(p<0.001). The percentage of diameter stenosis was reduced from 86.49+/-13.04% to 1.40+/-7.11%(p<0.001) after stent implantation. CONCLUSION: Coronary stenting with AVE Micro-II stent can be safety performed and is particularly beneficial in tortuous and calcified arteries. There was a high tendency for peristent dissection which need to special consideration to avoid. Follow-up data is needed to assess mid and term patency. Coronary artery disease . AVE Micro-II stent . Immediate results.
Angina, Unstable ; Angioplasty, Balloon ; Arteries ; Constriction, Pathologic ; Coronary Artery Disease ; Coronary Vessels ; Follow-Up Studies ; Humans ; Phenobarbital ; Stainless Steel ; Stents*

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL­23/IL­17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL­23/IL­17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

Radiographic axial spondyloarthritis (r-axSpA), a chronic inflammatory disease, can cause significant radiographic damage to the axial skeleton. Regarding the pathogenic mechanism, association of r-axSpA with tumor necrosis factor (TNF) and the interleukin-23/17 (IL­23/IL­17) pathway has been reported. Development of extraarticular manifestations, including uveitis, inflammatory bowel disease, and psoriasis, has been reported in some patients. The pivotal role of human leukocyte antigenB27 in the pathogenesis of r-axSpA remains to be clarified. Symptoms usually start in late adolescence or early adulthood, and disease progression can vary in each patient, with clinical manifestations ranging from mild joint stiffness without radiographic changes to advanced manifestations including complete fusion of the spine, and severe arthritis of the hip, and could include peripheral arthritis and extraarticular manifestations. The modified New York criteria was used previously in diagnosis of r-axSpA. However, early diagnosis of the disease prior to development of bone deformity was required due to development of biological agents. As a result of Assessment of SpondyloArthritis international Society (ASAS), the classification was improved in part for diagnosis of spondyloarthritis prior to development of bone deformity. The diagnosis is based on comprehensive laboratory findings, physical examinations, and radiologic findings. Medical treatment for r-axSpA involves the use of a stepwise strategy, starting with administration of nonsteroidal anti-inflammatory drugs and physiotherapy, and progressing to sulfasalazine or methotrexate and biologics including TNF-α inhibitors or IL-17 inhibitors as needed. Use of Janus kinase inhibitors has been recently reported.

BACKGROUND: Diffuse panbronchiolitis(DPB) is a chronic inflammatory disease affecting the respiratory bronchioles which was first described in Japan in 1966. DPB is prevalent in Japan and is known to be very rare in western countries. The first cases of DPB were reported in Korea in 1992 and the number of the patients has been increasing. The prognosis of DPR had been very poor because there had been no effective treatment for the disease. Hut it has been dramatically changed since the introduction of low-dose long-term erythromycin therapy. In Korea, there is rare experience of 1ong-term follow-up of DPH patients and we presents the results of mean 21.6 months of follow-up after erythromycin treatment. METHODS: We analyzed the long-term follow-up data of 25 DPH patients who were diagnosed in Seoul National University Hospital during the period from September 1989 to December 1994 and followed up more than 6 months with erythromycin therapy. We tried erythromycin 250mg b.i.d. on all the patients and analyzed the changes of subjective symptoms, physical signs, pulmonary function tests, and chest X-rays. RESULTS: 1) The mean follow-up period was 21.6 months. 2) Subjective symptoms improved in 96% of the patients within 3 months and 76% of the patients showed no symptom after 18 months of treatment. 3) Crackles and wheezing decreased in all patients within 3 months and completely disappeared in 76% of the patients after 18 months of treatment. 4) Diffuse small nodular lesions on chest X-ray decreased in 56% of the patients within 3 months and chest PA was normal in 32% of the patients after 12months of treatment. 5) FVC and FEV1 increased remarkably during the first 3 months and slowly increased thereafter, reaching normal level after 12 months of treatment. FEV1/FVC was 60.4% before treatment and in- creased slowly reaching 76.1% after 24 months of treatment. 6) Erythromycin therapy could be finished in 7 patients. The mean duration of medication was 26 months and no evidence of recurrence was found in 6 months of follow-up. 7) No patients had experienced the side effect of erythromycin, CONCLUSION: The prognosis of DPR is very goad when treated with erythromycin. And at least 2 years of erythromycin treatment seems to be needed for DPB patients.
Bronchioles ; Erythromycin* ; Follow-Up Studies* ; Humans ; Japan ; Korea ; Prognosis ; Recurrence ; Respiratory Function Tests ; Respiratory Sounds ; Seoul ; Thorax

BACKGROUNDS: Rheumatoid factor (RF) is common serological marker for the diagnosis of rheumatoid arthritis (RA), but its sensitivity and specificity are not satisfactory for the diagnosis of RA. Therefore, we investigated the diagnostic performance of a new antifilaggrin antibody test by enzyme linked immunosorbent assay (ELISA) in RA. METHODS: Recombinant human filaggrin was deiminated in vitro by peptidylarginine deiminase and used as the coating antigen for ELISA. We performed the RF and the antifilaggrin antibody for 324 RA patients, 251 non-RA patients (rheumatic diseases other than RA), and 286 normal individuals and evaluated the sensitivities and specificities of RF and antifilaggrin antibody. Optimal cut off values were calculated as mean+2SD in 95% confidence interval except 3SD for 286 normal individuals. Optimal cut off values of antifilaggrin antibody and RF were 9.6 U/ml and 12 U/ml, respectively. RESULTS: The sensitivities and specificities of antifilaggrin antibody were 44.8% and 89.2% at optimal cut off values. The sensitivity and specificity of RF were 75.0% and 83.3%. Combination of "antifilaggrin antibody and RF" showed significantly high specificity of 95.2% and that of "antifilaggrin antibody or RF" showed slightly high sensitivity of 79.3% at optimal cut off values. Antifilaggrin antibody was positive in 17.3% among 81 sero-negative RA patients. CONCLUSION: We considered that antifilaggrin antibody could be used a supplementary test of RF for the diagnosis of RA, because "antifilaggrin antibody and RF" had higher diagnostic specificity than RF alone and antifilaggrin antibody test was easy, convenient ELISA method in performance.
Arthritis, Rheumatoid* ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Humans ; Rheumatoid Factor ; Sensitivity and Specificity