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1.
Immunol Med ; : 1-12, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38627989

ABSTRACT

Vaccines against coronavirus disease 2019 (COVID-19) have been distributed in most countries for the prevention of onset and aggravation of COVID-19. Recently, there have been increasing numbers of reports on new-onset autoimmune and autoinflammatory diseases following COVID-19 vaccination, however, only little information is available on the long-term safety of these vaccines. Here, we experienced three cases of new-onset rheumatic diseases following COVID-19 vaccination, one case each of rheumatoid arthritis (RA), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and systemic lupus erythematosus (SLE). The symptom onset ranged from one day to a few days following vaccination. The patients of AAV and SLE were treated successfully with glucocorticoid therapy, and the patient of RA died due to COVID-19. In the literature review of new-onset rheumatic diseases following COVID-19 vaccination, which including seven cases of RA, 37 cases of AAV and 18 cases of SLE, the mean time from vaccination to onset was approximately 11 to 12 days. Most cases improved with glucocorticoid, immunosuppressive drugs and biologic agents. Although such adverse effects are rare, and vaccines are useful in prevent onset and severity of infections, continued accumulation of similar cases is important in terms of examining the long-term safety and understanding pathogenic mechanism of rheumatic diseases.

2.
Intern Med ; 62(24): 3699-3706, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37839879

ABSTRACT

We present the case of a 42-year-old woman with rheumatoid arthritis and Sjögren's syndrome treated with adalimumab who developed immune-mediated necrotizing myopathy (IMNM) and trigeminal neuropathy after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination. Trigeminal neuralgia and elevated serum creatine kinase levels emerged 12 days post-vaccination, followed by myalgia in the femoral muscles. IMNM was histologically diagnosed. The pathogenesis may involve molecular mimicry between the SARS-CoV-2 spike glycoprotein and autologous tissues triggered by vaccination. This case emphasizes the association between SARS-CoV-2 vaccination, tumor necrosis factor inhibitor, IMNM, and trigeminal neuropathy, as well as the importance of monitoring immune-mediated adverse events following SARS-CoV-2 vaccination in patients with autoimmune disease.


Subject(s)
Arthritis, Rheumatoid , Autoimmune Diseases , COVID-19 , Myositis , Sjogren's Syndrome , Trigeminal Nerve Diseases , Female , Humans , Adult , Sjogren's Syndrome/complications , SARS-CoV-2 , COVID-19 Vaccines/adverse effects , COVID-19/complications , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Myositis/etiology , RNA, Messenger , Vaccination
3.
Intern Med ; 62(11): 1683-1689, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36288993

ABSTRACT

We encountered a 57-year-old Japanese woman with encapsulating peritoneal sclerosis (EPS) in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis. The patient was admitted to our hospital because of ascites retention. Administration of tocilizumab, an anti-interleukin-6 receptor antibody, for her RA reduced the refractory ascites remarkably; however, she developed sudden acute gastrointestinal bleeding and died a year later. On autopsy, sclerotic thickening of the peritoneum showed diffuse infiltration of podoplanin-positive fibroblast-like cells, and a diagnosis of EPS was made. EPS rarely occurs in SLE, and tocilizumab may be a new treatment candidate for EPS.


Subject(s)
Arthritis, Rheumatoid , Lupus Erythematosus, Systemic , Peritoneal Fibrosis , Scleroderma, Systemic , Female , Humans , Middle Aged , Peritoneal Fibrosis/etiology , Ascites/complications , Arthritis, Rheumatoid/complications , Lupus Erythematosus, Systemic/complications , Scleroderma, Systemic/complications
4.
Intern Med ; 62(2): 299-305, 2023 Jan 15.
Article in English | MEDLINE | ID: mdl-36351580

ABSTRACT

Since December 2020, coronavirus disease 2019 (COVID-19) vaccines have been distributed in most countries to prevent the onset and aggravation of COVID-19. There is little information regarding the long-term safety of the vaccines. We report three cases and a literature review of new-onset adult-onset Still's disease (AOSD) that occurred following COVID-19 vaccination. Our cases include moderate to severe AOSD, and two were complicated with macrophage activation syndrome. Seventeen cases of new-onset or relapse of AOSD following COVID-19 vaccination, including 14 identified in the literature review and our 3 patients, were all treated successfully with glucocorticoid therapy, immunosuppressive drugs, or biologic agents.


Subject(s)
COVID-19 Vaccines , COVID-19 , Still's Disease, Adult-Onset , Adult , Humans , COVID-19/complications , COVID-19 Vaccines/adverse effects , Immunosuppressive Agents/adverse effects , Still's Disease, Adult-Onset/etiology , Still's Disease, Adult-Onset/complications , Vaccination/adverse effects
5.
J Scleroderma Relat Disord ; 7(2): NP4-NP8, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35585949

ABSTRACT

Introduction: Most pulmonary vasodilators are administered orally; however, in patients with pulmonary hypertension undergoing gastrointestinal surgery, a switch to parenteral drugs is needed. Parenteral pulmonary vasodilators carry a risk of infection and reduced quality of life owing to long-term central venous catheterization; therefore, it is preferable to switch them to oral vasodilators after surgery. Here, we present the case of a patient with systemic sclerosis complicated by pulmonary hypertension and colon cancer, for which treatment was successfully switched from epoprostenol to selexipag postoperatively. Case Description: A 59-year-old woman, who was diagnosed with mixed group I and III pulmonary hypertension and systemic sclerosis, was on oral triple pulmonary vasodilators for pulmonary hypertension and Raynaud's phenomenon. She was diagnosed as having colon cancer 3 months before admission. Despite the severe pulmonary condition and treatment with oral triple pulmonary vasodilators, colon cancer resection surgery was performed with the management for pulmonary hypertension through multidisciplinary treatments in collaboration with cardiology specialists. Medications for patients with pulmonary hypertension undergoing gastrointestinal surgery need to be switched from oral vasodilators to epoprostenol perioperatively. On postoperative day 19, 0.4 mg/day of selexipag was administered with epoprostenol. Subsequently, the epoprostenol dosage was gradually decreased, and selexipag was increased. On postoperative day 30, the dose of selexipag was increased to 1.2 mg/day and epoprostenol was discontinued. The patient was discharged on postoperative day 40. Conclusion: In our case, transition from epoprostenol to selexipag contributed to a more useful management strategy for systemic sclerosis and pulmonary hypertension in the postoperative period.

6.
Mod Rheumatol ; 30(6): 959-966, 2020 Nov.
Article in English | MEDLINE | ID: mdl-31615315

ABSTRACT

Background: Pentraxin 3 (PTX3) has an important role in inflammation, immunity, and atherosclerosis. Rheumatoid arthritis (RA) is a chronic inflammatory disease featuring both joint damage and atherosclerosis. We investigated whether the plasma PTX3 level was associated with progression of joint destruction and subclinical atherosclerosis in RA patients.Methods: Plasma PTX3 levels were measured in 72 women with RA and 80 female control subjects. In RA patients, we also evaluated clinical characteristics, medications, and at one and three years, joint damage and atherosclerosis. Then we investigated whether PTX3 was associated with progression of joint destruction or an increase of carotid intima-media thickness (IMT).Results: Plasma PTX3 levels were significantly higher in the RA patients than in healthy controls (4.05 ± 2.91 ng/mL vs. 1.61 ± 1.05 ng/mL, p < .001). By multivariate linear regression analysis, the plasma pentraxin 3 level was independently associated with radiographic progression of joint damage for 3 years in the RA patients after adjustment for age, disease duration, body mass index, rheumatoid factor, MMP-3, Disease Activity Score 28-ESR, postmenopausal status, current use of corticosteroids and biologic use. On the other hands, pentraxin 3 was not associated with an increase of carotid intima-media thickness in RA patients.Conclusion: Female RA patients had elevated plasma PTX3 levels compared with control female subjects. PTX3 was independently associated with radiographic progression of joint damage in the RA patients, but not with carotid atherosclerosis.


Subject(s)
Arthritis, Rheumatoid/blood , C-Reactive Protein/analysis , Carotid Artery Diseases/blood , Joints/diagnostic imaging , Serum Amyloid P-Component/analysis , Adult , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/pathology , Biomarkers/blood , Body Mass Index , Carotid Artery Diseases/complications , Carotid Artery Diseases/pathology , Carotid Intima-Media Thickness , Disease Progression , Female , Humans , Joints/pathology , Male , Middle Aged
7.
Mod Rheumatol ; 28(5): 736-757, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29651907

ABSTRACT

OBJECTIVES: Using an expert- and data-driven methodology, we have constructed the first clinical practice guidelines (CPGs) for adult Still's disease (ASD) after complete systematic review (SR) of the literature based upon the Medical Information Network Distribution Service (Minds) procedure. METHODS: The CPG committee for ASD organized by the Research Team for Autoimmune Diseases, the Research Program for Intractable Disease of the Japanese Ministry of Health, Labour, and Welfare has developed CPG for ASD 2017, according to the procedure proposed by Minds. The CPG development process includes (1) clarification of the purpose of CPG, (2) organization of the steering committee, (3) organization of the CPG committee and secretariat, (4) defining the scope (setting of clinical questions (CQs)), (5) SR, (6) development of recommendations, (7) drafting the CPG, (8) external evaluation and public comments, and (9) release. Because we wanted to construct CPG for ASD to encompass both adult-onset Still's disease (AOSD) and adult patients with systemic juvenile idiopathic arthritis (sJIA), we also included SR data from sJIA in this study. RESULTS: Twenty-six CQs were selected and roughly divided into the following items: (1) clinical findings (CQs 1-4), (2) laboratory findings (CQs 5-8), (3) complications (CQs 9-13), (4) treatment with oral medicine (CQs 14-19), (5) treatment with biological reagents (CQs 20-23), and (6) treatments for sJIA (CQs 25-26). Recommendations and the strength of the recommendations for these CQs were decided by a modified Delphi method. CONCLUSION: We have developed the first published CPG for ASD including AOSD and sJIA, which includes 26 CQs and recommendations. This guideline will help rheumatologists, non-specialized physicians, other healthcare providers, medical and health-related students, and patients and their family members to understand and treat ASD.


Subject(s)
Evidence-Based Medicine/methods , Practice Guidelines as Topic , Still's Disease, Adult-Onset/drug therapy , Evidence-Based Medicine/standards , Humans , Still's Disease, Adult-Onset/diagnosis
8.
Mod Rheumatol ; 28(4): 642-648, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29120258

ABSTRACT

OBJECTIVE: To evaluate the performance of the 2012 Systemic Lupus International Collaborating Clinics criteria (SLICC-12) on classifying systemic lupus erythematosus (SLE) in an uncontrolled multi-centered study with real-life scenario of the patients in Japan. METHODS: This study comprised 495 patients with SLE or non-SLE rheumatic diseases and allied conditions from 12 institutes in Japan. Chart review of each patient was performed by the 27 expert rheumatologists and diagnosis of 487 cases reached to the consensus. Value of the SLICC-12 on SLE classification was analyzed comparing with the 1997 revised American College of Rheumatology SLE classification criteria (ACR-97) employing the expert-consented diagnoses. RESULTS: Compared to the ACR-97, the SLICC-12 had a higher sensitivity (ACR-97 vs. SLICC-12: 0.88 vs. 0.99, p < .01) and comparable specificity (0.85 vs. 0.80). The rate of misclassification (0.14 vs. 0.11) or the area under the receiver operating characteristic curves (0.863 vs. 0.894) was not statistically different. In the cases that diagnoses corresponded in high rates among experts, both criteria showed high accordance of SLE classification over 85% with the expert diagnoses. CONCLUSION: Although employment of SLICC-12 for the classification for SLE should be carefully considered, the SLICC-12 showed the higher sensitivity on classifying SLE in Japanese population.


Subject(s)
Lupus Erythematosus, Systemic/pathology , Severity of Illness Index , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Japan , Lupus Erythematosus, Systemic/classification , Male , Middle Aged
9.
Article in Japanese | MEDLINE | ID: mdl-25765688

ABSTRACT

Rheumatoid arthritis (RA) affects mainly women during their childbearing years. As aging of childbirth advances in Japan, women who plan pregnancy would increase after they developed RA. Recent findings showed that high disease activity of RA might impair fertility. Planning pregnancy is preferable after female patients achive and maintain low disease activity or remission of RA. Women on methotrexate, which is the anchor drug for RA, need to discontinue the medication with a high risk of causing birth defects during conception and pregnancy. Data of RA patients exposed TNF inhibitors during pregnancy has been accumulating in recent years. These data suggest that increased risk of spontaneous abortion and congenital abnomalies has not been observed. Although there is insufficient data about safety of breastfeeding while using TNF inhibitors, the secretion of the drugs in breast milk is very little and fetal toxicity has not been observed. Since long term safety of children exposed TNF inhibitors in uterus has not been established, we should discontinue the drugs as soon as pregnancy is recognized. TNF inhibitors may be an useful tools for management of active RA resistant to conventional DMARDs in women who desire to bear children.


Subject(s)
Antirheumatic Agents/administration & dosage , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Pregnancy Complications , Pregnancy Outcome , Abatacept/administration & dosage , Abatacept/adverse effects , Abatacept/metabolism , Abnormalities, Drug-Induced/etiology , Adolescent , Adult , Age Factors , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Antirheumatic Agents/metabolism , Arthritis, Rheumatoid/physiopathology , Contraindications , Etanercept/administration & dosage , Etanercept/adverse effects , Etanercept/metabolism , Female , Fertility , Humans , Infliximab/administration & dosage , Infliximab/adverse effects , Infliximab/metabolism , Methotrexate/administration & dosage , Methotrexate/adverse effects , Milk, Human/metabolism , Pregnancy , Risk , Time Factors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Young Adult
10.
Mod Rheumatol ; 25(3): 393-400, 2015 May.
Article in English | MEDLINE | ID: mdl-25382730

ABSTRACT

OBJECTIVES: A nationwide survey was conducted to assess the number of patients, clinical aspects, treatment, and prognosis of adult Still's disease (ASD) in Japan. METHODS: A primary questionnaire was sent to randomly selected medical institutions in order to estimate the number of patients. We sent a secondary questionnaire to the same institutions to characterize the clinical manifestations and treatment of ASD. RESULTS: The estimated prevalence of ASD was 3.9 per 100,000. Analysis of 169 patients showed a mean age at onset of 46 years. The main clinical symptoms were fever, arthritis, and typical rash in agreement with previous surveys. Oral glucocorticoids were used to treat 96% of the patients, while methotrexate was used in 41% and biological agents were used in 16%. Lymphadenopathy and macrophage activation syndrome were significantly associated with increased risk of relapse (P < 0.05, each). Patients who achieved remission after tocilizumab therapy had significantly longer disease duration (6.2 years) than patients who did not (1.9 years) (p < 0.05). CONCLUSIONS: The 2010-2011 nationwide survey of ASD identified important changes in treatment and improvement of prognosis compared with previous surveys.


Subject(s)
Antirheumatic Agents/therapeutic use , Glucocorticoids/therapeutic use , Methotrexate/therapeutic use , Still's Disease, Adult-Onset/epidemiology , Adult , Age of Onset , Aged , Exanthema/drug therapy , Female , Fever/drug therapy , Humans , Japan/epidemiology , Male , Middle Aged , Prevalence , Prognosis , Remission Induction , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/drug therapy
11.
Intern Med ; 53(3): 263-7, 2014.
Article in English | MEDLINE | ID: mdl-24492698

ABSTRACT

We herein report the case of a Japanese man with polyarteritis nodosa (PAN) accompanied by multiple myeloma (MM). The patient was diagnosed with PAN. Concurrently, IgG kappa paraprotein was detected, and bone marrow changes indicative of MM were observed. Prednisolone (PSL) administered at a dose of 30 mg/day was initiated; however, the serum creatinine level increased. In spite of increasing the dose of PSL to 45 mg/day and initiating treatment with double filtration plasmapheresis, the patient's renal dysfunction continued to progress and haemodialysis was introduced. He died from pneumonia 12 months after admission. We conclude that renal failure is an important risk factor in the prognosis of PAN accompanied by MM.


Subject(s)
Acute Kidney Injury/complications , Acute Kidney Injury/diagnosis , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Polyarteritis Nodosa/complications , Polyarteritis Nodosa/diagnosis , Fatal Outcome , Humans , Male , Middle Aged
12.
Mod Rheumatol ; 24(1): 78-85, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24261762

ABSTRACT

OBJECTIVES: Pentraxin 3 (PTX3) plays an important role in inflammation, immunity, and atherosclerosis. Plasma PTX3 level has drawn attention as a marker that responds to local inflammation. Systemic lupus erythematosus (SLE), a chronic inflammatory disorder which can affect multiple organs, develops atherosclerosis prematurely. We examined the hypotheses that the concentration of plasma PTX3 increases in patients with SLE and that PTX3 is associated with the disease activity and premature atherosclerosis. METHODS: Plasma PTX3 concentrations were measured in 65 patients with SLE and 53 control subjects. The patients were also evaluated with respect to their clinical characteristics, disease activity indices, and corticosteroid therapy. We performed carotid ultrasonography to measure subclinical atherosclerosis in patients with SLE. RESULTS: Plasma PTX3 concentration of the SLE patients was significantly higher than that of the healthy controls (median 3.9 vs. 2.0 ng/mL, p < 0.001). In patients with SLE, PTX3 concentrations were correlated with SLEDAI (p = 0.011), BILAG index (p < 0.001), C-reactive protein (p < 0.001), anemia (p = 0.020), hypoalbuminemia (p = 0.022), and daily dose of prednisolone (p = 0.008) after adjustment for age and sex. PTX3 was not associated with disease duration, anti-ds DNA antibody, CH50, or carotid atherosclerosis. CONCLUSIONS: Patients with SLE have increased concentrations of PTX3 compared with control subjects. PTX3 was significantly associated with disease activity but not with carotid atherosclerosis.


Subject(s)
Atherosclerosis/blood , C-Reactive Protein/metabolism , Carotid Arteries/diagnostic imaging , Carotid Artery Diseases/blood , Lupus Erythematosus, Systemic/blood , Serum Amyloid P-Component/metabolism , Adult , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging , Carotid Artery Diseases/complications , Carotid Artery Diseases/diagnostic imaging , Female , Humans , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnostic imaging , Male , Middle Aged , Severity of Illness Index , Ultrasonography
13.
Mod Rheumatol ; 23(2): 269-75, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22584471

ABSTRACT

OBJECTIVE: Osteoprotegerin (OPG), a regulator of bone resorption, is involved in the pathogenesis of rheumatoid arthritis (RA) and atherosclerosis. OPG is elevated in patients with coronary artery disease, and high OPG levels are associated with cardiac disease severity and mortality in the general population. The purpose of this study was to investigate the relationship of serum OPG levels, traditional coronary risk factors, and RA-related factors to carotid atherosclerosis in RA patients. METHODS: Ninety-one RA patients were studied (85 % women, age 60 ± 10 years). Serum OPG levels were measured by an enzyme-linked immunosorbent assay. The prevalence of carotid plaque was assessed by ultrasonographic imaging in all patients. The relationship between various clinical characteristics, OPG, and carotid plaque was examined. RESULTS: Serum OPG levels were significantly higher in patients with carotid plaque than in those without plaque (median level 1,397 vs. 887 pg/mL, respectively; P = 0.006). There were no significant differences between RA patients with and without carotid plaque with respect to sex, duration of RA, blood pressure, body mass index, smoking, low-density lipoprotein cholesterol, Disease Activity Score-28, van der Heijde-modified Sharp score, and prednisolone dose. After adjusting for age, sex, and C-reactive protein, elevated levels of OPG were still associated with a higher prevalence of carotid plaque in patients with RA (P = 0.038). CONCLUSION: RA patients suffer from accelerated atherosclerosis and also have increased levels of OPG. The serum OPG level is independently associated with carotid plaque.


Subject(s)
Arthritis, Rheumatoid/blood , Atherosclerosis/blood , Carotid Artery Diseases/blood , Osteoprotegerin/blood , Plaque, Atherosclerotic/blood , Adult , Aged , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/diagnostic imaging , Atherosclerosis/complications , Atherosclerosis/diagnostic imaging , Carotid Artery Diseases/complications , Carotid Artery Diseases/diagnostic imaging , Female , Humans , Male , Middle Aged , Plaque, Atherosclerotic/complications , Plaque, Atherosclerotic/diagnostic imaging , Risk Factors , Ultrasonography
14.
Intern Med ; 51(19): 2825-30, 2012.
Article in English | MEDLINE | ID: mdl-23037484

ABSTRACT

We treated a 77-year-old woman with pleural and pericardial effusion and ascites. Initially, collagen vascular disease was suspected due to the presence of anti-centromere antibodies and suspected complication of pulmonary arterial hypertension. However, soft-tissue abnormalities surrounding the bilateral kidneys detected on computed tomography (CT) and symmetrical lesions of the long bones detected on bone scintigraphy made us consider a diagnosis of Erdheim-Chester disease (ECD), which is a rare form of histiocytosis. We immunochemically analyzed the cells derived from the ascites in detail and confirmed the diagnosis. Immunocytochemical analyses may therefore help to achieve a better understanding of the pathogenesis of this rare disease.


Subject(s)
Erdheim-Chester Disease/immunology , Erdheim-Chester Disease/pathology , Aged , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Ascites/immunology , Ascites/pathology , Bone and Bones/diagnostic imaging , Diagnosis, Differential , Erdheim-Chester Disease/diagnosis , Female , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Kidney/pathology , Magnetic Resonance Imaging , Radionuclide Imaging , Receptors, Cell Surface/metabolism , Tomography, X-Ray Computed
15.
Article in Japanese | MEDLINE | ID: mdl-23291482

ABSTRACT

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that mainly affects young women, a group usually free of atherosclerosis. As treatment for SLE has improved during recent years and long term survival increased, it has become clear that patients with SLE have increased morbidity and mortality from atherosclerotic cardiovascular disease. Several imaging techniques showed increased prevalence of premature atherosclerosis which was most striking in young patients with SLE. Pathogenesis of atherosclerosis is an inflammatory process. Inflammatory cells and mediators play a key role in the pathogenesis of atherosclerosis. Systemic inflammation and immune dysfunction are thought to accelerate atherosclerosis in patients with SLE as well. Several possible reasons for accelerated atherosclerosis in SLE have been suggested. Traditional coronary risk factors, other coronary risk factors including lipoprotein (a), CRP, homocysteine, inflammatory cytokines, increased vascular damage, lupus related factors and medications may affect the development of atherosclerosis in SLE. Atherosclerosis risk assessment, preventive strategy for accelerated atherosclerosis and its treatment would be required in patients with SLE.


Subject(s)
Coronary Artery Disease/etiology , Inflammation/complications , Lupus Erythematosus, Systemic/complications , C-Reactive Protein/metabolism , Coronary Artery Disease/epidemiology , Coronary Artery Disease/immunology , Coronary Artery Disease/prevention & control , Cytokines/physiology , Female , Homocysteine/blood , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Inflammation/immunology , Inflammation Mediators/physiology , Lipoprotein(a)/blood , Lupus Erythematosus, Systemic/immunology , Male , Randomized Controlled Trials as Topic , Risk Assessment , Risk Factors , Sex Factors
16.
J Biol Chem ; 286(17): 14963-71, 2011 Apr 29.
Article in English | MEDLINE | ID: mdl-21402704

ABSTRACT

Until recently, effector T helper (Th) cells have been classified into two subsets, Th1 and Th2 cells. Since the discovery of Th17 cells, which produce IL-17, much attention has been given to Th17 cells, mainly because they have been implicated in the pathogenesis of various inflammatory diseases. We have performed transcriptome analysis combined with factor analysis and revealed that the expression level of c-Maf, which is considered to be important for Th2 differentiation, increases significantly during the course of Th17 differentiation. The IL-23 receptor (IL-23R), which is important for Th17 cells, is among putative transcriptional targets of c-Maf. Interestingly, the analysis of c-Maf transgenic Th cells revealed that the overexpression of c-Maf did not lead to the acceleration of the early stage of Th17 differentiation but rather to the expansion of memory phenotype cells, particularly with Th1 and Th17 traits. Consistently, mouse wild-type memory Th cells expressed higher mRNA levels of c-Maf, IL-23R, IL-17, and IFN-γ than control cells; in contrast, Maf(-/-) memory Th cells expressed lower mRNA levels of those molecules. Thus, we propose that c-Maf is important for the development of memory Th cells, particularly memory Th17 cells and Th1 cells.


Subject(s)
Cell Differentiation/immunology , Immunologic Memory/genetics , Proto-Oncogene Proteins c-maf/genetics , Proto-Oncogene Proteins c-maf/physiology , Th17 Cells/cytology , Transcriptional Activation/immunology , Animals , Cell Proliferation , Gene Expression Profiling , Mice , Mice, Knockout , Proto-Oncogene Proteins c-maf/immunology , RNA, Messenger/analysis , Th1 Cells/immunology
17.
Clin Exp Rheumatol ; 29(1): 43-9, 2011.
Article in English | MEDLINE | ID: mdl-21345291

ABSTRACT

OBJECTIVES: We previously reported that 10 mg/day of simvastatin significantly reduced clinical scores of rheumatoid arthritis (RA) in active RA patients with hypercholesterolemia. In this study, we have investigated the mechanism by which simvastatin inhibits the production of the mediators of inflammation, such as pentraxin 3 (PTX3) and monocyte chemoattractant protein-1 (MCP-1), from fibroblast-like synoviocytes (FLS) derived from patients with RA. METHODS: FLS from RA patients were cultured with 0-10 µM simvastatin for 24 h. ELISA and real-time PCR were used to quantitate the protein level and the mRNA level of PTX3 and MCP-1, respectively. RESULTS: Simvastatin both reduced the secretion of PTX3 and MCP-1 in FLS cultures and inhibited their mRNA expression in these cells. The effects of simvastatin were all completely reversed in the presence of mevalonic acid or geranylgeranylpyrophosphate, but not in the presence of farnesyl-pyrophosphate. The geranylgeranyl transferase inhibitor GGTI-298 and the Rho kinase inhibitor Y-27632 inhibited the production of PTX3 but not of MCP-1. CONCLUSIONS: Although simvastatin inhibited the production of PTX3 and MCP-1 in RA FLS, the mechanisms were quite different. It inhibits PTX3 production in a Rho-dependent manner but MCP-1 production in a Rho-independent manner. These results shed light on novel aspects of the anti-inflammatory mechanisms of simvastatin and may prove its important role in the treatment of rheumatic diseases.


Subject(s)
Arthritis, Rheumatoid/drug therapy , C-Reactive Protein/metabolism , Chemokine CCL2/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Polyisoprenyl Phosphates/pharmacology , Serum Amyloid P-Component/metabolism , Simvastatin/pharmacology , Amides/pharmacology , Arthritis, Rheumatoid/pathology , Benzamides/pharmacology , C-Reactive Protein/antagonists & inhibitors , C-Reactive Protein/genetics , Cells, Cultured , Chemokine CCL2/antagonists & inhibitors , Chemokine CCL2/genetics , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression/drug effects , Humans , Mevalonic Acid/pharmacology , Pyridines/pharmacology , RNA, Messenger/metabolism , Serum Amyloid P-Component/antagonists & inhibitors , Serum Amyloid P-Component/genetics , Sesquiterpenes/pharmacology , Synovial Membrane/drug effects , Synovial Membrane/metabolism , Synovial Membrane/pathology
18.
Mod Rheumatol ; 20(2): 183-7, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19898918

ABSTRACT

We had a rheumatoid arthritis (RA) patient resistant to multiple drugs and who developed panniculitis due to etanercept treatment, then responded fairly well to rituximab. Intracellular staining of cytokines in the peripheral blood mononuclear cells before and after rituximab administration revealed that the cytokine production, representative of T-helper (Th)1-, Th2-, and Th17-type responses, decreased abruptly after the treatment. Interestingly, this timing coincided with that of the manifestation of the beneficial effect. This relationship may provide useful insight into the mechanism of action of the drug and hence about the pathogenesis of RA.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/metabolism , Cytokines/metabolism , Lymphocyte Subsets/metabolism , Antibodies, Monoclonal, Murine-Derived , CD4-CD8 Ratio , Female , Flow Cytometry , Humans , Middle Aged , Rituximab
19.
Arthritis Rheum ; 61(11): 1580-5, 2009 Nov 15.
Article in English | MEDLINE | ID: mdl-19877084

ABSTRACT

OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory disease associated with premature atherosclerosis. We hypothesized that mediators of inflammation associated with atherosclerosis in other populations (interleukin-6 [IL-6], tumor necrosis factor alpha [TNFalpha], serum amyloid A [SAA], vascular endothelial growth factor, neutrophil count, IL-1alpha, E-selectin, intercellular adhesion molecule 1 [ICAM-1], myeloperoxidase [MPO], matrix metalloproteinase 9, and vascular cell adhesion molecule 1) would be increased and associated with the severity of coronary atherosclerosis in patients with RA. METHODS: Clinical variables, concentrations of inflammatory mediators, and coronary artery calcification were measured in 169 patients with RA and 92 control subjects. Differences in concentrations of inflammatory mediators were compared using median quantile regression. The relationship of inflammatory mediators with the severity of coronary calcification in RA and control subjects was examined using proportional odds logistic regression, allowing for interaction with disease status. Models were adjusted for traditional cardiovascular risk factors. RESULTS: Median serum concentrations of IL-6, SAA, ICAM-1, E-selectin, TNFalpha, and MPO and peripheral blood neutrophil count were higher in patients with RA than controls (all P < 0.05), independent of Framingham risk score and diabetes mellitus (DM). IL-6 (main effect odds ratio [OR] 1.72; 95% confidence interval [95% CI] 1.12, 2.66) and TNFalpha (main effect OR 1.49; 95% CI 1.16, 1.90) concentrations were significantly associated with higher amounts of coronary calcium, independent of Framingham risk score and DM, and such main effects significantly differed from controls (P = 0.001 and 0.03 for interaction, respectively). CONCLUSION: TNFalpha and IL-6 are significantly associated with the severity of subclinical atherosclerosis, independent of Framingham risk score, in RA.


Subject(s)
Arthritis, Rheumatoid/epidemiology , Biomarkers/blood , Coronary Artery Disease/epidemiology , Inflammation Mediators/blood , Adult , Age of Onset , Aged , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/immunology , Coronary Artery Disease/blood , Coronary Artery Disease/immunology , E-Selectin/blood , Female , Humans , Intercellular Adhesion Molecule-1/blood , Interleukin-1alpha/blood , Interleukin-6/blood , Logistic Models , Male , Matrix Metalloproteinase 9/blood , Middle Aged , Neutrophils , Peroxidase/metabolism , Risk Factors , Serum Amyloid A Protein/metabolism , Tumor Necrosis Factor-alpha/blood , Vascular Endothelial Growth Factor A/blood
20.
Rheumatol Int ; 29(4): 459-61, 2009 Feb.
Article in English | MEDLINE | ID: mdl-18802706

ABSTRACT

We report a Japanese male patient with intractable rheumatoid arthritis (RA), in whom tacrolimus was effective ultimately. Five years before the admission he was diagnosed as RA, which was resistant to various disease-modifying anti-rheumatic drugs (DMARDs). Two years before, administration of infliximab was initiated although the medicine failed to control RA. In spite of the multiple joint replacement, the RA disease activity worsened. Tacrolimus (1.5 mg/day) was administered. Twenty-four weeks of tacrolimus treatment reduced the disease activity score for 28 joints-erythrocyte sedimentation rate from 7.44 to 3.65. Herein, we present a patient with RA, who was successfully treated by tacrolimus, and in whom infliximab was not effective. Tacrolimus may be one of the drugs for RA patients refractory to the conventional treatments including methotrexate or tumor necrosis factor inhibitors.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/therapy , Immunosuppressive Agents/therapeutic use , Tacrolimus/therapeutic use , Antirheumatic Agents/therapeutic use , Disease Progression , Drug Resistance , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Infliximab , Male , Middle Aged , Retreatment , Tacrolimus/administration & dosage , Tacrolimus/adverse effects , Treatment Outcome
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