Subject(s)
Antibodies, Monoclonal, Humanized , Glucocorticoids , Still's Disease, Adult-Onset , Humans , Still's Disease, Adult-Onset/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Glucocorticoids/therapeutic use , Male , Adult , Female , Middle Aged , Treatment Outcome , Antirheumatic Agents/therapeutic use , Acute DiseaseSubject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Azetidines , Lung Diseases, Interstitial , Purines , Pyrazoles , Humans , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Lung Diseases, Interstitial/drug therapy , Lung Diseases, Interstitial/etiology , Azetidines/therapeutic use , Sulfonamides/therapeutic use , Antirheumatic Agents/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: Clinically amyopathic dermatomyositis (CADM) patients frequently develop refractory interstitial lung disease (ILD), with a poor prognosis. We aimed to verify the efficacy and safety of plasma exchange (PE) treatment for ILD in CADM. METHOD: A retrospective case-control study was conducted to compare clinical outcomes with and without PE treatment in CADM-ILD patients refractory to combination therapy of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide. Among 19 enrolled patients, 11 were further treated with PE. We compared survival rates and other clinical characteristics. PE consisted of either fresh-frozen plasma or albumin as a replacement solution. RESULTS: Basal clinical characteristics at diagnosis, including age, gender, serum ferritin, Krebs von den Lungen-6 (KL-6), C-reactive protein, and respiratory function tests, did not differ between the two groups. The survival rate for treatment with PE was higher than for treatment without PE (91% and 50%, respectively, p < 0.05). Among PE-treated patients, anti-melanoma differentiation-associated gene-5 (anti-MDA-5) antibody titre, ferritin, and KL-6 as serological activity markers were sustainably reduced only after initiating PE. Therapeutic intervention with PE reduced the frequency of exacerbation of ILD requiring methylprednisolone pulse therapy. The occurrence of bacterial, fungal, and cytomegalovirus infection did not differ between the groups with and without PE, and adverse events associated with PE resolved with appropriate intervention. CONCLUSION: Combination therapy with PE was associated with an improved survival rate, and may be effective for the management of refractory ILD in CADM patients. A personalized therapeutic strategy including PE could be introduced for fatal rapidly progressive ILD.
Subject(s)
Lung Diseases, Interstitial , Plasma Exchange , Humans , Retrospective Studies , Case-Control Studies , Autoantibodies , Disease Progression , Lung Diseases, Interstitial/diagnosis , FerritinsSubject(s)
Arthritis, Rheumatoid/drug therapy , Myelitis/diagnostic imaging , Piperidines/adverse effects , Protein Kinase Inhibitors/adverse effects , Pyrimidines/adverse effects , Varicella Zoster Virus Infection/diagnostic imaging , Aged , Female , Humans , Magnetic Resonance Imaging , Myelitis/virology , Piperidines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Varicella Zoster Virus Infection/etiologySubject(s)
Lupus Erythematosus, Systemic/complications , Mycophenolic Acid/administration & dosage , Plasma Exchange/methods , Steroids/administration & dosage , Thrombotic Microangiopathies/drug therapy , ADAMTS13 Protein/genetics , Adult , Combined Modality Therapy , Female , Humans , Kidney/pathology , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Young AdultSubject(s)
Amino Acyl-tRNA Synthetases/immunology , Ferritins/blood , Iron Metabolism Disorders , Myositis , Neoplasms , Adult , Antibodies, Neoplasm/blood , Cytokines/blood , Disease Management , Female , Follow-Up Studies , Humans , Iron Metabolism Disorders/blood , Iron Metabolism Disorders/complications , Iron Metabolism Disorders/physiopathology , Iron Metabolism Disorders/therapy , Japan , Male , Middle Aged , Myositis/blood , Myositis/complications , Myositis/diagnosis , Myositis/etiology , Myositis/therapy , Neoplasms/classification , Neoplasms/complications , Neoplasms/immunology , Oncogene Proteins/immunologyABSTRACT
PURPOSE: Interleukin-32 (IL-32) is an inflammatory cytokine that is associated with the pathogenesis of several connective tissue diseases. We measured serum IL-32γ concentrations of systemic lupus erythematosus (SLE) patients. METHODS: Serum samples were obtained from SLE patients (n = 51), and healthy controls (n = 15). Serum IL-32 concentrations were measured using ELISA. Clinical information was obtained from medical records. RESULTS: Serum IL-32γ was detectable in three cases of SLE patients, whereas it was not detected in any healthy controls. Case 1: a 44-year-old female with lupus nephritis (LN) (Class II) and antiphospholipid antibody syndrome. Serum IL-32γ was 5.1 pg/ml. Case 2: a 30-year-old female with a history of diffuse proliferative LN (Class IV G (A/C)) and pulmonary hemorrhage. Serum IL-32γ was 8.9 pg/ml. Case 3: a 45-year-old female with chronic LN. Serum IL-32γ was 9.1 pg/ml. All three cases of IL-32γ-detectable patients had histories of LN and one had an active disease. In the context of LN, serum IL-32γ was detectable in 18.8% (three of 16) of SLE patients with histories of LN. CONCLUSION: We suppose that IL-32γ could contribute to the pathogenesis of renal diseases in some LN patients.
Subject(s)
Interleukins/blood , Lupus Erythematosus, Systemic/physiopathology , Lupus Nephritis/physiopathology , Adult , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lupus Erythematosus, Systemic/blood , Lupus Nephritis/blood , Male , Middle AgedABSTRACT
Subacute cerebellar ataxia in combination with cerebellar atrophy has rarely been reported as one of the manifestations of lupus in the central nervous system (CNS). We describe a 27-year-old woman with systemic lupus erythematosus who developed subacute cerebellar ataxia. Computed tomography and magnetic resonance imaging of her brain showed cerebellar atrophy in both hemispheres, particularly on the right side. Moreover, increased antineuronal cell antibody levels were detected in her cerebrospinal fluid. The cerebellar ataxia improved markedly following high-dose corticosteroid administration. This suggests that a relationship exists between autoantibodies and subacute atrophic processes in CNS lupus.
Subject(s)
Autoantibodies/cerebrospinal fluid , Cerebellar Ataxia/etiology , Cerebellar Diseases/etiology , Lupus Erythematosus, Systemic/complications , Adult , Atrophy , Cerebellar Ataxia/immunology , Cerebellar Ataxia/pathology , Cerebellar Diseases/immunology , Cerebellar Diseases/pathology , Dose-Response Relationship, Drug , Female , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Humans , Lupus Erythematosus, Systemic/immunology , Lupus Vasculitis, Central Nervous System/diagnosis , Lupus Vasculitis, Central Nervous System/drug therapy , Lupus Vasculitis, Central Nervous System/immunology , Magnetic Resonance Imaging , Tomography, X-Ray ComputedSubject(s)
Asthma/drug therapy , Bronchodilator Agents/therapeutic use , Eosinophils/drug effects , Forced Expiratory Volume/drug effects , Scopolamine Derivatives/therapeutic use , Aged , Asthma/immunology , Cohort Studies , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Sputum/cytology , Sputum/immunology , Tiotropium BromideABSTRACT
(18)F-2-deoxy-2-fluoro-glucose Positron Emission Tomography (FDG-PET) has been recently proposed as a promising cancer-screening test. However, the validity of FDG-PET in cancer screening has not been evaluated. We investigated the sensitivity of FDG-PET compared with upper gastric endoscopy in gastric cancer screening for asymptomatic individuals. A total of 2861 consecutive subjects (1600 men and 1261 women) who were asymptomatic and who underwent both FDG-PET and upper gastrointestinal endoscopy between 1 February 2004 and 31 January 2005 were included in this study. Both endoscopists and a radiologist were unaware of the results of the other diagnostic tests. The FDG-PET images were examined using criteria determined by the pattern of FDG accumulation. Sensitivity and specificity of FDG-PET were calculated compared with endoscopic diagnosis as the gold standard. Among 2861 subjects enrolled in the study, there were 20 subjects with gastric cancer, of whom 18 were T1 in depth of cancer invasion. Positive FDG-PET results were obtained only in 2 of the 20 cancer subjects. The calculated sensitivity and specificity for overall gastric cancers were 10.0% (95% confidence interval (CI): 1.2-31.7%) and 99.2% (95% CI: 98.8-99.5%), respectively. (18)F-2-deoxy-2-fluoro-glucose Positron Emission Tomography was poorly sensitive for detection of gastric cancer in the early stages.
Subject(s)
Endoscopy, Gastrointestinal/methods , Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Stomach Neoplasms/diagnosis , Aged , Female , Humans , Male , Mass Screening/methods , Middle Aged , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Maturity-onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes mellitus that is characterized by impairment of glucose-stimulated insulin secretion from pancreatic beta-cells. We previously reported that heterozygous mutations of the hepatocyte nuclear factor (HNF)-1alpha gene cause a form of MODY (MODY3). We have subsequently found that collectrin, a recently cloned kidney-specific gene of unknown function, is a novel target of HNF-1alpha in pancreatic beta-cells. In addition, we have demonstrated that collectrin forms a complex with the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex by direct interaction with snapin, a protein that is thought to be involved in neurotransmission by binding to synaptosomal-associated protein, 25 KD (SNAP25). Collectrin favours the formation of SNARE complexes and controls insulin exocytosis.
Subject(s)
Diabetes Mellitus, Type 2/metabolism , Hepatocyte Nuclear Factor 1-alpha/metabolism , Insulin-Secreting Cells/metabolism , Membrane Glycoproteins/metabolism , SNARE Proteins/metabolism , Animals , Disease Models, Animal , Exocytosis/physiology , Humans , Insulin/metabolism , Insulin Secretion , Mice , MutationABSTRACT
The inflammatory cytokine cascade plays a pivotal role in the pathogenesis of rheumatoid arthritis. Recently, a novel human cytokine, interleukin-32, was reported to induce tumor necrosis factor (TNF)-alpha. Interleukin-32 is expressed primarily in lymphoid tissues and leukocytes, but also in stimulated epithelial cells and synovial fibroblasts. Although the interleukin-32 receptor has not been reported, interleukin-32 can induce other inflammatory cytokines such as TNF-alpha, interleukin-1beta, and interleukin-6 from monocytes/macrophages in vitro and in vivo, and it synergizes with signals from pattern-recognition receptors. Notably, in the inflamed synovial tissues from rheumatoid arthritis patients, interleukin-32 is prominently expressed and correlates with the severity of arthritis and the expression of other cytokines, including TNF-alpha and interleukin-1. In experimental mice models of arthritis, joint injection of interleukin-32 induces joint inflammation, and overexpression of interleukin-32beta in hematopoietic cells exacerbates collagen-induced arthritis. Interleukin-32 can thus be seen to play an important role in the pathogenesis of rheumatoid arthritis.