Efficacy of Adalimumab in a Girl with Refractory Intestinal Behcet's Disease.

We describe our experience with a juvenile patient who had refractory intestinal Behcet's disease that responded to adalimumab, a fully humanized antibody against soluble TNF-α and its receptor. The patient, a 13-year-old girl, presented with oral aphthous ulcers, vulvar pain, and rashes on the lower extremities. She gradually developed a low-grade fever, abdominal pain, diarrhea, and hematochezia.

Long-term outcome of 114 adult JIA patients in a non-pediatric rheumatology institute in Japan.

Objective: To evaluate the long-term outcome of patients with juvenile idiopathic arthritis (JIA) using data from a large cohort database, Institute of Rheumatology, Rheumatoid Arthritis, managed by the Tokyo Women's Medical University.

Methods: Of 182 patients identified from the database from 2000 to 2013, 114 were verified as having JIA. The transition of medical care and the contributions of biological DMARDs were evaluated.

A nationwide survey of Aicardi-Goutières syndrome patients identifies a strong association between dominant TREX1 mutations and chilblain lesions: Japanese cohort study.

Objectives: Aicardi-Goutières syndrome (AGS) is a rare, genetically determined, early onset progressive encephalopathy associated with autoimmune manifestations. AGS is usually inherited in an autosomal recessive manner. The disease is rare, therefore the clinical manifestations and genotype-phenotype correlations, particularly with regard to autoimmune diseases, are still unclear.

Guidance on the use of adalimumab for juvenile idiopathic arthritis in Japan.

Adalimumab is a monoclonal antibody produced by DNA recombination technology, and is the first human monoclonal antibody against human tumor necrosis factor (TNF)-α in the world. Adalimumab binds with high affinity and specificity to soluble TNF-α and normalizes its biological action. The clinical development of adalimumab started in Europe.

Guidance on using tocilizumab for juvenile idiopathic arthritis.

Medical care for rheumatic disease in children has been supported by advances in rheumatology. In the past few years and based on knowledge about cytokines, particularly marked advances have been made in treatments using biological products. The fact that patients showed a marked response to treatment with biological products also provided uniform direction to treatment choice, which had previously been chaotic.

Guidelines on the use of etanercept for juvenile idiopathic arthritis in Japan.

Etanercept is a dimeric fusion protein consisting of the extracellular domain of human tumor necrosis factor receptor II (TNFR II, molecular weight 75 kDa) coupled to the Fc region of human immunoglobulin (IgG1). It is produced by recombinant DNA technology by first introducing the gene into Chinese hamster ovarian cells and then purifying the protein from the culture supernatant. The mechanism of action of etanercept consists of binding to serum TNF-alpha and lymphotoxin (LT)-alpha (TNF-beta), which prevents TNF-alpha and LT-alpha from binding to the TNF-alpha receptor on the plasma membrane of the target cell.

Methotrexate for the treatment of juvenile idiopathic arthritis: process to approval for JIA indication in Japan.

Methotrexate (MTX), the primary treatment for the articular-type juvenile idiopathic arthritis (JIA), is effective and brings about radiological improvement. Patient compliance is good, and it is recognized that its known side effects, namely, disruption of liver function and induction of pulmonary lesions, are unlikely to be severe at the low MTX doses that are administered. In Japan, MTX was granted approval in 1999 by the then Ministry of Health and Welfare specifically for treating rheumatoid arthritis in adult patients, allowing it be generally used in medical institutions for patients having National Health Insurance.

Proposal for juvenile idiopathic arthritis guidance on diagnosis and treatment for primary care pediatricians and nonpediatric rheumatologists (2007).

The Pediatric Standing Committee of the Japan College of Rheumatology, in collaboration with the Pediatric Rheumatology Association of Japan, produced guidance on the diagnosis and treatment for juvenile idiopathic arthritis (JIA) for primary care pediatricians and nonpediatric rheumatologists in Japan. This guidance aims to achieve early diagnosis and treatment for JIA, which is similar to adult rheumatoid arthritis (RA), based on recent progress in rheumatology, and to resolve arthritis at an early stage and improve the prognosis of the affected inflammatory joints. It describes clinical symptoms and laboratory findings characteristic to JIA in order to make early diagnosis and treatment possible, and also serves as a triage of patients who are refractory to the treatment protocol described here and need more aggressive interventions.

Antiagalactosyl IgG antibodies in juvenile idiopathic arthritis, juvenile onset Sjögren's syndrome, and healthy children.

Objective: To determine the normal range of antiagalactosyl IgG antibodies in healthy children, and to investigate the utility of determination of antiagalactosyl IgG antibodies in patients with juvenile idiopathic arthritis (JIA) and juvenile onset Sjögren's syndrome (SS).

Methods: Serum concentrations of antiagalactosyl IgG antibodies were measured in 225 healthy children, 68 patients with JIA (systemic arthritis in 21, polyarthritis in 29, oligoarthritis in 18), and 15 patients with juvenile onset SS, using a lectin-enzyme immunoassay employing prepared human agalactosyl IgG as antigen. A comparison was made between the prevalence and utility of antiagalactosyl IgG antibodies in patients and those of conventional rheumatoid factors (RF) determined by laser nephelometry.

Sendai virus vector-mediated gene transfer of glial cell line-derived neurotrophic factor prevents delayed neuronal death after transient global ischemia in gerbils.

We have developed a cytoplasmic replicating virus vector of Sendai virus (SeV) that infects and replicates in most mammalian cells, including neurons, and directs high-level gene expression. To investigate the protective effect of SeV vector-mediated gene transfer of glial cell line-derived neurotrophic factor (GDNF) on the delayed neuronal death caused by transient global ischemia in gerbils, SeV vectors carrying either GDNF (SeV/GDNF) or enhanced green fluorescent protein gene (SeV/GFP) were stereotaxically microinjected into the lateral ventricle. Four days after injection, occlusion of the bilateral common carotid arteries for 5 min produced transient global forebrain ischemia.

Hyperzincemia with systemic inflammation: a heritable disorder of calprotectin metabolism with rheumatic manifestations?

A boy had infantile-onset systemic inflammation, growth failure, hepatosplenomegaly, anemia, leukocytopenia, progressive muscular dystrophy, and hypercalprotectinemia, resulting in marked hyperzincemia. His mother had a history of chronic arthritis since childhood and also showed hypercalprotectinemia/hyperzincemia. We postulate an inherent defect in calprotectin metabolism.