Rheumatoid Arthritis: Maeno N

Maeno N, Takei S. · Department of Pediatrics, Faculty of Medicine, Kagoshima University. · Ryoikibetsu Shokogun Shirizu. · Pubmed #11269135 No free full text.

This publication has no abstract.

Yoshidome K, Takei S, Imanaka H, Maeno N, Ohkawa T, Kawano Y. · Department of Pediatrics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. · Pediatr Int. · Pubmed #15310311 No free full text.

Abstract: BACKGROUND: Mizoribine (MZR) is a novel immunosuppressant developed in Japan. As MZR is reported to be less toxic than other cytotoxic drugs, it is frequently used in Japan in the treatment of adult patients with rheumatoid arthritis or lupus nephritis. The objective of this study was to evaluate the efficacy of MZR in children with SLE. Nine female children with lupus nephritis who had undergone renal biopsy before starting MZR, were involved in this study. Their mean disease duration was 4.8 years at the time MZR treatment was initiated. Patients who had received intensive medications, such as methyl-prednisolone pulse therapy, intravenous cyclophosphamide pulse therapy, and/or other immunosuppressants, within the 4 months prior to the start of the study, were excluded. METHODS: Patients treated with 3 mg/kg per day of MZR were monitored every month for up to 1 year. The efficacy of MZR was evaluated by the changes from baseline values of serum C3, serum C4, anti-dsDNA antibody titer, erythrocyte sedimentation rate (ESR), urinary protein, dosage of prednisolone (PSL), and the sum of the scores defined by these parameters. RESULTS: Favorable changes were observed in C3 and ESR after 2 months and 3 months of MZR therapy, respectively. At 3 months of MZR therapy, the sum of scores defined by the parameters for disease activity indicated that MZR was more effective in non-class IV nephritis patients (n = 5) than in class IV nephritis patients (n = 4) (P = 0.0197). All nine children involved in the study tolerated the MZR therapy well during the study. CONCLUSION: MZR was safe in lupus children, but its efficacy was limited in patients with non-class IV nephritis. Further study is necessary, in which higher dosages and/or earlier use of MZR is provided to a larger number of children.

Nerome Y, Imanaka H, Nonaka Y, Tsuru Y, Maeno N, Takezaki T, Mori H, Akaike H, Kubota T, Kawano Y, Takei S. · Department of Pediatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. · Mod Rheumatol. · Pubmed #18273538 No free full text.

Abstract: We report a 27-year-old case of juvenile idiopathic arthritis (JIA) having been stopped infliximab during pregnancy. She was safely treated by infliximab therapy with premedications for preventing infusin reactions after her delivery, and then improved in the same manner as when she had been treated with infliximab therapy before pregnancy. As a result, it remains unclear whether or not we can use infliximab to control disease activities during pregnancy. In addition, it is also important to clarify whether or not premedications should be used when resuming infliximab treatment in such patients after pregnancy. These problems still remain controversial. More definitive data are needed in order to allow rheumatologists to better select the optimal TNF-alpha inhibitor therapy when treating pregnant JIA patients.

Sugiura T, Maeno N, Kawaguchi Y, Takei S, Imanaka H, Kawano Y, Terajima-Ichida H, Hara M, Kamatani N. · Institute of Rheumatology, Tokyo Women's Medical University School of Medicine, 10-22 Kawada-cho, Shinjuku-ku, Tokyo, Japan. · Arthritis Res Ther. · Pubmed #16563174 links to  free full text

Abstract: Recently, we reported that genetic polymorphisms within the human IL18 gene were associated with disease susceptibility to adult-onset Still's disease (AOSD), which is characterized by extraordinarily high serum levels of IL-18. Because high serum IL-18 induction has also been observed in the systemic type of juvenile idiopathic arthritis (JIA), we investigated whether similar genetic skewing is present in this disease. Three haplotypes, S01, S02, and S03, composed of 13 genetic polymorphisms covering two distinct promoter regions, were determined for 33 JIA patients, including 17 with systemic JIA, 10 with polyarthritis, and 6 with oligoarthritis. Haplotypes were also analyzed for 28 AOSD patients, 164 rheumatoid arthritis (RA) patients, 102 patients with collagen diseases, and 173 healthy control subjects. The frequency of individuals carrying a diplotype configuration (a combination of two haplotypes) of S01/S01 was significantly higher in the JIA patients, including all subgroups, than in the healthy controls (P = 0.0045, Fischer exact probability test; odds ratio (OR) = 3.55, 95% confidence interval (CI) = 1.55-8.14). In patients with systemic JIA, its frequency did not differ statistically from that of normal controls. Nevertheless, it is possible that haplotype S01 is associated with the phenotype of high IL-18 production in systemic JIA because the patients carrying S01/S01 showed significantly higher serum IL-18 levels compared with patients with other diplotype configurations (P = 0.017, Mann-Whitney U test). We confirmed that the frequency of the diplotype configuration of S01/S01 was significantly higher in AOSD patients than in healthy control subjects (P = 0.011, OR = 3.45, 95% CI = 1.42-8.36). Furthermore, the RA patients were also more predisposed to have S01/S01 (P = 0.018, OR = 2.00, 95% CI = 1.14-3.50) than the healthy control subjects, whereas the patients with collagen diseases did not. In summary, the diplotype configuration of S01/S01 was associated with susceptibility to JIA as well as AOSD and RA, and linked to significantly higher IL-18 production in systemic JIA. Possession of the diplotype configuration of S01/S01 would be one of the genetic risk factors for susceptibility to arthritis in the Japanese population.

Maeno N, Takei S, Imanaka H, Yamamoto K, Kuriwaki K, Kawano Y, Oda H. · Department of Infection and Immunity, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima, Japan. · Arthritis Rheum. · Pubmed #15188370 links to  free full text

Abstract: The aberrant induction of proinflammatory cytokines is considered to be crucial in the pathogenesis of systemic juvenile idiopathic arthritis and adult-onset Still's disease. Interleukin-18 (IL-18) in particular has been reported to be a candidate for the key cytokine in both diseases; however, the origin of IL-18 is unclear. To clarify the origin, we investigated specimens from various organs obtained during autopsy of a child with systemic JIA and macrophage activation syndrome, using immunohistochemical staining. Our results showed a high number of cells expressing IL-18 in the bone marrow but not in the other organs. This finding suggests that bone marrow is the origin of increased serum IL-18 and raises the possibility that other proinflammatory cytokines are also induced by IL-18 in bone marrow in this disease. Bone marrow may be an essential organ in the pathogenesis of systemic JIA.

Ruperto N, Buratti S, Duarte-Salazar C, Pistorio A, Reiff A, Bernstein B, Maldonado-Velázquez MR, Beristain-Manterola R, Maeno N, Takei S, Falcini F, Lepore L, Spencer CH, Pratsidou-Gertsi P, Martini A, Ravelli A. · Università di Genova, Istituto di Ricovero e Cura a Carattere Scientifico G. Gaslini, Genoa, Italy. · Arthritis Rheum. · Pubmed #15188334 links to  free full text

Abstract: OBJECTIVE: To assess the health-related quality of life (HRQL) of patients with juvenile-onset systemic lupus erythematosus (JSLE) and its relationship with disease activity and accumulated damage. METHODS: In this cross-sectional study, HRQL was assessed using the Child Health Questionnaire (CHQ), disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and accumulated damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). RESULTS: A total of 297 patients were included. The mean +/- SD physical and psychosocial summary scores of the CHQ were 40.2 +/- 15.0 and 44.8 +/- 10.7, respectively. The most impaired CHQ subscales were global health, general health perceptions, and parent impact-emotional. The SLEDAI score was significantly correlated with both the physical summary score (r = -0.29, P < 0.0001) and psychosocial summary score (r = -0.25, P < 0.0001), whereas the SDI score was significantly correlated only with the physical summary score (r = -0.23, P = 0.0001). CONCLUSION: We found that patients with JSLE have significant impairment of their HRQL, particularly in the physical domain. HRQL may be affected by both disease activity and accumulated damage, particularly in the renal, central nervous, and musculoskeletal systems.

Maeno N, Takei S, Fujikawa S, Yamada Y, Imanaka H, Hokonohara M, Kawano Y, Oda H. · Department of Bacteriology and the Department of Pediatrics, Faculty of Medicine, Kagoshima University, Kagoshima, Japan. · J Rheumatol. · Pubmed #15170938 No free full text.

Abstract: 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. RESULTS: The average serum concentration of antiagalactosyl IgG antibodies for healthy controls was 2.41 +/- 0.93 arbitrary units (AU)/ml, and the cutoff value of the normal range was set at 4.3 AU/ml (mean + 2 SD). As a result, antiagalactosyl IgG antibodies were positive in 25 (37%) of 68 patients with JIA, and 14 (93%) of 15 patients with juvenile onset SS, in whom values were much higher than the frequencies of RF positivity. The serum concentrations of antiagalactosyl IgG antibodies in patients were closely correlated with those of RF. Thirteen patients with JIA and 6 patients with juvenile onset SS were positive for antiagalactosyl IgG antibodies despite being negative for RF. With regard to prognosis during followup periods of at least 5 years, JIA patients positive for antiagalactosyl IgG antibodies, even if negative for RF, were resistant to treatment. However, positivity for antiagalactosyl IgG antibodies had no relation to joint destruction. CONCLUSION: Our data suggest that antiagalactosyl IgG antibodies, compared with RF, show higher sensitivity to detect immunological disorders in JIA and juvenile onset SS.

Shigemori M, Takei S, Imanaka H, Maeno N, Hokonohara M, Miyata K. · Department of Pediatrics, Faculty of Medicine, Kagoshima University, Kagoshima University, Japan. · Pediatr Int. · Pubmed #12139564 No free full text.

Abstract: BACKGROUND: We have previously reported that serum levels of hyaluronic acid (HA) objectively reflect the severity of arthritis in juvenile rheumatoid arthritis (JRA). However, clear diagnostic standards do not exist for JRA; it is difficult to evaluate arthritis in children, particularly in small children and the diagnostic criteria for JRA requires an exclusion of several diseases. Therefore, if a specific test finding associated with JRA could be established, it would enable general pediatricians to make an objective diagnosis. METHODS: We measured the serum HA levels in children with joint symptoms as a chief complaint. The total number of subjects were 197 children; of these 89 had JRA, 39 had rheumatic diseases other than JRA, and 69 had non-rheumatic diseases (including systemic 31, polyarticular 40 and pauci-articular in 17), rheumatic diseases other than JRA in 39 subjects, and non-rheumatic diseases in 69 subjects. Sandwich enzyme-linked immunosorbent assay measured HA by using the HA binding protein. RESULTS: The serum level of HA was significantly higher in systemic and polyarticular JRA patients than in patients with pauci-articular JRA, with rheumatic diseases other than JRA, and non-rheumatic patients. With a cut-off value of 100 ng/mL, a diagnostic value of HA in all JRA patients was 48.3% sensitivity and 98.1% specificity. CONCLUSIONS: In children presenting with joint symptoms, serum HA measurement is useful for diagnosing systemic and polyarticular JRA.

Nerome Y, Imanaka H, Maeno N, Mori H, Akaike H, Shigemori M, Takei S, Hokonohara M, Miyata K. · Deprtment of Pediatrics and School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima-city. · Ryumachi. · Pubmed #11729665 No free full text.

Abstract: In Sjögren syndrome, purpura is one of its various well known eruptions. Although this disease state is assumed to be based on hypergammaglobulinemia, the details of its mechanism are unknown. We experienced a case involving a female patient with primary Sjögren syndrome showing repeated purpura on the legs, and examined her blood viscosity and histopathology. This girl developed Sjögren syndrome and was admitted to our hospital at 12-years-old. She underwent steroid treatment because of aggravation of the xerosis state and prominent purpura on the legs. Hypergammaglobulinemia was improved during the course; however, purpura appeared repeatedly. Although her blood viscosity was slightly higher than normal, this had no relation to purpura and serum gamma globulin values. Skin biopsy revealed necrotizing angiitis. These results suggest that the purpura of this case was caused not only by hyperviscosity from the hypergammaglobulinemia but also involvement of vasculitis by the primary disease.

Maeno N, Takei S, Imanaka H, Oda H, Yanagi K, Hayashi Y, Miyata K. · Department of Pediatrics, Faculty of Medicine, Kagoshima University, Kagoshima City, Japan. · J Rheumatol. · Pubmed #11327263 No free full text.

Abstract: OBJECTIVE: To investigate the prevalence of anti-alpha-fodrin antibody specific for adult Sjögren's syndrome (SS) in patients with juvenile onset SS. METHODS: Serum anti-alpha-fodrin antibody was examined in 15 patients with juvenile SS (11 cases of primary SS and 4 secondary SS) and in 16 children with systemic lupus erythematosus (SLE) by Western blot analysis using a recombinant 120 kDa alpha-fodrin fusion protein. RESULTS: All the 15 serum samples from patients with SS reacted with a recombinant alpha-fodrin fusion protein in Western blot analysis. In contrast, reactivity was found in only 2 of the 16 patients with SLE. The clinical features of the 15 patients with juvenile onset SS were very specific; only 4 patients complained of dryness, while 6 had abnormal excretion ability. Salivary gland enlargement was the most common clinical manifestation. Characteristic laboratory findings in juvenile onset SS included a higher prevalence of antinuclear antibodies, anti-SSA/Ro antibodies, and rheumatoid factor, as well as increased erythrocyte sedimentation rate and hypergammaglobulinemia. CONCLUSION: The pathogenesis of juvenile SS seems to be the same as that of adult SS, although subjective symptoms of dryness are less frequent in juvenile cases. This discrepancy may indicate that SS is a slowly progressive disease with a long time span. The anti-alpha-fodrin antibody is likely to be a reliable diagnostic marker for juvenile SS.

Maeno N, Takei S, Imanaka H, Takasaki I, Kitajima I, Maruyama I, Matsuo K, Miyata K. · Department of Pediatrics, Faculty of Medicine, Kagoshima University, Kagoshima City, Japan. · J Rheumatol. · Pubmed #10529148 No free full text.

Abstract: OBJECTIVE: To investigate the relevance of vascular endothelial growth factor (VEGF) in the pathogenesis of juvenile rheumatoid arthritis (JRA). METHODS: Serum VEGF levels in 58 patients with JRA (systemic in 17, polyarticular in 29, pauciarticular in 12) were measured by ELISA and compared with those of 21 patients with infectious diseases and 50 healthy children. Correlations of VEGF levels with number of joints with active arthritis, erythrocyte sedimentation rate (ESR), and hyaluronic acid (HA) were examined. RESULTS: Serum levels of VEGF in patients with JRA were significantly higher than in healthy controls. Patients with systemic and polyarticular JRA showed statistically higher levels of VEGF than those with infectious diseases. VEGF levels correlated statistically with C-reactive protein (CRP) in patients with both infectious diseases and polyarticular JRA, but the regression slope (VEGF/CRP) was much steeper in polyarticular JRA than in infectious diseases. Serum VEGF levels correlated with disease activity variables such as the number of joints with active arthritis, ESR, and serum HA levels in polyarticular JRA. CONCLUSION: The correlation of serum VEGF levels and disease activity in polyarticular JRA suggests that VEGF may take an active part in joint inflammation.

Maeno N, Takei S, Nomura Y, Imanaka H, Hokonohara M, Miyata K. · No affiliation provided · Arthritis Rheum. · Pubmed #12355506 links to  free full text

This publication has no abstract.