New species of bone-eating worm Osedax from the abyssal South Atlantic Ocean (Annelida, Siboglinidae)

A new species of bone-eating annelid, Osedax braziliensis sp. n., found in a sunken whale carcass at a depth of 4,204 m at the base of the São Paulo Ridge in the South Atlantic Ocean off the Brazilian coast is described. The organism was retrieved using the human-occupied vehicle Shinkai 6500 during the QUELLE 2013 expedition. This is the 26th species of the genus and the first discovery from the South Atlantic Ocean, representing the deepest record of Osedax worldwide to date. This species morphologically resembles Osedax frankpressi but is distinguished by the presence of a yellow bump or patch behind the prostomium and its trunk length. Molecular phylogenetic analysis using three genetic markers (COI, 16S, and 18S) showed that O. braziliensis sp. n. is distinct from all other Osedax worms reported and is a sister species of O. frankpressi

Efficacy of mizoribine pulse therapy in patients with rheumatoid arthritis who show a reduced or insufficient response to infliximab

The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-α used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4–8, 12–16, and 20–24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12–16 and 20–24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12–16 and in five patients (50%) at weeks 20–24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics

Identification of novel biomarker as citrullinated inter-alpha-trypsin inhibitor heavy chain 4, specifically increased in sera with experimental and rheumatoid arthritis

BackgroundAnticitrullinated protein antibodies (ACPA) and citrullinated proteins play key roles in the pathogenesis of rheumatoid arthritis (RA). Many candidate citrullinated antigens have been identified in joints, but citrullinated proteins in sera are mostly uncertain in patients with RA. We explored the expression of citrullinated proteins in joints and sera of experimental arthritis, and we further investigated their specific expression correlated with the disease activity in patients with RA.MethodsCitrullinated protein expression in tissues was examined by IHC in peptide glucose-6-phosphate isomerase-induced arthritis (pGIA). Serum citrullinated proteins from pGIA were examined by Western blotting, and the sequence was identified by MS. With the same methods, serum citrullinated proteins were analyzed in patients with RA, primary Sjögren’s syndrome, systemic lupus erythematosus, and osteoarthritis as well as in healthy subjects, by Western blotting and MS. In patients with RA, the relationship between the expression of the identified protein (inter-alpha-trypsin inhibitor heavy chain 4 [ITIH4]) and clinical features was evaluated, and the levels of citrullinated ITIH4 were compared before and after biological treatment. The antibody response against citrullinated ITIH4 peptide was measured by enzyme-linked immunosorbent assay.ResultsCitrullinated proteins were detected specifically in arthritic joints and sera from pGIA relative to controls. In sera, a common band of citrullinated protein at 120 kDa was revealed, and it fluctuated in parallel with arthritis score of pGIA by Western blotting. Interestingly, in 82% of RA patient sera, similar bands of citrullinated protein were specifically detected. These proteins were identified as citrullinated ITIH4, and especially the R438 site was commonly citrullinated between mice and humans. Citrullinated ITIH4 levels were associated with clinical parameters such as C-reactive protein (CRP), rheumatoid factor, and Disease Activity Score in 28 joints as measured by CRP in patients with RA. Its levels were decreased in correlation with the reduction of disease activity score after effective treatment in patients with RA. Moreover, antibody response to citrullinated epitope in ITIH4 was specifically observed in patients with RA.ConclusionsOur results suggest that serum citrullinated ITIH4 was specifically increased in patients with RA and could be a novel biomarker for assessing disease activity in patients with RA

Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules

Objective: To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA). Method: This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patientyears (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan-Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied. Results: The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE. Conclusions: Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept

New species of bone-eating worm Osedax from the abyssal South Atlantic Ocean (Annelida, Siboglinidae)

http://www.godac.jamstec.go.jp/darwin/cruise/yokosuka/yk13-04_leg1/