Functional Loss of the HTLV-I Tax Protein Encoded by Variant Proviruses in Infected Individuals.

Accumulating evidence has indicated the presence of HTLV-I quasispecies in infected individuals. To elucidate their biological consequences, we amplified the whole Tax open reading frame (ORF) of HTLV-I proviruses by nested PCR from six infected individuals, including three HAM/TSP patients, and a cloned HTLV-I DNA, pMT2, and the products were introduced into an expression vector. The potential for transcriptional transactivation of protein products of independent 20-39 tax clones derived from each sample was evaluated by transfecting into pA18G-BHK-21 cells containing the HTLV-I LTR-driven lacZ gene. While all of 30 clones derived from pMT2 gave positive results, significant proportions, ranged between 16.0 and 35.0%, of the tax clones from the infected indiv iduals were functionally defective. The functional loss of these tax clones was confirmed by chloramphenicol acetyltransferase (CAT) assay in cells cotransfected with an HTLV-I LTR-CAT reporter. DNA sequence analysis revealed that the defective clones contained at least one nonsynonymous nucleotide substitutions from the consensus sequences of the individual. These findings strongly suggested that the accumulation of HTLV-I proviruses with defective tax was a common feature among infected individuals. Since the Tax protein is indispensable for viral replication, these defective viruses were likely to be generated in individuals after the event of infection. It is conceivable that the quasispecies plays a key role in the latency of HTLV-I infection and possibly in HTLV-I-related pathogenesis

Characteristics of late-onset spondyloarthritis in Japan: A retrospective cohort study

Spondyloarthritis may be increasingly present in older patients as life expectancy increases. We investigated clinical differences between early-onset and late-onset spondyloarthritis in Japan.We retrospectively reviewed 114 patients consecutively diagnosed with spondyloarthritis. The clinical course of each patient was observed for ?1 year. We defined early-onset and late-onset spondyloarthritis as <57 or ?57 years at a median age of this study group,respectively. We compared clinical characteristics between these 2 groups.Disease duration was significantly shorter before diagnosis in the late-onset group (P?<?.01). Inflammatory back pain (IBP) was significantly more common in the early-onset group (P?<?.01), whereas dactylitis frequency was significantly higher in the late-onset group. Significantly more patients with early-onset spondyloarthritis were human leukocyte antigen (HLA) B27-positive (P?<?.01). Articular synovitis, particularly of the wrist, was significantly more common on power Doppler ultrasound (PDUS) in the late-onset group (P?<?.01). Tenosynovitis or peritendinitis, particularly in the finger and wrist flexors were also more frequent in the late-onset group (P?<?.001 and P?<?.05, respectively). Enthesitis of the finger collateral ligament and lateral collateral ligament were significantly more common in the late-onset group (both P?<?.05). Multiple logistic regression analysis revealed that, comparatively, IBP was significantly and independently much more likely to occur in the early-onset group.The patients with late-onset spondyloarthritis had a lower frequency of IBP and HLA B27 and a higher frequency of dactylitis and PDUS findings in peripheral involvement

Real-world comparative effectiveness and safety of tofacitinib and baricitinib in patients with rheumatoid arthritis

Objective: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting.Methods: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks.Results: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, −0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated.Conclusions: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings

Prediction of DAS28-ESR remission at 6 months by baseline variables in patients with rheumatoid arthritis treated with etanercept in Japanese population

We tried to determine which baseline variables are responsible for remission induction at 6 months in unselected rheumatoid arthritis (RA) patients of Japanese population treated with etanercept. One hundred forty-one patients with RA who were administered etanercept were registered. Thirty-four patients were started on etanercept monotherapy, 60 patients on cotherapy with methotrexate (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy). None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR remission at 6 months. We examined association of gender, DAS at baseline, MTX cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at baseline with achievement of remission at 6 months by logistic regression analysis. All subjects were classified as having high (N = 109) or moderate disease activity (N = 32) at entry. One hundred twenty out of 141 patients (85.1%) continued treatment with etanercept at 6 months. Continuation rate was statistically higher in MTX cotherapy (93.3%) compared with etanercept monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%). Logistic regression analysis identified that MTX cotherapy at entry and moderate disease activity at entry were independent variables for remission induction at 6 months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with etanercept monotherapy. In this study of unselected patients, use of MTX and moderate disease activity at entry were associated with higher likelihood of response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA patients administrated etanercept who are intolerant to MTX

A case of primary Sjögren\u27s syndrome complicated with inflammatory myopathy and interstitial lung disease.

We experienced a case of a 63-year-old woman with primary Sjögren\u27s syndrome (pSS) complicated with inflammatory myopathy and interstitial lung disease (ILD). She had suffered from morning stiffness and dry mouth for 1 year without being medically examined. A chest CT scan demonstrated ground glass opacity and a reticular shadow in the lower lung field. A diagnosis of SS was made based on positive findings from Schirmer\u27s test, sialography of the parotid gland, a labial salivary gland biopsy and the presence of anti-SS-A antibody. Musculoskeletal symptoms were absent; however, the elevation of creatine kinase (CK) as well as magnetic resonance imaging (MRI)-proven inflammatory change of bilateral muscles of the thigh was evident. Histological examination of the thigh revealed diameter variation, degeneration of muscle fibers and inflammatory cell infiltration in the perivascular area, corresponding to the inflammatory myopathy of pSS. Oral prednisolone 30 mg/day was introduced, and serum CK rapidly decreased within 2 weeks. ILD also responded well to prednisolone without relapse. These clinical outcomes are consistent with extraglandular organ involvement of pSS.The original publication is available at www.springerlink.co

Sweet\u27s Syndrome Complicated by Kikuchi\u27s Disease and Hemophagocytic Syndrome which Presented with Retinoic Acid-inducible Gene-I in both the Skin Epidermal Basal Layer and the Cervical Lymph Nodes

A 21-year-old man was admitted to our hospital with a fever, erythema, cervical lymphadenopathy and pancytopenia. A diagnosis of Sweet\u27s syndrome (SS) with Kikuchi\u27s disease (KD) and hemophagocytic syndrome (HPS) was made based on the results of a bone marrow aspiration along with the results from biopsy specimens of the brachial skin and a cervical lymph node. The expression of retinoic acid-inducible gene-I (RIG-I) in the skin epidermal basal layer as well as in a cervical lymph node was revealed through immunohistochemistry. He successfully entered remission through treatment with prednisolone. This findings of this case indicate that when SS with KD presents as HPS, it may suggest an association with an RIG-I-related innate immunity

Comparative risk of hospitalized infection between biological agents in rheumatoid arthritis patients: A multicenter retrospective cohort study in Japan.

OBJECTIVE:Knowing the risk of hospitalized infection associated with individual biological agents is an important factor in selecting the best treatment option for patients with rheumatoid arthritis (RA). This study examined the comparative risk of hospitalized infection between biological agents in a routine care setting. METHODS:We used data for all RA patients who had first begun biological therapy at rheumatology divisions of participating community hospitals in Japan between January 2009 and December 2014. New treatment episodes with etanercept, infliximab, adalimumab, abatacept, or tocilizumab were included. Patients were allowed to contribute multiple treatment episodes with different biological agents. Incidence rates (IRs) of hospitalized infection during the first year of follow-up were examined. Cox regression analysis was used to calculate hazard ratios (HRs) for overall hospitalized infection and for pulmonary hospitalized infection, adjusting for possible confounders. RESULTS:A total of 1596 new treatment episodes were identified. The incidence of overall hospitalized infection during the first year was 86 with 1239 person-years (PYs), yielding a crude IR of 6.9 per 100 PYs (95% confidence interval [CI], 5.6-8.6). After correction for confounders, no significant difference in risk of hospitalized infection was observed between treatment groups: adjusted HRs (95% CI) were 1.54 (0.78-3.04) for infliximab, 1.72 (0.88-3.34) for adalimumab, 1.11 (0.55-2.21) for abatacept, and 1.02 (0.55-1.87) for tocilizumab compared with etanercept. Patient-specific factors such as age, RA functional class, body mass index (BMI), prednisolone use, and chronic lung disease contributed more to the risk of hospitalized infection than specific biological agents. The incidence of pulmonary hospitalized infection was 50 and a crude IR of 4.0 per 100 PYs (95% CI, 3.1-5.3). After adjustment for confounders, adalimumab had a significantly higher HR for pulmonary hospitalized infection compared with tocilizumab: an adjusted HR (95% CI) was 4.43 (1.72-11.37) for adalimumab. BMI, prednisolone use, diabetes mellitus, and chronic lung disease were also significant factors associated with the risk of pulmonary hospitalized infection. CONCLUSIONS:The magnitude of the risk of overall hospitalized infection was not determined by the type of biological agents, and patient-specific risk factors had more impact on the risk of hospitalized infection. For pulmonary hospitalized infections, the use of adalimumab was significantly associated with a greater risk of this complication than tocilizumab use