Influence of peptidylarginine deiminase type 4 genotype and shared epitope on clinical characteristics and autoantibody profile of rheumatoid arthritis.

Background: Recent evidence suggests that distinction of subsets of rheumatoid arthritis (RA) depending on anticyclic citrullinated peptide antibody (anti-CCP) status may be helpful in distinguishing distinct aetiopathologies and in predicting the course of disease. HLA-DRB1 shared epitope (SE) and peptidylarginine deiminase type 4 (PADI4) genotype, both of which have been implicated in anti-CCP generation, are assumed to be associated with RA. Objectives: To elucidate whether PADI4 affects the clinical characteristics of RA, and whether it would modulate the effect of anti-CCPs on clinical course. The combined effect of SE and PADI4 on autoantibody profile was also analysed. Methods: 373 patients with RA were studied. SE, padi4_94C.T, rheumatoid factor, anti-CCPs and antinuclear antibodies (ANAs) were determined. Disease severity was characterised by cumulative therapy intensity classified into ordinal categories (CTI-1 to CTI-3) and by Steinbrocker score. Results: CTI was significantly associated with disease duration, erosive disease, disease activity score (DAS) 28 and anti-CCPs. The association of anti-CCPs with CTI was considerably influenced by padi4_94C.T genotype (C/C: ORadj=0.93, padj=0.92; C/T: ORadj=2.92, padj=0.093; T/T: ORadj=15.3, padj=0.002). Carriage of padi4_94T exhibited a significant trend towards higher Steinbrocker scores in univariate and multivariate analyses. An association of padi4_94C.T with ANAs was observed, with noteworthy differences depending on SE status (SE2: ORadj=6.20, padj,0.04; SE+: ORadj=0.36, padj=0.02) and significant heterogeneity between the two SE strata (p=0.006). Conclusions: PADI4 genotype in combination with anti- CCPs and SE modulates clinical and serological characteristics of RA

Identification and characterization of leucosis/sarcoma group of viruses. II. Activation and assay of L-R cells

Las células L-R descriptas en este trabajo, se obtuvieron por la inoculación de RSV parcialmente defectivo en cultivos de fibroblastos de embrión de pollo C/O. Bajo las condiciones empleadas en este sistema de test no se obtuvo la misma respuesta a los tres diferentes sub grupos virales del grupo Leucosis/Sarcoma que fueron testados. Queda por determinar si esta diferencia, es debida a las características de las cepas virales empleadas, a las células en que se realizó el ensayo o es una característica de los clones empleados en esta experiencia. De acuerdo a los resultados obtenidos no hay ningún tipo de interferencia a falla en la sensibilidad en el test empleado, por la producción de RSV (O) si es que se produce. La reproductibilidad de los resultados, la facilidad con que se realiza el test, el corto periodo de tiempo empleado, comparado con otros métodos y la simpleza del test, hacen de esta metodología un instrumento con grandes posibilidades de aplicación en la práctica del laboratorio de diagnósticoThe L-R cells described here were originated from CIO chick embryo fibroblast and the virus produced alter their activation was assayed in C/O fibroblasts. The fibroblast came from RIF free SPF flock. Under the conditions described here, the clones of L-R cells isolated did not show similar susceptibility to the different virus subgroup tested. Where this phenomenon was due to the susceptibility of the clones, the assay cells system used, or the strain of virus tested, was not determined. The results obtained with samples from field conditions and experimentally inoculated birds, showed that in this procedure the system of testing the RSV (O) production by the L-R cells (if any), did not interfere in the system, nor with the sensitivity of the testFacultad de Ciencias Veterinaria

Identification and characterization of leucosis/sarcoma group of viruses. II. Activation and assay of L-R cells

Las células L-R descriptas en este trabajo, se obtuvieron por la inoculación de RSV parcialmente defectivo en cultivos de fibroblastos de embrión de pollo C/O. Bajo las condiciones empleadas en este sistema de test no se obtuvo la misma respuesta a los tres diferentes sub grupos virales del grupo Leucosis/Sarcoma que fueron testados. Queda por determinar si esta diferencia, es debida a las características de las cepas virales empleadas, a las células en que se realizó el ensayo o es una característica de los clones empleados en esta experiencia. De acuerdo a los resultados obtenidos no hay ningún tipo de interferencia a falla en la sensibilidad en el test empleado, por la producción de RSV (O) si es que se produce. La reproductibilidad de los resultados, la facilidad con que se realiza el test, el corto periodo de tiempo empleado, comparado con otros métodos y la simpleza del test, hacen de esta metodología un instrumento con grandes posibilidades de aplicación en la práctica del laboratorio de diagnósticoThe L-R cells described here were originated from CIO chick embryo fibroblast and the virus produced alter their activation was assayed in C/O fibroblasts. The fibroblast came from RIF free SPF flock. Under the conditions described here, the clones of L-R cells isolated did not show similar susceptibility to the different virus subgroup tested. Where this phenomenon was due to the susceptibility of the clones, the assay cells system used, or the strain of virus tested, was not determined. The results obtained with samples from field conditions and experimentally inoculated birds, showed that in this procedure the system of testing the RSV (O) production by the L-R cells (if any), did not interfere in the system, nor with the sensitivity of the testFacultad de Ciencias Veterinaria

Phase 1b randomized, double-blind study of namilumab, an anti-granulocyte macrophage colony-stimulating factor monoclonal antibody, in mild-to-moderate rheumatoid arthritis

Change from baseline in swollen (a) and tender (b) joint counts. *Error bars show upper SE for placebo and lower SE for namilumab. SE standard error, SJC swollen joint count, TJC tender joint count. (PDF 1292 kb

Crowd Verifiable Zero-Knowledge and End-to-end Verifiable Multiparty Computation

Auditing a secure multiparty computation (MPC) protocol entails the validation of the protocol transcript by a third party that is otherwise untrusted. In this work, we introduce the concept of end-to-end verifiable MPC (VMPC), that requires the validation to provide a correctness guarantee even in the setting that all servers, trusted setup primitives and all the client systems utilized by the input-providing users of the MPC protocol are subverted by an adversary. To instantiate VMPC, we introduce a new concept in the setting of zero-knowlegde protocols that we term crowd verifiable zero-knowledge (CVZK). A CVZK protocol enables a prover to convince a set of verifiers about a certain statement, even though each one individually contributes a small amount of entropy for verification and some of them are adversarially controlled. Given CVZK, we present a VMPC protocol that is based on discrete-logarithm related assumptions. At the high level of adversity that VMPC is meant to withstand, it is infeasible to ensure perfect correctness, thus we investigate the classes of functions and verifiability relations that are feasible in our framework, and present a number of possible applications the underlying functions of which can be implemented via VMPC

Long-term efficiency of infliximab in patients with ankylosing spondylitis : real life data confirm the potential for dose reduction

Objective: To analyse the treatment outcome of patients with ankylosing spondylitis (AS) in the European AS infliximab cohort (EASIC) study after a total period of 8 years with specific focus on dosage and the duration of intervals between infliximab infusions. Methods: EASIC included patients with AS who had received infliximab for 2 years as part of the ASSERT trial. After that period, rheumatologists were free to change the dose or the intervals of infliximab. Clinical data were status at baseline, end of ASSERT and for a total of 8 years of follow-up. Results: Of the initially 71 patients with AS from EASIC, 55 patients (77.5%) had completed the 8th year of anti-tumour necrosis factor (TNF) treatment. Of those, 48 patients (87.3%) still continued on infliximab. The mean infusion interval increased slightly from 6 to 7.1 +/- 1.5 weeks, while 45.8% patients had increased the intervals up to a maximum of 12 weeks. The mean infliximab dose remained stable over time, with a minimum of 3.1 mg/kg and a maximum of 6.4 mg/kg. In patients receiving <5 mg/kg infliximab, the mean infusion interval increased to 7.0 +/- 1.2 weeks. In total, the mean cumulative dose per patient and per year decreased from 3566.30 to 2973.60 mg. Conclusions: We could observe that over a follow-up of 8 years of treatment with infliximab, >85% patients still remained on the same treatment, without any major safety events. Furthermore, both the infusion intervals and also the mean infliximab dose were modestly reduced in >= 70% of the patients without the loss of clinical efficiency