Novel multiplex technology for diagnostic characterization of rheumatoid arthritis

Abstract Introduction The aim of this study was to develop a clinical-grade, automated, multiplex system for the differential diagnosis and molecular stratification of rheumatoid arthritis (RA). Methods We profiled autoantibodies, cytokines, and bone-turnover products in sera from 120 patients with a diagnosis of RA of < 6 months' duration, as well as in sera from 27 patients with ankylosing spondylitis, 28 patients with psoriatic arthritis, and 25 healthy individuals. We used a commercial bead assay to measure cytokine levels and developed an array assay based on novel multiplex technology (Immunological Multi-Parameter Chip Technology) to evaluate autoantibody reactivities and bone-turnover markers. Data were analyzed by Significance Analysis of Microarrays and hierarchical clustering software. Results We developed a highly reproducible, automated, multiplex biomarker assay that can reliably distinguish between RA patients and healthy individuals or patients with other inflammatory arthritides. Identification of distinct biomarker signatures enabled molecular stratification of early-stage RA into clinically relevant subtypes. In this initial study, multiplex measurement of a subset of the differentiating biomarkers provided high sensitivity and specificity in the diagnostic discrimination of RA: Use of 3 biomarkers yielded a sensitivity of 84.2% and a specificity of 93.8%, and use of 4 biomarkers a sensitivity of 59.2% and a specificity of 96.3%. Conclusions The multiplex biomarker assay described herein has the potential to diagnose RA with greater sensitivity and specificity than do current clinical tests. Its ability to stratify RA patients in an automated and reproducible manner paves the way for the development of assays that can guide RA therapy.http://deepblue.lib.umich.edu/bitstream/2027.42/116025/1/13075_2010_Article_3144.pd

The ink sac clouds octopod evolutionary history

Difficulties in elucidating the evolutionary history of the octopods have arisen from problems in identifying informative morphological characters. Recent classifications have divided the largest group, the incirrate octopods, into five groups. These include the pelagic superfamily Argonautoidea and three gelatinous pelagic families (Vitreledonellidae, Bolitaenidae, Amphitretidae). All benthic incirrate octopods have been accommodated in the family Octopodidae, itself divided into four subfamilies, Octopodinae, Eledoninae, Bathypolypodinae and Graneledoninae, which are defined by the presence or absence of an ink sac, and uniserial or biserial sucker arrangements on the arms. We used relaxed clock models in a Bayesian framework and maximum likelihood methods to analyse three nuclear and four mitochondrial genes of representatives from each of the previous subfamilies. Strong evidence indicates that the family Octopodidae is paraphyletic and contains the gelatinous pelagic families. The subfamilies of Octopodidae recognised in earlier works do not reflect evolutionary history. The following clades were supported in all analyses: (1) Eledone/Aphrodoctopus, (2) Callistoctopus/Grimpella/Macroctopus/Scaeurgus, (3) Abdopus/Ameloctopus/Amphioctopus/Cistopus/Hapalochlaena/Octopus, (4) Enteroctopus/Muusoctopus/Vulcanoctopus, (5) Vitreledonella/Japetella, (6) Southern Ocean endemic and deep-sea taxa with uniserial suckers. These clades form the basis for a suite of taxa assigned family taxonomic rank: Amphitretidae, Bathypolypodidae, Eledonidae, Enteroctopodidae, Megaleledonidae and Octopodidae sensu nov. They are placed within the superfamily Octopodoidea