Targeting of anti-citrullinated protein/peptide antibodies in rheumatoid arthritis using peptides mimicking endogenously citrullinated fibrinogen antigens

IntroductionWe have previously identified endogenously citrullinated peptides derived from fibrinogen in rheumatoid arthritis (RA) synovial tissues. In this study, we have investigated the auto-antigenicity of four of those citrullinated peptides, and explored their feasibility to target anti-citrullinated protein/peptide antibodies (ACPA).MethodsThe autoantigenic potential of the fibrinogen peptides was investigated by screening 927 serum samples from the Epidemiological Investigation of RA (EIRA) cohort on a peptide microarray based on the ImmunoCAP ISAC® system. In order to assay for ACPA blocking, two independent pools of purified ACPA were incubated with the respective targeting peptide prior to binding to cyclic citrullinated peptide (CCP)2 using the CCPlus® ELISA kit.ResultsTwo peptides derived from the fibrinogen α chain, Arg573Cit (563-583) and Arg591Cit (580-600), referred to as Cit573 and Cit591, and two peptides from the fibrinogen β chain, Arg72Cit (62-81) and Arg74Cit (62-81) (Cit72 and Cit74), displayed 65 %, 15 %, 35 %, and 53 % of immune reactivity among CCP2-positive RA sera, respectively. In CCP2-negative RA sera, a positive reactivity was detected in 5 % (Cit573), 6 % (Cit591), 8 % (Cit72), and 4 % (Cit74). In the competition assay, Cit573 and Cit591 peptides reduced ACPA binding to CCP2 by a maximum of 84 % and 63 % respectively. An additive effect was observed when these peptides were combined. In contrast, Cit74 and Cit72 were less effective. Cyclization of the peptide structure containing Cit573 significantly increased the blocking efficiency.ConclusionsHere we demonstrate extensive autoantibody reactivity against in vivo citrullinated fibrinogen epitopes, and further show the potential use of these peptides for antagonizing ACPA.     

Systematics and cladistics of Megalostomis Chevrolat,and the biogeography of Clytrini (Coleoptera: Cryptocephalinae)

We present a cladistic analysis of the subtribe Megalostomina, a Neotropical group of ‘case‐bearer’ leaf beetles. A comparative study of the external and internal adult morphology of Clytrini was undertaken. New characters are described for the subtribe Megalostomina, from the internal sac of aedeagus, which provide a useful phylogenetic signal. More than 180 photographs illustrating the most important characters (74 characters and their respective states) used in the cladistic analysis are provided. The cladistic analysis of 57 terminal taxa and 95 characters was undertaken, under equal weights, and also using implied weights as a means to down‐weight homoplasious characters. We test the monophyly and explore intergeneric relationships of the subtribe Megalostomina, and reconstruct the relationships among the species of Megalostomis Chevrolat. The 42 species recognized can be assigned either to a group mostly containing species of North and Central America, or to a larger one of mostly South American species. Support is low, and the formal naming of groups is deferred pending a revision of all Megalostomina. We confirm the subgenera of Megalostomis of previous classifications are unnatural, and the following changes in the generic classification of the subtribe Megalostomina are proposed: Coleorozena Moldenke syn.n. of Coscinoptera Lacordaire; Coleothorpa Moldenke syn.n. of Coscinoptera Lacordaire; and Euryscopa (Coleoguerina) Moldenke syn.n. of Coscinoptera Lacordaire. Furthermore, six formerly recognized subgenera of Megalostomis are considered junior synonyms of Megalostomis Chevrolat: Megalostomis (Minturnia) Lacordaire syn.n. ; Megalostomis (Heterostomis) Lacordaire syn.n. ; Megalostomis (Scaphigenia) Lacordaire syn.n. ; Megalostomis (Snellingia) Moldenke syn.n. ; Megalostomis (Coleobyersa) Moldenke syn.n. ; and Megalostomis (Pygidiocarina) Moldenke syn.n. Thus, no subgenera are recognized within Megalostomis. Previous hypotheses on Clytrini biogeography were revisited in the light of new biogeographic and phylogenetic knowledge. We hypothesize an origin of Clytrini in tropical/subtropical Gondwana, when South America, Africa, Madagascar and India were connected. Changes in the configuration of the tectonic plates in the Cenozoic allowed the dispersal of Clytrina to the Palaearctic and Nearctic regions, and dispersion of Babiina and Megalostomina through the Nearctic region.     

Resin gathering in neotropical resin bugs (Insecta: Hemiptera: Reduviidae): Functional and comparative morphology

Apiomerini (Reduviidae: Harpactorinae) collect plant resins with their forelegs and use these sticky substances for prey capture or maternal care. These behaviors have not been described in detail and morphological structures involved in resin gathering, transfer, and storage remain virtually undocumented. We here describe these behaviors in Apiomerus flaviventris and document the involved structures. To place them in a comparative context, we describe and document leg and abdominal structures in 14 additional species of Apiomerini that represent all but one of the 12 recent genera in the tribe. Based on these morphological data in combination with the behavioral observations on A. flaviventris, we infer behavioral and functional hypotheses for the remaining genera within the tribe Apiomerini. Setal abdominal patches for resin storage are associated with maternal care so far only documented for species of Apiomerus. Based on the occurrence of these patches in several other genera, we propose that maternal care is widespread within the tribe. Ventral abdominal glands are widespread within female Apiomerini. We propose that their products may prevent hardening of stored resins thus providing long‐term supply for egg coating. Judging from the diverse setal types and arrangements on the front legs, we predict six different behavioral patterns of resin gathering within the tribe. J. Morphol., 2011. © 2010 Wiley‐Liss, Inc.     

A Dated Phylogeny Complements Macroecological Analysis to Explain the Diversity Patterns in Geonoma (Arecaceae)

Integrating phylogenetic data into macroecological studies of biodiversity patterns may complement the information provided by present‐day spatial patterns. In the present study, we used range map data for all Geonoma (Arecaceae) species to assess whether Geonoma species composition forms spatially coherent floristic clusters. We then evaluated the extent to which the spatial variation in species composition reflects present‐day environmental variation vs. nonenvironmental spatial effects, as expected if the pattern reflects historical biogeography. We also examined the degree of geographic structure in the Geonoma phylogeny. Finally, we used a dated phylogeny to assess whether species richness within the floristic clusters was constrained by a specific historical biogeographic driver, namely time‐for‐diversification. A cluster analysis identified six spatially coherent floristic clusters, four of which were used to reveal a significant geographic phylogenetic structure. Variation partitioning analysis showed that 56 percent of the variation in species composition could be explained by spatial variables alone, consistent with historical factors having played a major role in generating the Geonoma diversity pattern. To test for a time‐for‐diversification effect, we correlated four different species richness measures with the diversification time of the earliest large lineage that is characteristic of each cluster. In support of this hypothesis, we found that geographic areas with higher richness contained older radiations. We conclude that current geographic diversity patterns in Geonoma reflect the present‐day climate, but to a larger extent are related to nonenvironmental spatial constraints linked to colonization time, dispersal limitation, and geological history, followed by within‐area evolutionary diversification. Abstract in Spanish is available at http://www.blackwell‐synergy.com/loi/btp .