Anti-citrullinated protein antibodies cause arthritis by cross-reactivity to joint cartilage

Today, it is known that autoimmune diseases start a long time before clinical symptoms appear. Anti-citrullinated protein antibodies (ACPAs) appear many years before the clinical onset of rheumatoid arthritis (RA). However, it is still unclear if and how ACPAs are arthritogenic. To better understand the molecular basis of pathogenicity of ACPAs, we investigated autoantibodies reactive against the C1 epitope of collagen type II (CII) and its citrullinated variants. We found that these antibodies are commonly occurring in RA. A mAb (ACC1) against citrullinated C1 was found to cross-react with several noncitrullinated epitopes on native CII, causing proteoglycan depletion of cartilage and severe arthritis in mice. Structural studies by X-ray crystallography showed that such recognition is governed by a shared structural motif "RG-TG" within all the epitopes, including electrostatic potential-controlled citrulline specificity. Overall, we have demonstrated a molecular mechanism that explains how ACPAs trigger arthritis

Reasoning from connectives and relations between entities

This article reports investigations of inferences that depend both on connectives between clauses, such as or else, and on relations between entities, such as in the same place as. Participants made more valid inferences from biconditionals—for instance, Ann is taller than Beth if and only if Beth is taller than Cath—than from exclusive disjunctions (Exp. 1). They made more valid transitive inferences from a biconditional when a categorical premise affirmed rather than denied one of its clauses, but they made more valid transitive inferences from an exclusive disjunction when a categorical premise denied rather than affirmed one of its clauses (Exp. 2). From exclusive disjunctions, such as Either Ann is not in the same place as Beth or else Beth is not in the same place as Cath, individuals tended to infer that all three individuals could be in different places, whereas in fact this was impossible (Exps. 3a and 3b). The theory of mental models predicts all of these results

Clinical and Non-Clinical Aspects of Distal Radioulnar Joint Instability

Untreated distal radioulnar joint (DRUJ) injuries can give rise to long lasting complaints. Although common, diagnosis and treatment of DRUJ injuries remains a challenge. The articulating anatomy of the distal radius and ulna, among others, enables an extensive range of forearm pronosupination movements. Stabilization of this joint is provided by both intrinsic and extrinsic stabilizers and the joint capsule. These structures transmit the load and prevent the DRUJ from luxation during movement. Several clinical tests have been suggested to determine static or dynamic DRUJ stability, but their predictive value is unclear. Radiologic evaluation of DRUJ instability begins with conventional radiographs in anterioposterior and true lateral view. If not conclusive, CT-scan seems to be the best additional modality to evaluate the osseous structures. MRI has proven to be more sensitive and specific for TFCC tears, potentially causing DRUJ instability. DRUJ instability may remain asymptomatic. Symptomatic DRUJ injuries treatment can be conservative or operative. Operative treatment should consist of restoration of osseous and ligamenteous anatomy. If not successful, salvage procedures can be performed to regain stability