Trial design We present a study protocol for a multi-centre, randomised, double-blind, parallel-group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class co-stimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants who were at least 18 years old, who reported inflammatory sounding joint pain (clinically suspicious arthralgia) and who were found to be positive for serum autoantibodies associated with rheumatoid arthritis (RA) were eligible for enrolment. All study subjects were randomly assigned to receive weekly injections of investigational medicinal product, either abatacept or placebo treatment over the course of a 52-week period. Participants were followed up for a further 52 weeks. The primary endpoint was defined as the time to development of at least three swollen joints or to the fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other’s assessments for the duration of the study. Conclusions There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment and the challenges associated with defining the “at risk” state and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration Current Controlled Trials, ID: ISRCTN46017566 . Registered on 4 July 2014. Electronic supplementary material The online version of this article (10.1186/s13063-019-3403-7) contains supplementary material, which is available to authorized users.

Trial design: We present a study protocol for a multi-centre, randomised, double blind, parallel group, placebo-controlled trial that seeks to test the feasibility, acceptability and effectiveness of a 52-week period of treatment with the first-in-class costimulatory blocker abatacept for preventing or delaying the onset of inflammatory arthritis. Methods: The study aimed to recruit 206 male or female subjects from the secondary care hospital setting across the UK and the Netherlands. Participants aged 18 or over who report inflammatory sounding joint pain (clinically suspicious arthralgia) and who are found to be positive for serum autoantibodies associated with RA were eligible for enrolment. All study subjects were randomised to receive weekly injections of investigational medicinal product (IMP), either abatacept or placebo treatment over a 52-week period. Participants were then followed up for a further 52 weeks. The primary endpoint was defined as the time to development of ≥ 3 swollen joints, or to the fulfilment of the 2010 ACR/EULAR classification criteria for RA using swollen but not tender joints, whichever endpoint was met first. In either case, swollen joints were confirmed by ultrasonography. Participants, care givers, and those assessing the outcomes were all blinded to group assignment. Clinical assessors and ultrasonographers were also blinded to each other’s assessments for the duration of the study. Conclusions: There is limited experience of the design and implementation of trials for the prevention of inflammatory joint diseases. We discuss the rationale behind choice and duration of treatment, the challenges associated with defining the “at risk” state, and offer pragmatic solutions in the protocol to enrolling subjects at risk of RA. Trial registration: Current Controlled Trials, ID: ISRCTN46017566. Registered on 04 July 2014.

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Alveolar macrophages and mast cells isolated from guinea pig lung were passively sensitized with IgG1, IgG2, or serum obtained from guinea pigs actively sensitized with ovalbumin. The release of histamine by mast cells and of thromboxane A2 by alveolar macrophages upon ovalbumin challenge indicated that both antibodies and serum were capable of sensitizing these cells with similar effectiveness. Heating the serum at 56 degrees C for 4 h to inactivate IgE did not modify the antigen-dependent response of lung cells. These results suggest a predominant role for IgG in the allergic response of the guinea pig through the activation of different cell types such as lung mast cells and alveolar macrophages.