9 research outputs found
Divergent chemokine receptor expression and the consequence for human IgG4 B cell responses
IgG4 antibodies are unique to humans. IgG4 is associated with tolerance during immunotherapy in allergy, but also with pathology, as in pemphigus vulgaris and IgG4‐related disease. Its induction is largely restricted to non‐microbial antigens, and requires repeated or prolonged antigenic stimulation, for reasons poorly understood. An important aspect in generating high‐affinity IgG antibodies is chemokine receptor‐mediated migration of B cells into appropriate niches, such as germinal centers. Here, we show that compared to IgG1 B cells, circulating IgG4 B cells express lower levels of CXCR3, CXCR4, CXCR5, CCR6, and CXCR7, chemokine receptors involved in germinal center reactions and generation of long‐lived plasma cells. This phenotype was recapitulated by in vitro priming of naive B cells with an IgG4‐inducing combination of TFH/TH2 cytokines. Consistent with these observations, we found a low abundance of IgG4 B cells in secondary lymphoid tissues in vivo, and the IgG4 antibody response is substantially more short‐lived compared to other IgG subclasses in patient groups undergoing CD20+ B cell depletion therapy with rituximab. These results prompt the hypothesis that factors needed to form IgG4 B cells restrain at the same time the induction of a robust migratory phenotype that could support a long‐lived IgG4 antibody response
Experiences from experimental and numerical springback studies of a semi-industrial forming tool
Complement factor 5 blockade reduces porcine myocardial infarction size and improves immediate cardiac function
Extracellular Vesicle Proteins Associated with Systemic Vascular Events Correlate with Heart Failure: An Observational Study in a Dyspnoea Cohort
The complement system as a potential therapeutic target in rheumatic disease
Complement activation is associated with common rheumatic diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic vasculitis. Evidence linking complement activation to these diseases includes the presence of complement deposition in affected tissues, decreased levels of complement proteins and high levels of complement activation fragments in the blood and/or synovial fluid of patients with these diseases, as well as data from experimental models. Eculizumab, a monoclonal antibody that inhibits the complement component C5, is now approved for the treatment of rare conditions involving complement hyperactivation, and the success of this therapy has renewed interest in understanding the utility of complement inhibition in rheumatological practice, particularly for SLE. For example, inhibiting C5 is a potential means of reducing glomerular inflammation in lupus nephritis or treating thrombotic microangiopathy in SLE. The complement system is one of multiple mediators of tissue injury in complex diseases such as SLE, and identifying the disease context in which complement activation has a predominant role is a challenge. An added difficulty in RA is identifying a role for therapeutic complement inhibition within the diverse treatment modalities already available. In this Review, evidence for the therapeutic potential of complement manipulation in rheumatology practice is evaluated