RETRACTED: Evidence for a functional role of IgE anticitrullinated protein antibodies in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease involving inflammation of the joints. Among the autoantibodies described in RA, anticitrullinated protein antibodies (ACPAs) are highly specific and predictive for RA. In addition, ACPAs have been implicated in the pathogenesis of RA. However, a direct functional response of immune cells from ACPA + RA patients toward citrullinated proteins has not been demonstrated. In this study, we show that exposure to citrullinated antigens leads to activation of basophils from ACPA + RA patients within 20 minutes. This was not observed after exposure of basophils to noncitrullinated control antigens or after stimulation of basophils from ACPA − RA patients and healthy controls. Basophil activation was correlated with the binding of citrullinated proteins to basophils. Furthermore, serum from ACPA + RA patients in contrast to that from ACPA − RA patients could specifically sensitize human FcεRI expressing rat basophil cells (RBL), enabling activation by citrullinated proteins. Mast cell degranulation products such as histamine levels were enhanced in synovial fluid of ACPA + RA patients as compared with ACPA − RA and osteoarthritis patients. In addition, histamine levels in synovial fluid from ACPA + RA patients correlated with IgE levels, suggesting degranulation of mast cells by cross-linking IgE. Immunohistochemistry on synovial biopsies demonstrated an increased number of degranulated CD117 + mast cells in ACPA + RA patients; IgE and FcεRI expression in synovial mast cells from ACPA + RA patients was increased. In conclusion, our results show an immunological response of immune cells from ACPA + RA patients in a citrulline-specific manner. Moreover, these data indicate a role for IgE-ACPAs and FcεRI-positive cells in the pathogenesis of RA.

Novel Phosphoinositide 3-Kinaseδ,γInhibitor: Potent Anti-Inflammatory Effects and Joint Protection in Models of Rheumatoid Arthritis

“…Oral treatment with another PI3Kd inhibitor, IC87114 (Sadhu et al, 2003), demonstrated a similar effect, implicating the d isoform activity rather than g in our studies (Zhang et al, 2008). Although the role of IgE in RA is not well defined, the presence of IgE anticitrullinated protein antibodies in RA patients supports a possible relationship of IgE and RA (Schuerwegh et al, 2010). Interestingly, phase I studies in humans have not shown an increase in IgE levels and suggest that this might be a rodent-specific phenomenon (Infinity Pharmaceuticals, unpublished observations).…”

Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage

“…This finding has made considerable impact, as it has opened up the way to relevant and novel insights into RA-diagnosis and etiopathology (1). For example, ACPA are now part of the new American College of Rheumatology/ European League Against Rheumatism criteria for RA (18), and have been implicated in RA-pathogenesis, both in animal models (19)(20)(21) and in ex vivo human studies (22)(23)(24)(25). Importantly, the description of ACPA has led to the realization that RA constitutes at least two clinical syndromes that share many clinical features, but differ with respect to genetic background, predisposing environmental factors and clinical progression/remission (3,4,(26)(27)(28).…”

Anti-citrullinated protein antibodies (ACPA) in early rheumatoid arthritis

“…ACPA have all immunoglobulin isotypes including IgM [40] and IgE ACPA [41]. IgM-CCP is present in early samples from both patients with UA and patients with RA, as well as in long-term follow-up samples from patients with RA [40].…”