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Giant Cell Arteritis: Multiple Pathogenic Mechanisms and Potential Treatments
Author(s) -
FernándezFernández Francisco J.,
Pía Gonzalo,
Sesma Pascual
Publication year - 2014
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/head.12435
Subject(s) - fern , library science , medicine , bioinformatics , biology , computer science , botany
We read with interest the excellent article “Giant cell arteritis” by Smith and Swanson. The authors note several factors that have putative roles in the pathogenesis of giant cell arteritis (GCA). In this regard, we would like to mention an additional point. Recently, several cases of polymyalgia rheumatica/GCA occurring in patients who received ipilimumab were reported. Ipilimumab is an immunomodulating agent approved for the treatment of metastatic melanoma. This drug works by inhibiting cytotoxic T-lymphocyte antigen 4 (CTLA4) expressed on the surface of activated T cells and, by blocking CTLA4, ipilimumab disinhibits T cells and potentiates immune responses. As a result of the upregulation of the immune system, numerous immune-mediated adverse events have been reported including enterocolitis, dermatitis, hepatitis, hypophysitis, and polymyalgia rheumatica/GCA. Thus, there should be a lower threshold for suspecting polymyalgia rheumatica and GCA in patients with compatible symptoms, if they have previously been treated with ipilimumab. In this respect, ipilimumab appears to be unique because no other drug has clearly been implicated as an inciting trigger in the development of polymyalgia rheumatica/GCA. The publication of these cases is important because they represent a stimulus for the study of pathogenic mechanisms and potential treatments. It would be interesting to evaluate ipilimumab in experimental models and assess whether this immunomodulatory agent can induce GCA. This would allow an improved experimental model to better understand certain aspects of the pathogenesis and to test the effectiveness of different drugs. In this context, abatacept is included in the list of potential drugs. Abatacept is a fusion protein that consists of the extracellular domain of CTLA4 and the Fc portion of immunoglobulin G 1. CTLA4-Ig binds cluster of differentiation (CD)80 (B7-1) and CD86 (B7-2) on antigen presenting cells, thereby acting as a competitive inhibitor of the CD28-B7 costimulatory interaction, and it prevents the second activation signal received by T cells via CD28. Currently, a clinical trial on the effectiveness of this drug in treating GCA and Takayasu’s arteritis is underway (ClinicalTrials.gov Identifier: NCT00556439).