Priority PaPer evaluation B lymphocytes may play a significant role in large-vessel vasculitis

Takayasu arteritis (TAK) is a chronic granulomatous vasculitis involving the aorta and its major branches. Due to the tropism of TAK for large arteries, tissue samples are not readily available. Vascular specimens are usually obtained at the time of bypass surgery or death from chronic complications and show predominantly fibrotic changes with various degrees of chronic inflammation. However, during earlier stages of the disease, that the vessel wall is infiltrated by lymphocytes and macrophages that undergo granulomatous differentiation with typical formation of multinucleated giant cells [1]. This pattern, characteristic of a delayed-type hypersensitivity reaction, suggests the predominant participation of Th1-mediated mechanisms in the pathogenesis of vascular inflammation in TAK. Immunopathology studies have shown that inflammatory infiltrates are mainly constituted by CD4 T cells and activated macrophages. Adaptive immune response against unknown antigens is thought to play a major role in the pathogenesis of TAK [2,3]. This concept is supported by several observations. Although some heterogeneity exists among studies performed in different geographic areas and ethnicities, genetic risk is associated with polymorphisms in the major histocompatibility complex (MHC) region [2]. Analysis of T-cell receptor Va-Vb gene usage shows that infiltrating lymphocytes are oligoclonal, suggesting an antigen-driven immune response [3]. Smooth muscle cells undergo apoptosis and this is thought to be driven by cytotoxic T cells [2,4]. There is evidence that g/d T lymphocytes and natural killer cells also contribute to cytotoxicity and several apoptosis-triggering molecules are upregulated in inflammatory infiltrates [4]. More recently, the potential participation of B cells in TAK has attracted some interest. B lymphocytes and plasma cells may be present in TAK lesions, particularly in the adventitia [1]. Antiendothelial cell antibodies can be detected in active patients. Some are addressed to annexin V and may promote endothelial cell apoptosis. The specificities of antiendothelial cell antibodies in patients with TAK appear to be heterogeneous [2]. Recently, antibodies recognizing a 62-kD protein in aortic endothelial cells have been detected in patients with TAK and are able to elicit endothelial cell proinflammatory responses and apoptosis [5]. Although endothelial injury does not seem to be the major pathogenic event in a large-vessel vasculitis,increased endothelial cell proinflammatoy activity may participate in the recruitment of inflammatory cells [6] and endothelial damage may contribute to endothelial dysfunction and premature atherosclerosis observed in TAK patients. Regardless of their precise role in vascular inflammation and injury, the presence of antiendothelial anti bodies, observed by several investigators, indicates autoreactive B-cell activation. Underlining the pathogenic potential of B cells, Hoyer et al. have recently reported abnormalities in circulating B-derived cell subsets in patients with TAK [7]. The authors not only found increased numbers of memory (CD19, CD20 and CD27) B cells and decreased numbers of naive (CD19, CD20 and CD27) Evaluation of: Hoyer BF, Mumtaz IM, Loddenkemper K et al. Takayasu arteritis is characterised by disturbances of B cell homeostasis and responds to B cell depletion therapy with rituximab. Ann. Rheum. Dis. 71, 75–79 (2012). The novel finding of increased number of circulating, newly differentiated, plasmablasts in Takayasu arteritis and their relationship to disease activity raises interesting questions about the role of B lymphocytes in large-vessel vasculitis. Whether this observation is relevant to the pathogenesis of vascular inflammation in Takayasu arteritis or is only a biomarker of immune activation needs to be investigated. Response of a few patients to B-cell depletion therapy supports an important role of B lymphocytes in vascular inflammation, but needs to be confirmed in clinical trials.