lewis-x-antigen and Giant-Cell-Arteritis

Giant cell arteritis (GCA) is a common form of primary systemic vasculitis in adults, with no reliable indicators of prognosis or treatment responses. We used single cell technologies to comprehensively map immune cell populations in the blood of patients with GCA and identified the CD66b+CD15+CD10lo/-CD64- band neutrophils and CD66bhiCD15+CD10lo/-CD64+/bright myelocytes/metamyelocytes to be unequivocally associated with both the clinical phenotype and response to treatment. Immature neutrophils were resistant to apoptosis, remained in the vasculature for a prolonged period of time, interacted with platelets, and extravasated into the tissue surrounding the temporal arteries of patients with GCA. We discovered that immature neutrophils generated high levels of extracellular reactive oxygen species, leading to enhanced protein oxidation and permeability of endothelial barrier in an in vitro coculture system. The same populations were also detected in other systemic vasculitides. These findings link functions of immature neutrophils to disease pathogenesis, establishing a clinical cellular signature of GCA and suggesting different therapeutic approaches in systemic vascular inflammation.

Topics: Aged; Antigens, CD; Antigens, Surface; Apoptosis; Autoimmune Diseases; Cell Adhesion Molecules; Cell Line; Cell Lineage; Coculture Techniques; Female; Giant Cell Arteritis; GPI-Linked Proteins; Granulocyte Precursor Cells; Humans; Leukocyte Count; Lewis X Antigen; Male; Middle Aged; Neprilysin; Neutrophils; Oxidation-Reduction; Prognosis; Reactive Oxygen Species; Single-Cell Analysis; Systemic Vasculitis; Temporal Arteries; Vascular Diseases

To determine the frequency of skip lesions in an unselected series of temporal artery biopsies and compare the results with other series.. The study was a retrospective review of 102 consecutive temporal artery biopsies taken in a five year period (1992-1997) in one large hospital.. 35 cases (34.3%) showed evidence of active cranial vasculitis with pathological evidence of inflammation of the intima or media, with or without giant cells. Three of these cases (8.5%) showed apparent skip lesions: normal intima, media, and adventitia in one segment while in other segments there was clear evidence of active vasculitis. Immunocytochemical stains for leucocyte common antigen (LCA) and CD15 were helpful in identifying the absence of intimal or medial inflammatory cell infiltrates within skip lesions. Skip lesions have been described in up to 28.3% of cases in some series, while others have not found evidence of skip lesions or have identified them in a much smaller percentage of cases.. In this series skip lesions were relatively rare, accounting for 8.5% of cases of active vasculitis. The degree of inflammation in temporal arteritis is discontinuous. Immunostaining for inflammatory cells, for example LCA and CD15, may be helpful in identifying the presence of an inflammatory cell infiltrate in skip lesion segments of the temporal artery.

Topics: Biopsy; Giant Cell Arteritis; Humans; Immunoenzyme Techniques; Leukocyte Common Antigens; Lewis X Antigen; Retrospective Studies; Temporal Arteries; Tunica Intima; Tunica Media