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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease more prevalent in people of African and Asian origin than Caucasian origin. FcgammaRIIb is an inhibitory Fc receptor with a critical role in immune regulation. Mouse data suggest that FcgammaRIIb deficiency increases susceptibility to autoimmune disease but protects against infection. We(More)
The response of a leukocyte to immune complexes (ICs) is modulated by receptors for the Fc region of IgG (FcgammaRs), and alterations in their affinity or function have been associated with risk of autoimmune diseases, including systemic lupus erythematosus (SLE). The low-affinity FcgammaR genomic locus is complex, containing regions of copy number(More)
The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the deposition of immune complexes in organs such as the kidney. This occurs as a result of multiple immunological abnormalities, including the production of high levels of autoantibody and dysregulated handling of immune complexes. Receptors for the Fc portion of IgG are(More)
Autoimmune diseases are common and debilitating, but their severe manifestations could be reduced if biomarkers were available to allow individual tailoring of potentially toxic immunosuppressive therapy. Gene expression-based biomarkers facilitating such tailoring of chemotherapy in cancer, but not autoimmunity, have been identified and translated into(More)
Polygenic autoimmune diseases, such as systemic lupus erythematosus (SLE), are a significant cause of morbidity and mortality worldwide. In recent years, functionally important genetic polymorphisms conferring susceptibility to SLE have been identified, but the evolutionary pressures driving their retention in the gene pool remain elusive. A defunctioning,(More)
Copy number (CN) variation (CNV) has been shown to be common in regions of the genome coding for immune-related genes, and thus impacts upon polygenic autoimmunity. Low CN of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcgammaRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on(More)
Low-affinity Fcgamma receptors (FcgammaRs) mediate the effects of immunoglobulin G (IgG) antibodies on leukocytes, including recruitment to inflammatory lesions, phagocytosis, antibody-dependent cellular cytotoxicity, release of inflammatory mediators and regulation of B cell activation. These functions are an important part of the mammalian response to(More)
The diagnosis of gut vasculitis infers a poor prognosis necessitating aggressive therapy. We describe a case with predominant features of a skin-limited vasculitis but atypical debilitating abdominal symptoms. Although endoscopic biopsies were unremarkable, full thickness biopsy taken at laparotomy revealed a necrotizing vasculitis. After treatment with(More)
BACKGROUND There is an increasing appreciation of the deleterious effects of antibody and B cells on acute and chronic transplant outcomes. Many effector functions of antibody are mediated by a family of receptors (FcγRs) that are expressed on most immune cells, including neutrophils, natural killer cells, and B cells. Most FcγRs are activating and(More)
The aetiology of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis has not been well defined. Here we review two factors which may play a role in the pathogenesis of the disease: genetics and infection. In particular, we discuss the role of autoantibodies to LAMP-2, which may arise following infection with Gram-negative bacteria,(More)