Transcription profiling of CD14 monocytyes and CD16 neutrophils from patients with systemic lupus erythematosus

ABSTRACT: Copy number 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 copy number of FCGR3B has recently been associated with systemic lupus erythematosus (SLE). FcγRIIIb is a glycosylphosphatidylinositol-linked, low affinity receptor for IgG found predominantly on human neutrophils. We present novel data demonstrating that both in a family with FcγRIIIb-deficiency, and in the normal population, FCGR3B CNV correlates with protein expression, with neutrophil uptake of and adherence to immune complexes, and with soluble serum FcγRIIIb. Reduced FcγRIIIb expression is thus likely to contribute to the impaired clearance of immune complexes which is a feature of SLE, explaining the association between low FCGR3B CNV and SLE that we have confirmed in a Caucasian population. In contrast, anti-neutrophil cytoplasmic antibody -associated vasculitis (AASV), a disease not associated with immune complex deposition, is associated with high FCGR3B CN. Thus we define a role for FCGR3B CNV in immune complex clearance, a function which may explain why low FCGR3B CNV is associated with SLE but not AASV. This is the first report of an association between disease-related gene CNV and variation in protein expression and function that may contribute to autoimmune disease susceptibility.

ORGANISM(S): Homo sapiens

DISEASE(S): systemic lupus erythematosus

SUBMITTER: Paul Lyons 

PROVIDER: E-TABM-463 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress