Granulocyte autoantibodies are the main cause of autoimmune neutropenia (AIN).¹ Autoantibodies to the neutrophil-specific antigens of the NA system (isoform of neutrophil Fc receptor, also known as CD16) are associated with AIN.² In a pediatric population with AIN, neutrophil autoantibodies were detected in 119 of 121 patients; 10% of these autoantibodies had specificity for NA1 or NA2.³ 73% of infants presenting with autoimmune neutropenia and positive for NA1 autoantibodies expressed the HLA-DR2 antigen. All DR2-negative patients were DRw6.⁴ The frequency of granulocyte autoantibodies in SLE is reportedly about 50%.¹ Granulocyte autoantibodies are also found in fibrile non-hemolytic transfusion reactions, transfusion-associated acute lung injury and alloimmune neonatal neutropenia (ANN).⁵ Secondary AIN, the neutropenias of autoimmune disorders (SLE, Graves disease, drug-induced, Felty syndrome) share the antigen specificity to some extent.^1,6  A recent study assesses the role of granulocyte colony-stimulating factor (G-CSF) in AIN to conclude that G-CSF production in AIN is not increased despite the low neutrophil count, similar to thrombopoietin in immune thrombocytopenic purpura.⁷

Laboratory diagnosis of AIN is largely based on direct detection of granulocyte autoantibodies on the neutrophil surface by immunofluorescence (GIFT), EIA, RIA, flow cytometry (FC) or indirectly by detection of autoantibody effects (agglutination, cytotoxicity, opsonization). The direct assays are more specific and sensitive for AIN. Direct detection of granulocyte autoantibodies is usually difficult due to the low number and high tendency of granulocytes to aggregate in vitro. Currently, the method of choice for detection and quantitation of granulocytes autoantibodies of any isotype is by FC.¹ Of AIN patients, 30% are positive for granulocyte autoantibodies by FC compared to 15% by GIFT.^8,9 The isotype frequency of granulocyte autoantibodies is predominantly IgG alone (79%), but IgM (12%), IgG and IgM (21%) also occur. No data are available on IgA granulocyte autoantibodies.⁹

Beta-lactam antibiotics possibly trigger production of granulocyte autoantibody with resultant autoimmune neutropenia.¹⁰ New laboratory advancements and accumulation of data on granylocytes' antigens and antibodies has recently enabled the recommendation of guidelines for the laboratory investigation of autoimmune neutropenia.¹¹