Autoimmune neutropenias: pathogenesis and diagnostic tests

Antineutrophil antibodies are well recognized causes of neutropenia, producing both quantitative and qualitative defects in neutrophils and increased risk for infection. In primary autoimmune neutropenia (AIN) of infancy, a moderate to severe neutropenia is the sole abnormality; it is rarely associated with serious infections and exhibits a self-limited course. Chronic idiopathic neutropenia of adults is characterized by occurrence in late childhood or adulthood, greater prevalence among females than among males, and rare spontaneous remission. Secondary AIN is more commonly seen in adults and underlying causes include collagen disorders, drugs, viruses and lymphoproliferative disorders. In most patients with AIN, antibodies recognize antigens located on the IgG Fc receptor type 3b but other target antigens have been recently identified in secondary AIN. Granulocyte colonystimulating factor is a proven treatment in patients with AIN of all types and is now preferred to other possible therapies. Introduction The term ‘neutropenia’ is used to define a condition in which circulating neutrophils number less than 1500/μl. Neutropenias can be classified according to the mechanism of induction, and so there are forms due to decreased production of neutrophils, to sequestering of neutrophils from endothelial or tissue pools, and to increased peripheral destruction of neutrophils. It is perhaps more useful for purposes of differential diagnosis to distinguish between congenital and acquired forms, the latter being subdivided according to their pathogenesis or aetiological agent (Table 1). Regardless of the cause, the clinical result of neutropenia is always an increased infective diathesis, with frequency and severity that are directly proportional to the degree of neutropenia. This is considered mild when the neutrophil count is between 1000 and 1500/μl, moderate when it is between 500 and 1000/μl, and severe when it is less than 500/μl. Other factors may influence the severity of the infective diathesis in a neutropenic patient: the speed of onset and the duration of the neutropenia, the bone marrow myeloid reserves, the absolute circulating monocyte count and the functional status of phagocytes. Immune mediated neutropenias (Table 1) involve a low neutrophil count resulting from increased peripheral destruction due to antibodies directed against the cell membrane antigens. The field of immune mediated neutropenias includes various conditions such as alloimmune neutropenias (caused by maternal–fetal incompatibility or transfusion reactions) and true autoimmune forms. This review focuses on the true autoimmune forms, which may be primary (i.e. not associated with other pathologies) or secondary (usually to autoimmune or haematological diseases). Autoimmune neutropenias: pathogenesis and diagnostic tests The first convincing evidence that antineutrophil autoantibodies could cause neutropenia was presented in 1975, when Boxer and coworkers [1] described five cases caused by antineutrophil antibodies that facilitated phagocytosis of opsonized neutrophils by splenic macrophages, and altered some functional features of neutrophils. In the same year, Lalezari and coworkers [2] showed that, to some extent, autoantibodies could cause chronic neutropenia. Earlier experiments conducted by Lawrence and coworkers [3] and Simpson and Ross [4] had already demonstrated the importance of antineutrophil autoantibodies in causing neutropenia; those investigators showed that infusion into guinea pigs of rabbit anti-guinea-pig neutrophil antibodies caused neutropenia, as a result of phagocytosis of opsonized neutrophils by splenic and bone marrow macrophages. In humans autoantibodies also play a major opsonizing role – possibly the main one – in inducing autoimmune neutropenia (AIN) [1,5]. Review Primary and secondary autoimmune neutropenia Franco Capsoni1, Piercarlo Sarzi-Puttini2 and Alberto Zanella3 1Rheumatology Unit, Istituto Ortopedico Galeazzi, University of Milan, Milan, Italy 2Rheumatology Unit, Ospedale L Sacco, University of Milan, Milan, Italy 3Hematology Unit, Ospedale Maggiore Policlinico, Fondazione IRCCS, University of Milan, Milan, Italy Corresponding author: Franco Capsoni, [email protected] Published: 31 August 2005 Arthritis Research & Therapy 2005, 7:208-214 (DOI 10.1186/ar1803) This article is online at http://arthritis-research.com/content/7/5/208 © 2005 BioMed Central Ltd