Quarterly medical review
Autoimmune neutropenia

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Summary

Autoimmune neutropenia (AIN) is a rare entity caused by antibodies directed against neutrophil-specific antigens. It includes primary and secondary autoimmune neutropenia. Acute autoimmune neutropenia can be related to drug-induced mechanism or viral infections. Chronic autoimmune neutropenias occur in the context of autoimmune diseases, hematological malignancies, such as large granular lymphocyte leukemia, primary immune deficiency syndromes or solid tumors. The therapeutic management depends on the etiology. Granulocyte growth factor is the main therapeutic option, raising the question of their long-term utilization safety. Corticosteroids or immunosuppressive therapy are indicated in infection-related AIN or in case of symptomatic autoimmune disease or LGL leukemia.

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Pathogenesis of immune thrombocytopenia

Douglas B Cines, Adam Cuker, John W Semple

ITP and international guidelines, what do we know, what do we need?

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Thrombopietic agents: There is still much to learn

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Is B-cell depletion still a good strategy for treating immune thrombocytopenia?

Bertrand Godeau, Roberto Stasi

Novel treatments for immune thrombocytopenia

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Warm autoimmune hemolytic anemia: advances in pathophysiology and treatment

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Autoimmune neutropenia

Aline Moignet, Thierry Lamy

Section snippets

How PMN homeostasis is regulated?

In physiological situation, bone marrow produces about 109 PMN per kilo of body weight per day [2], [3]. Progenitors, precursors and marrow mature neutrophils represent 95% of PNN reserves [4]. Myeloid stem cells and progenitors will divide four or five times before beginning the maturation phase. During this maturation stage, the nucleus segments and the primary and secondary cytoplasmic granules appear. Primary granules contain bactericidal proteins (MPO, proteinase 3, elastase or cathepsin

Physiopathology of autoimmune neutropenias

The acquired autoimmune neutropenia are characterized by the presence of an antibody, usually of immunoglobulin G (IgG) directed against PMN specific antigens. These autoantibodies agglutinate neutrophils, which are then phagocytized. Those opsonized neutrophils are cleared from the circulation by the spleen and by various tissues containing phagocytic cells. There are also central mechanisms to immune neutropenia: lymphocytes from patients with Felty's syndrome or systemic lupus have been

Human neutrophil alloantigen and their methods of detection

Anti-neutrophil antibodies, called Human Neutrophil Alloantigen (HNA) antibodies are directed against neutrophil surface glycoproteins. The last nomenclature, written in 1998, is based on the glycoprotein location. HNA antibodies are responsible for several clinical conditions: autoimmune neutropenia but also transfusion-related acute lung injury (TRALI), febrile transfusion reactions, immune neutropenia after bone marrow transplantation and drug-induced immune neutropenia. Seven antigens have

Spectrum of AIN

Autoimmune neutropenia may display acute or chronic evolution. Every type of neutropenia discussed in this review comes under a combination of physiopathology mechanisms, including a variable part of autoimmunity. Acute neutropenia lasts by definition less than 3 months. It is mostly explained by drug-induced mechanisms in adulthood and by viral infections during childhood. Chronic neutropenia is rare but can be associated with various clinical conditions. It can be related to an acquired or a

Associated to infectious diseases

There are several studies [25], [26] reporting an infectious origin of AIN. Responsible infectious agents for neutropenia are mostly virus: human herpes virus-6 (HHV-6), enterovirus, influenza, parvoB19, EpsteinBarr virus (EBV), cytomegalovirus (CMV) with a variable frequency according to series. The large majority of these children was younger than 2 years and presented transient neutropenia (less than 2 months). These viral primo infections could be accompanied by a transient neutropenia. They

Primary autoimmune neutropenia

Primary autoimmune neutropenia is mainly diagnosed at the age of 5 to 15 months. Spontaneous remission occurred for nearly all the patients during the first or the second year following the neutropenia apparition. Autoantibodies are not easily detected and the screening had to be repeated several times. About 35% of the autoantibodies showed preferential binding to NA1 and NA2 granulocytes human alloantigen type. Rarely these young patients present serious infections despite severe neutropenia

How to manage neutropenic patients?

Laboratory explorations to determine the etiology are depicted in (table III). When a drug-related neutropenia is suspected, medication has to be suspended. In febrile patients, empirical broad-spectrum antibiotics are needed after blood, urine, and site-specific cultures. G-CSF is commonly used especially in patients with poor prognostic factors, such as bacteremia, renal insufficiency, advanced age, very low neutrophil count, bone marrow hypoplasia and shock even if the only comparative study

Conclusions

The diagnosis of autoimmune neutropenia is based on the presence of anti-neutrophil antibodies associated neutropenia. The spectrum of the disease includes primary, secondary autoimmune neutropenia and drug-induced immune neutropenia in adult patients. Laboratory diagnostic tests are not easily detected and have to be repeated over time. G-CSF is the first treatment option for AIN. Immunosuppressive agents are proposed for chronic AIN, especially in the context of underlying autoimmune

Disclosure of interest

the authors declare that they have no conflicts of interest concerning this article.

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