Autoimmune Neutropenias: Update on Clinical and Biological Features in Children and Adults

Abstract

The definition of autoimmune neutropenias (AIN) has been based on the demonstration of autoantibodies directed to various epitopes on blood neutrophils. However, this definition is probably too limited and excludes neutropenias (NPs) with a negative autoantibody test but with other phenomena that indicate an underlying autoimmune process. Examples of such AINs may be complete or incomplete systemic lupus erythematosus or other autoimmune diseases where NP is common but patients may not fulfill formal diagnostic criteria for a rheumatic disease. Recently, various inherited immune-dysregulation syndromes, such as those related to variants in, for example, TACI, BAFFR, ACKR1/DARC, LRBA, CTLA 4 genes, with dysregulated B- and T-lymphocyte functions, have been associated with concomitant AINs. Cellular immune mechanisms may also play a prominent role in the development of NP, in the presence or not of autoantibodies, in cases of large granular lymphocyte syndromes of T- and NK-cell types or in chronic idiopathic NP, particularly in adults with T-cell clonal populations. The course of AIN may differ according to age, being transient and rather uncomplicated in children, and chronic with treatment requirement in adolescents and adults. This review discusses current knowledge of AINs, including diagnostic procedures, treatments, and prognosis.

The Clinical Course of SARS-CoV-2 Infection in Patients With Autoimmune Neutropenia: A Retrospective Case Series Study

“…The reason for the improvement in neutrophil values in the weeks following infection could lie in the alterations induced by COVID-19 on regulatory cell homeostasis and in lymphopenia itself, which could transiently reduce the production of autoantibodies responsible for the destruction of peripheral neutrophils. 3,5 Finally, in patients with atypical autoimmune neutropenia (as defined in the recent literature 2 ), SARS-CoV-2 infection also occurred in a mild form with a similar impact on ANC and ALC values. This retrospective study has many limitations.…”

“…2 In any case, the main mechanism of neutrophil reduction seems to be related to the presence of antibodies that cause peripheral cell destruction by binding to membrane antigens such as IgG type 3b Fc receptor (FcγIIIb receptor). 3 Some alternative mechanisms involving cellular immunity and Treg cells have been proposed. 3 However, the pathogenesis of AIN is still not entirely clear.…”

“…3 Some alternative mechanisms involving cellular immunity and Treg cells have been proposed. 3 However, the pathogenesis of AIN is still not entirely clear.…”

The European Guidelines on Diagnosis and Management of Neutropenia in Adults and Children: A Consensus Between the European Hematology Association and the EuNet-INNOCHRON COST Action

“…In adults, antineutrophil antibodies can be found in primary and secondary AIN. 1,12,35 It is particularly important to exclude the presence of alloantibodies again HLA class I, which are common in transfused patients and previously pregnant women and can give false-positive GIFT results. 19 An independent analysis of HLA class I antibodies, and/or confirmation of the specificity of the granulocyte antibodies using MAIGA test or GIFT with genotyped neutrophils, is therefore recommended before positive antibody results are conclusively interpreted.…”

Splenectomy outcomes in immune cytopenias: Treatment outcomes and determinants of response

“…This decline can be attributed to challenges in identifying individual likelihood to respond to this invasive procedure and concerns related to infection risks [14,15] to the extent that British recommendations have now positioned splenectomy as a third-line treatment option [16]. Conversely, there are no clear guidelines regarding the timing of splenectomy in AIN [17].…”