Neutropenia among patients with adenosine deaminase deficiency

Abstract

(ADA) is a ubiquitous enzyme important for the degradation and salvage of adenosine (Ado) and deoxyAdo (dAdo). Autosomal-recessive defects that severely disrupt the function of ADA lead to accumulation of purine metabolites, which are toxic for rapidly proliferating cells, such as lymphocytes. 1 Most ADA-deficient patients present in the first year of life with profound T-and B-cell defects, leading to severe combined immunodeficiency (SCID). In addition, ADA-deficient patients frequently suffer from liver, lungs, bone, and other tissues abnormalities. 1 Management of ADA deficiency includes supportive care with antimicrobials such as trimethoprim/ sulfamethoxazole (TMP-SMZ) and immunoglobulins. Enzyme replacement therapy (ERT) with polyethylene-glycol-conjugated ADA can improve purine homeostasis and may serve as a ''bridge'' until patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) or gene therapy (GT). HSCT using healthy HLA-matched or mismatched family-related or unrelated donors can correct the immune and some of the systemic abnormalities. 2 Myelodysplasia has previously been reported among ADA-deficient patients; however, because most patients were after unsuccessful HSCT or GT, the role of the metabolic abnormality was not clear. 3 Here, we tested the hypothesis that ADA deficiency could be directly associated with myeloid abnormalities and neutropenia. We analyzed data from all 20 patients diagnosed at our center

Neutropenia as a sign of immunodeficiency

“…Yet they are often out of the purview of immunologists because the neutropenia corrects with metabolic intervention, and immunologists are often not involved. Nevertheless, the article by Kim et al 1 represents a reminder of the importance of this category of neutropenic conditions. Tables I and II list the recognized causes of neutropenia and provide a framework for their conceptualization.…”

“…Kim et al 1 have drawn attention to a finding that might forge greater collaboration between hematologists and immunologists and has served as a potent reminder of an oft-neglected category of neutropenia. Additional studies might determine whether the neutropenia in patients with these immunodeficiencies affects outcomes.…”

Comparison of elapegademase and pegademase in ADA-deficient patients and mice

“…Inherited defects in the ADA gene cause severe combined immune deficiency (ADA–SCID) with progressive decline in the number of T, B and natural killer (NK) lymphocytes leading to increased susceptibility to infections . In addition, ADA–SCID patients might develop skeletal dysplasia, manifesting primarily in scapular spurring and costo‐chondral cupping , developmental delay , sensory‐neural hearing defects respiratory distress , hepatic failure and neutropenia . Allogeneic hematopoietic stem cell transplants (HSCT) from ADA‐proficient donors or hematopoietic stem cell gene therapy (HSC‐GT) using the patients’ own cells that were transduced with a normal ADA gene can correct the immune and systemic abnormalities associated with ADA–SCID.…”

Specific immunological areactivity formation during gestation period in pregnant sows

“…Immunological reactivity changes to viral and bacterial antigens may cause increased susceptibility to infectious diseases. Different levels of this condition in newborn and adult animal organisms should be based on the fact that the fetus and newborn after birth first comes into contact with the antigen, while the adult body already has partial sensitization [1][2][3], [12][13][14][15]. Chronic carrier of pathogens in animals and their influence on the spread of the infectious process is an urgent problem of modern veterinary medicine.…”