Evaluation of Phagocytic Component of the Immune System in Patients with Organic Acidemia

Abstract

Background: There are several reports of recurrent infections in patients with organic acidemia. Almost all studies on the immune system of these patients have investigated the immune system in the acidotic phase of the disease. In the present study, the phagocytic component of the immune system was evaluated in patients with organic acidemia. Methods: After exclusion of patients in the acidotic phase of the disease, 31 patients with organic acidemia were included in the study. All patients completed the written informed consents, and the study was approved by the ethics committee of Mofid Children's hospital. Information including age, sex, type of organic acidemia, and history of hospitalization due to infection was recorded. Screening tests of phagocytic component of the immune system, including total and differential white blood cell (WBC) count and nitroblue tetrazolium (NBT) test, were performed for all the patients. Results: The prevalence of neutropenia was high among patients (22.6%); it was even more frequent in patients younger than 3 years (42.6%). On the other hand, in most patients (93.5%), neutrophils showed normal function on the NBT test. Conclusions: Neutropenia in the nonacidotic phase of organic acidemia can be the cause of recurrent infections in these patients. It can be independent of bone marrow suppression, caused by reduced production of these cells as a result of reduced pH in the acidotic phase of the disease.

Altered immune response in organic acidemia

“…Hence, it is not surprising that some patients may exhibit neutropenia and associated immune dysfunctions constantly. 1,4,10,13 Deep-tissue infections, gingivitis and sepsis are frequently seen in patients with neutropenia, which is compatible with our results. 24 Unlike neutrophils, lymphocyte counts did not differ among groups (P = 0.536).…”

“…9 Although neutropenia is more pronounced during a metabolic attack, Alaei et al documented neutropenia in 22.5% of their patients during nonacidotic phase. 10 It is well known that patients with OAs are shown to excrete toxic metabolites in urine and blood, even during non-acidotic phases. Hence, it is not surprising that some patients may exhibit neutropenia and associated immune dysfunctions constantly.…”

“…25 Memory B cells continue to produce a constant level of antibodies providing immediate protection if a re-exposure to this antigen occurs. 10 Decreased memory B cells are frequently seen in various PIDs, resulting in recurrent sinopulmonary infections. 25 The failure of memory B cell generation may be a predisposing factor for recurrent infections in OAs.…”

“…Blood count abnormalities such as neutropenia are well-known features of OAs. 10,15,22,23 However, a little less is known about the immunological properties of these patients. To answer this question, we evaluated the adaptive immune systems of these patients by measuring immunoglobulin levels and lymphocyte subtypes during infection free periods.…”

“…1,8,9 Various immunological abnormalities have also been described in patients with OAs presenting with recurrent infections, such as hypogammaglobulinemia, and various B and/or T-cell defects. [10][11][12] However, besides case reports, these associations have not been studied thoroughly. [13][14][15][16][17] To address this question, we aimed to assess the immunological profile of OA patients during infection-free periods.…”