Screening for B cell, T cell and natural killer cell defects among children with methylmalonic and propionic acidemias

Abstract

Background: Patients with methylmalonic acidemias (MMAs) and propionic acidemias (PAs) were noticed to suffer recurrent infections with high morbidity and mortality during infections. Neutropenia, impaired phagocytic chemotaxis, low levels of IgG, and depletion of B and T cells in patients with PA and MMA have been previously reported, but relevant studies were limited and based on case reports or small cohorts, with contradictory results. We sought to evaluate B cells, T cells, and natural killer (NK) cells in children with MMA and PA and investigate the impact of metabolic disease control on the studied immunological parameters. Thirty patients (23 MMAs and 7 PAs) were enrolled in a cross-sectional study. Patients were subjected to clinical evaluation, complete blood count, blood gases, serum immunoglobulin levels, candida intradermal testing, and lymphocyte subset flow cytometric enumeration. Results: Patients’ ages ranged between 6 and 86 months (mean 37.93 ± 23.2 SD). BCG scar was elicited in 24/26 (92.3%) of vaccinated patients. Candida test was positive in 12 (85.7%) out of 14 tested patients. Four patients had neutropenia (13.3%), 1 had lymphopenia (3.3 %), 17 had low absolute CD19+ counts (56.7%), 5 had low absolute CD27+ counts (16.7%), 14 had low CD3+ counts (46.7%), 9 had low CD4+ counts (30%), 8 had low CD8+ counts (26.7%), 12 had decreased CD4/CD8 ratio (40%), and 8 had low CD56+ counts (26.7%). All patients had normal serum immunoglobulins. Metabolically controlled and uncontrolled cases were comparable in terms of their candida test results and lymphocyte subsets. Conclusion: Patients with MMA or PA are prone to neutropenia, decreased B and T cells with low CD4+/CD8+ ratio, and decreased NK cells, yet with normal serum immunoglobulins and candida intradermal test results. We could not find a relation between the immunological results and the degree of metabolic disease control.