Immunodeficiency in patients with Down syndrome: a case series

Introduction:
Down syndrome (DS) is the most common genetic syndrome associated with immune deficiencies in which both innate and adaptive responses are affected. This study reveals the abnormalities in various components of the immune system in patients with DS and their clinical implications.

Case reports:
We present a case series of all patients with DS and immunodeficiency who were evaluated at the pediatric immunology department of a university training/research hospital. As this is a retrospective case series, no ethical committee approval was required. However, informed consent was obtained from each patient for inclusion in this study. Clinical presentation and laboratory tests, including complete blood count, immunoglobulin quantification by nephelometry, and lymphocyte phenotyping by flow cytometry, were evaluated. Additionally, humoral immunity was qualitatively assessed through evaluating specific antibody responses by ELISA to various protein antigens, including antibodies against hepatitis B, Rubella, and Cytomegalovirus, as well as isohemagglutinin titers of the patients.

Results:
Of the patients, 4 were male and 2 were female, with an average age of diagnosis of 59 months. Two patients were diagnosed with transient hypogammaglobulinemia of infancy. The most frequently observed deficiencies among the patients were IgG3 subclass and IgM deficiencies (4 patients), followed by IgA deficiency (3 patients). The least common deficiency was IgG2 (1 patient), while deficiencies in IgG, IgG1, and IgG4 were each identified in 2 patients. Anti-HBs were negative in 4 patients, and anti-Rubella IgG was negative in 1 patient. Low isohemagglutinin titers (< 1/10) were observed in 3 patients. All patients demonstrated reduced absolute counts of CD19+ -B cells, while 4 cases showed percentages below the reference range. Reduced percentages of CD4+ -T cells and CD16+/56+ -NK cells were observed in 1 patient each, and an inverted CD4/CD8 ratio was noted in 2 patients.

Conclusions:
Our patients exhibited B cell lymphopenia. It is becoming evident that immune disorders are an additional concern apart from the well-defined systemic comorbidities in patients with DS. We recommend flow cytometric analysis of lymphocytes in DS patients with recurrent infections.