Major Histocompatibility Complex Class II Deficiency due to a Novel Mutation in RFXANK in a Child of Mexican Descent

To the Editor: Major histocompatibility (MHC) Class II molecules (alternatively known as human leukocyte antigens (HLAs)) allow presentation of exogenous peptides to the T-cell receptor of CD4 T helper cells, and are essential in the development of a normal adaptive immune response. Mutations in the genes encoding the MHC class II transactivator (CIITA), regulatory factor X-associated protein (RFXAP), regulatory factor X, 5 (RFX5), and ankyrin repeat-containing regulatory factor X (RFXANK) [1, 2] have been associated with the phenotype of bare lymphocyte syndrome. Here, we describe the case of a previously healthy, Hispanic male who presented at 4 months of age with a progressive respiratory infection. He was born at full term to a 39 year old gravida 3, para 3 with an uneventful perinatal course. He received all age-appropriate immunizations including hepatitis B, diphtheria, pertussis, tetanus,Haemophilus influenzae type B, polio, and pneumococcal conjugate vaccine without issues. He had not received any live vaccines. He was born to parents of Mexican descent who were related (4th generation). Two older siblings were healthy without history of immunodeficiency. At the age of four months he was diagnosed with acute otitis media, which was treated with amoxicillin. Despite antibiotics, he developed progressive respiratory symptoms as well as diffuse rash, leading to hospitalization and treatment of presumed pneumonia with antibiotics. He developed a gradually increasing oxygen requirement in spite of antibiotics, steroids, and diuretic therapy, with acute worsening on day 10 of admission requiring intubation. Laboratory evaluation showed negative viral PCR testing for influenza and respiratory syncytial virus, and nasopharyngeal PCR that was positive for a picornavirus. Quantitative PCRs for cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV) were negative from blood. Bacterial and fungal cultures from blood and lower respiratory samples did not reveal a causative organism. Evaluation by otorhinolaryngology did not show anatomic airway abnormalities. Chest X-ray revealed interstitial pneumonia and a pneumomediastinum, which were suggestive of Pneumocystis jiroveci. Lactate dehydrogenase and beta-D glucan were elevated at 845 Units/L (normal 135–376 U/L) and 424 pg/mL (normal <60 pg/ml) respectively, which further supported the diagnosis of Pneumocystis pneumonia. Initial immunologic evaluation showed neutropenia, panhypogammaglobulinemia, and moderate T-cell lymphocytopenia with near absent lymphocyte proliferation in response to mitogen phytohemagluttinin (PHA) as well as to Tetanus and Candida antigens (Supplemental Table 1). He had normal neutrophil oxidative activity by dihydrorhodamine assay. Electronic supplementary material The online version of this article (doi:10.1007/s10875-015-0219-4) contains supplementary material, which is available to authorized users.