Published Online: February 28, 2013
Severe combined immunodeficiency (SCID) is a primary immunodeficiency characterized by profound impairment in antibody synthesis and cellular immune function. With an estimated incidence of 1 in 50,000 to 1 in 100,000 live births, SCID is uniformly fatal within the first year of life if left untreated. Screening for SCID using measurement of T-cell receptor excision circles (TRECs) was added to the National Uniform Newborn Screening (NBS) program in May 2010 to identify newborns for further evaluation. In California, where it was implemented in August 2010, TREC analysis has been reportedly effective in detecting all SCID cases born in the state to date.
Major Histocompatibility Class (MHC) II deficiency is a rare autosomal-recessive form of combined immunodeficiency (CID) characterized by a defect in the expression of HLA-DR on immune cells. In a Letter to the Editor published recently in The Journal of Allergy & Clinical Immunology (JACI), Kuo et al report two infants with MHC II deficiency missed by NBS, because their TREC levels were well above the established cutoff. Both patients presented at less than 7 months of age with failure to thrive, intractable diarrhea, and severe respiratory infections. Their immunologic workups were similar with normal total lymphocyte counts but selective CD4+ lymphopenia, depressed in vitro lymphocyte function, and reduced HLA-DR expression on peripheral blood lymphocytes. One of the infants died shortly after hematopoietic stem cell transplant and the other was deemed not a candidate due to additional congenital defects.
These cases emphasize a group of CIDs in which T-lymphopenia is not a feature, yet the impairment of immune function is as profound as in patients with classical SCID. Despite severe T cell dysfunction, MHCII-deficient patients still have significant numbers of circulating T cells and will therefore be missed by the cutoff value of TRECs currently in place. The authors’ observations suggest that alternative screening strategies would need to be developed to identify this subset of primary immunodeficiencies and to provide early and potentially curable interventions.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.