Complete DiGeorge syndrome: Development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases

• Published in: Journal of allergy and clinical immunology Vol. 113; no. 4; pp. 734 - 741
• Main Authors: Louise Markert, M, Alexieff, Marilyn J, Li, Jie, Sarzotti, Marcella, Ozaki, Daniel A, Devlin, Blythe H, Sempowski, Gregory D, Rhein, Maria E, Szabolcs, Paul, Hale, Laura P, Buckley, Rebecca H, Coyne, Katharine E, Rice, Henry E, Mahaffey, Samuel M, Skinner, Michael A
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.04.2004; Elsevier; Elsevier Limited
• Subjects: Age; Biological and medical sciences; Child, Preschool; Clone Cells - pathology; Defects; Deoxyribonucleic acid; Diabetes; DiGeorge syndrome; DiGeorge Syndrome - complications; DiGeorge Syndrome - pathology; DNA; Exanthema - complications; Fatal Outcome; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gastroesophageal reflux; Hispanic people; Humans; immunodeficiency; Immunopathology; Infant; Infections; Lymphatic Diseases - complications; Lymphocytes; Male; Medical sciences; Ostomy; Patients; Rodents; T cell receptors; T cells; T-Lymphocytes - pathology; thymus; Thymus Gland - abnormalities; transplantation; thymus; DiGeorge syndrome; TCRBV; sjTREC; T cells; SCID; transplantation; ALC; RAG; immunodeficiency; TREC; PCP; CHARGE; Immunopathology; Thymus gland; Transplantation; Immunology; Treatment; Surgery; Adenopathy; T-Lymphocyte; Graft
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.01.766

Five patients with DiGeorge syndrome presented with infections, skin rashes, and lymphadenopathy after the newborn period. T-cell counts and function varied greatly in each patient. Initial laboratory testing did not suggest athymia in these patients. The purpose of this study was to determine whether the patients had significant immunodeficiency. Research testing of peripheral blood included immunoscope evaluation of T-cell receptor β variable gene segment repertoire diversity, quantification of T-cell receptor rearrangement excision circles, and detection of naive T cells (expressing CD45RA and CD62L). The patients were classified as having DiGeorge syndrome on the basis of syndromic associations and heart, parathyroid, and immune abnormalities. Immunoscope evaluation revealed that the T-cell repertoires were strikingly oligoclonal in all patients. There were few recent thymic emigrants, as indicated by the very low numbers of naive T cells (<50/mm3) and the absence of T-cell receptor rearrangement excision circles. These studies showed that all 5 patients were athymic. Two patients died, one from infection. No thymus was found during the complete autopsy performed on one patient. Patients with DiGeorge syndrome, skin rash, and lymphadenopathy should undergo analysis of naive T-cell numbers and of T-cell receptor β variability segment repertoire to determine whether they are athymic, even if they have T cells with mitogen responsiveness. It is important for physicians to realize that patients with complete DiGeorge syndrome remain profoundly immunodeficient after development of these atypical features (rash, lymphadenopathy, and oligoclonal T cells). Prompt diagnosis is necessary for appropriate management.