Severe Combined Immunodeficiency with Cartilage-Hair Hypoplasia: In Vitro Response to Thymosin and Attempted Reconstitution

Abstract

The present report describes an infant with severe combined immunodeficiency and cartilage-hair hypoplasia whose lymphocytes responded to thymosin in vitro. Immunologic evaluation was undertaken at 4 1/2 months of age following a history of recurrent severe infection. Family history included three cousins who died in early infancy, one from streptococcal meningitis and pneumonia, one from generalized varicella, and another from reticuloendotheliosis. Quantitative immunoglobulins were markedly depressed: IgG 141, IgA 0, and IgM 24 mg/100 ml. There was an absolute lymphopenia, multiple skin tests were negative, and in vitro lymphocyte responses to mitogens and antigens were depressed. Spontaneous E rosette determinations were 21% compared with control values of 65.7%. Erythrocyte adenosine deaminase (ADA) activity was normal. The patient's E rosette formation increased in the presence of thymosin, fraction 5, reaching a maximum of 56% with a concentration of 500 mug thymosin. Blastogenic responses to phytohemagglutinin also increased in the presence of thymosin. Transplantation of 24-week fetal thymus in Millipore diffusion chambers and subsequently transplantation of 18-week fetal thymus by intraperitoneal injection was accomplished. E rosettes increased to 35-40% and blastogenic responses to mitogens increased. Eight days after the second transplant the patient underwent a mild graft vs. host reaction which subsided after 1 week and mitogen blastogenic responses again increased to 5-8 times previous values, but still well below control ranges. Repeated episodes of pulmonary infection ensued, cor pulmonale resulted, and the clinical course was relentlessly downhill with the patient expiring from respiratory failure 5 months after transplantation.