SEVERE COMBINED IMMUNODEFICIENCY WITH CARTILAGE HAIR HYPOPLASIA - INVITRO RESPONSE TO THYMOSIN AND ATTEMPTED RECONSTITUTION

A case was reported of 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 mo. of age following a history of recurrent severe infection. Family history included 3 cousins who died in early infancy, 1 from streptococcal meningitis and pneumonia, 1 from generalized varicella and another from reticuloendotheliosis. Quantitative immunoglobulins [Ig] 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 [erythrocyte] 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 .mu.g thymosin. Blastogenic responses to phytohemagglutinin also increased in the presence of thymosin. Transplantation of 24 wk fetal thymus in Millipore diffusion chambers and subsequently transplantation of 18 wk fetal thymus by i.p. injection was accomplished. E rosettes increased to 35-40% and blastogenic responses to mitogens increased. Eight days after the 2nd transplant the patient underwent a mild graft vs. host reaction which subsided after 1 wk 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 mo. after transplantation.