CLINICAL CONSEQUENCES AND TREATMENT OF PRIMARY IMMUNODEFICIENCY SYNDROMES CHARACTERIZED BY FUNCTIONAL T-LYMPHOCYTE AND B-LYMPHOCYTE ANOMALIES (COMBINED IMMUNE-DEFICIENCY)

Objective. To review the clinical presentation and outcome of patients with an unusual primary T + B lymphocyte immunodeficiency syndrome, c haracterized by the presence of T lymphocytes with no detectable gross phenotypic anomaly, but which are not activated in vitro or in vivo i n response to antigens, although they do respond to mitogens. Methods. A retrospective analysis of clinical and immunological data recorded in 25 cases. Acquired immunodeficiencies and known primary T cell immu nodeficiency syndromes (severe combined immunodeficiency syndrome, Di- George syndrome, Wiskott-Aldrich syndrome, cartilage hair hypoplasia, Omenn's syndrome, ataxia telangiectasia, defective expression of major histocompatability complex class II molecules, and defective expressi on of the CD3/T cell receptor complex) were excluded. Results. The pat ients had severe and particularly protracted infections, mainly of the respiratory tract and gut. Severe viral infections, generally due to herpes viruses, occurred in nearly two-thirds of the patients, with a median follow-up of 54 months. Autoimmune manifestations are frequent (60%), targetting mainly marrow-derived cells, and were characterized by a tendency to relapse and by a dependence on immunosuppressive ther apy. Allergic manifestations were also frequent (48% of cases). Eight of the 19 patients who had not undergone bone marrow transplantation d ied. All but one of the 11 survivors had moderate to severe sequelae. Bone marrow transplantation seemed to be the treatment of choice, beca use four of six recipients of HLA-identical (n = 2) or nonidentical (n = 4) marrow are alive and the immune deficiency has been corrected. C onclusion, Early recognition of these life-threatening syndromes may i mprove the chances of cure. Despite common clinical manifestations and prognosis, these functional immunodeficiencies appear heterogeneous r egarding inheritance pattern and at least existence of a B cell immuno deficiency.