RESUMEN
We report the clinical and immunologic features and outcome in 56 patients with X-linked hyper-IgM syndrome, a disorder caused by mutations in the CD40 ligand gene. Upper and lower respiratory tract infections (the latter frequently caused by Pneumocystis carinii), chronic diarrhea, and liver involvement (both often associated with Cryptosporidium infection) were common. Many patients had chronic neutropenia associated with oral and rectal ulcers. The marked prevalence of infections caused by intracellular pathogens suggests some degree of impairment of cell-mediated immunity. Although lymphocyte counts and in vitro proliferation to mitogens were normal, a defective in vitro proliferative response to antigens was observed in some patients, and additional defects of cell-mediated immunity may be presumed on the basis of current knowledge of CD40-ligand function. All patients received regular infusions of immunoglobulins. Four patients underwent liver transplantation because of sclerosing cholangitis, which relapsed in there. Three patients underwent bone marrow transplantation. Thirteen patients (23%) died of infection and/or liver disease. X-linked hyper-IgM syndrome, once considered a clinical variant of hypogammaglobulinemia, is a severe immunodeficiency with significant cellular involvement and a high mortality rate.
Asunto(s)
Ligamiento Genético , Hipergammaglobulinemia/genética , Inmunoglobulina M , Síndromes de Inmunodeficiencia/genética , Cromosoma X , Trasplante de Médula Ósea , Antígenos CD40/genética , Causas de Muerte , Niño , Preescolar , Enfermedad Crónica , Criptosporidiosis/fisiopatología , Diarrea/fisiopatología , Humanos , Hipergammaglobulinemia/inmunología , Hipergammaglobulinemia/fisiopatología , Hipergammaglobulinemia/terapia , Inmunidad Celular/genética , Inmunidad Celular/fisiología , Inmunoglobulina M/administración & dosificación , Inmunoglobulina M/uso terapéutico , Síndromes de Inmunodeficiencia/inmunología , Síndromes de Inmunodeficiencia/fisiopatología , Síndromes de Inmunodeficiencia/terapia , Lactante , Recién Nacido , Ligandos , Hepatopatías/fisiopatología , Trasplante de Hígado , Activación de Linfocitos/inmunología , Recuento de Linfocitos , Mutación/genética , Neutropenia/fisiopatología , Infecciones Oportunistas/fisiopatología , Úlceras Bucales/fisiopatología , Neumonía por Pneumocystis/fisiopatología , Enfermedades del Recto/fisiopatología , Infecciones del Sistema Respiratorio/fisiopatología , Resultado del Tratamiento , Úlcera/fisiopatología , Cromosoma X/genéticaRESUMEN
Fourteen S/S children with severe SCD were transplanted with marrow from HLA identical siblings. All developed frequent (> 4/y) vasoocclusive crises (VOC) and recurrent acute chest syndrome episodes (n:10), osteitis (n:3), osteonecrosis (n:3), strokes (n:3) or frequent massive deglobulisation (n:2). Two children undergone splenectomy, 2 were chelated and 2 had erythroid allo-immunization. Ethnic origins were from various countries in Africa (n:10), North-Africa (n:3) or West Indies (n:1). At BMT, they were 2y 3m to 14y 9m old (mean:8y 7m). Donors were AS (n:11) or AA (n:3). At first, various conditioning regimens were used consisting of busulfan (BU) plus Cyclophosphamide (CY) at different doses: CY:200 mg/kg (n:12) or 260 mg/kg (n:2); BU:14 mg/kg (n:1), 16 mg/kg (n:9), > 16 mg/kg (n:4); 1 patient received also TLI and one other antithymoglobulin (ATG): 20 mg/kg. GVHD prophylaxis was CSA alone (n:4) or CSA plus short-term MTX (n:10). Median follow-up was 23 months (8 m. to 48 m.). All patients had an engraftment (d13 to d32) with a stable total chimerism in 10/14 patients who are cured. In the 4 others, partial chimerism was observed: one patient had a early and progressive rejection of his graft but is doing very well (28 m. follow-up) without any manifestation of SCD, with a high stable 22% Hb F level. One patient developed an aplastic anaemia 15 m after BMT: a second BMT was achieved 21 m after the first one with engraftment and total chimerism. Two patients have a relatively stable partial chimerism with still undergoing CSA therapy (11 m. and 23 m. follow-up).(ABSTRACT TRUNCATED AT 250 WORDS)