First report of the hyper-IgM syndrome registry of the latin american society for immunodeficiencies: Novel mutations, unique infections, and outcomes
Por:
Cabral-Marques O., Klaver S., Schimke L.F., Ascendino E.H., Khan T.A., Pereira P.V.S., Falcai A., Vargas-Hernández A., Santos-Argumedo L., Bezrodnik L., Moreira I., Seminario G., Di Giovanni D., Raccio A.G., Porras O., Weber C.W., Ferreira J.F., Tavares F.S., De Carvalho E., Valente C.F.C., Kuntze G., Galicchio M., King A., Rosário-Filho N.A., Grota M.B., Dos Santos Vilela M.M., Di Gesu R.S.W., Lima S., De Souza Moura L., Talesnik E., Mansour E., Roxo-Junior P., Aldave J.C., Goudouris E., Pinto-Mariz F., Berrón-Ruiz L., Staines-Boone T., Calderón W.O.C., Del Carmen Zarate-Hernández M., Grumach A.S., Sorensen R., Durandy A., Torgerson T.R., Carvalho B.T.C., Espinosa-Rosales F., Ochs H.D., Condino-Neto A.
Publicada:
1 ene 2014
Resumen:
Hyper-IgM (HIGM) syndrome is a heterogeneous group of disorders characterized by normal or elevated serum IgM levels associated with absent or decreased IgG, IgA and IgE. Here we summarize data from the HIGM syndrome Registry of the Latin American Society for Immunodeficiencies (LASID). Of the 58 patients from 51 families reported to the registry with the clinical phenotype of HIGM syndrome, molecular defects were identified in 37 patients thus far. We retrospectively analyzed the clinical, immunological and molecular data from these 37 patients. CD40 ligand (CD40L) deficiency was found in 35 patients from 25 families and activation-induced cytidine deaminase (AID) deficiency in 2 unrelated patients. Five previously unreported mutations were identified in the CD40L gene (CD40LG). Respiratory tract infections, mainly pneumonia, were the most frequent clinical manifestation. Previously undescribed fungal and opportunistic infections were observed in CD40L-deficient patients but not in the two patients with AID deficiency. These include the first cases of pneumonia caused by Mycoplasma pneumoniae, Serratia marcescens or Aspergillus sp. and diarrhea caused by Microsporidium sp. or Isospora belli. Except for four CD40L-deficient patients who died from complications of presumptive central nervous system infections or sepsis, all patients reported in this study are alive. Four CD40L-deficient patients underwent successful bone marrow transplantation. This report characterizes the clinical and genetic spectrum of HIGM syndrome in Latin America and expands the understanding of the genotype and phenotype of this syndrome in tropical areas. © 2014 Springer Science+Business Media New York.
Filiaciones:
Cabral-Marques O.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
Klaver S.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
Schimke L.F.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
Ascendino E.H.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
Khan T.A.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
Pereira P.V.S.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
Falcai A.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
Vargas-Hernández A.:
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados-IPN Zacatenco, México D.F, Mexico
Santos-Argumedo L.:
Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados-IPN Zacatenco, México D.F, Mexico
Bezrodnik L.:
Dr. Ricardo Gutierrez Children's Hospital, Immunology, Buenos Aires, Argentina
Moreira I.:
Dr. Ricardo Gutierrez Children's Hospital, Immunology, Buenos Aires, Argentina
Seminario G.:
Dr. Ricardo Gutierrez Children's Hospital, Immunology, Buenos Aires, Argentina
Di Giovanni D.:
Dr. Ricardo Gutierrez Children's Hospital, Immunology, Buenos Aires, Argentina
Raccio A.G.:
Dr. Ricardo Gutierrez Children's Hospital, Immunology, Buenos Aires, Argentina
Porras O.:
Hospital Nacional de Niños, Dr. Carlos Sáenz Herrera, San Jose, Costa Rica
Weber C.W.:
Pediatric Allergy and Immunology Clinic, Caxias do Sul RS, Brazil
Ferreira J.F.:
Albert Sabin Hospital, Fortaleza CE, Brazil
Tavares F.S.:
Pediatric Immunology Clínic, Hospital de Base Do Distrito Federal, Brasilia DF, Brazil
De Carvalho E.:
Pediatric Immunology Clínic, Hospital de Base Do Distrito Federal, Brasilia DF, Brazil
Valente C.F.C.:
Pediatric Immunology Clínic, Hospital de Base Do Distrito Federal, Brasilia DF, Brazil
Kuntze G.:
Integrated Center of Pediatric Specialties, Curitiba PR, Brazil
Galicchio M.:
Hospital de Niños V. J. Vilela, Rosario, Argentina
King A.:
Hospital Luis Calvo Mackenna, Santiago, Chile
Rosário-Filho N.A.:
Department of Pediatrics, Federal University of Paraná, Curitiba PR, Brazil
Grota M.B.:
Department of Pediatrics, State University of Campinas Medical School, Campinas SP, Brazil
Dos Santos Vilela M.M.:
Department of Pediatrics, State University of Campinas Medical School, Campinas SP, Brazil
Di Gesu R.S.W.:
Division of Allergy and Immunolgy, Department of Pediatrics, Conceição Children's Hospital, Porto Alegre RS, Brazil
Lima S.:
Childrens Hospital Lucídio Portela, Teresina PI, Brazil
De Souza Moura L.:
Childrens Hospital Lucídio Portela, Teresina PI, Brazil
Talesnik E.:
Division of Pediatrics, Pontificia Universidad Católica de Chile, Santiago, Chile
Mansour E.:
Department of Medicine, State University of Campinas Medical School, Campinas SP, Brazil
Roxo-Junior P.:
Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto SP, Brazil
Aldave J.C.:
Hospital Nacional Edgardo Rebagliati Martins-Alergia e Inmunologia, Lima, Peru
Goudouris E.:
Department of Pediatrics, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Pinto-Mariz F.:
Department of Pediatrics, School of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Berrón-Ruiz L.:
Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatría, México D.F, Mexico
Staines-Boone T.:
Unidad Médica de Alta Especialidad 25, IMSS, Monterrey Nuevo León, Mexico
Calderón W.O.C.:
Unidad de Inmunología, Clínica Montefiori, Lima, Peru
Del Carmen Zarate-Hernández M.:
Hospital Universitario, U.A.N.L, Monterrey Nuevo León, Mexico
Grumach A.S.:
Faculty of Medicine ABC, Santo-André SP, Brazil
Sorensen R.:
Department of Pediatrics, Children's Hospital, New Orleans, LA, United States
Durandy A.:
INSERM, Unité U768, Hôpital Necker Enfants-Malades, Paris, France
Torgerson T.R.:
Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Research Institute, Seattle, WA, United States
Carvalho B.T.C.:
Division of Allergy-Immunology and Rheumatology, Department of Pediatrics, Federal University of São Paulo, São Paulo, Brazil
Espinosa-Rosales F.:
Unidad de Investigación en Inmunodeficiencias, Instituto Nacional de Pediatría, México D.F, Mexico
Ochs H.D.:
Department of Pediatrics, University of Washington School of Medicine, Seattle Children's Research Institute, Seattle, WA, United States
Condino-Neto A.:
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 1730 Lineu Prestes Avenue, São Paulo SP 05508-000, Brazil
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