Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: The Primary Immune Deficiency Treatment Consortium experience - 29/03/14
, Elizabeth Dunn, MA b, Luigi D. Notarangelo, MD c, Christopher C. Dvorak, MD b, Jennifer M. Puck, MD b, Brent R. Logan, PhD d, Linda M. Griffith, MD, PhD e, Donald B. Kohn, MD f, Richard J. O'Reilly, MD g, Thomas A. Fleisher, MD h, Sung-Yun Pai, MD i, Caridad A. Martinez, MD j, Rebecca H. Buckley, MD k, Morton J. Cowan, MD bAbstract |
Background |
The approach to the diagnosis of severe combined immunodeficiency disease (SCID) and related disorders varies among institutions and countries.
Objectives |
The Primary Immune Deficiency Treatment Consortium attempted to develop a uniform set of criteria for diagnosing SCID and related disorders and has evaluated the results as part of a retrospective study of SCID in North America.
Methods |
Clinical records from 2000 through 2009 at 27 centers in North America were collected on 332 children treated with hematopoietic stem cell transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and related disorders. Eligibility for inclusion in the study and classification into disease groups were established by using set criteria and applied by an expert review group.
Results |
Two hundred eighty-five (86%) of the patients were determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible patients, 84% were classified as having typical SCID; 13% were classified as having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID phenotype was accepted for eligibility. Reasons for noneligibility were failure to demonstrate either impaired lymphocyte proliferation or maternal T-cell engraftment. Overall (n = 332) rates of testing were as follows: proliferation to PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in 62%).
Conclusion |
Lack of complete laboratory evaluation of patients before HCT presents a significant barrier to definitive diagnosis of SCID and related disorders and prevented inclusion of subjects in our observational HCT study. This lesson is critical for patient care, as well as the design of future prospective treatment studies for such children because a well-defined and consistent study population is important for precision in outcomes analysis.
Le texte complet de cet article est disponible en PDF.Key words : Allogeneic hematopoietic cell transplantation, gene therapy, primary immunodeficiency, clinical trial
Abbreviations used : ADA, ERT, HCT, PID, PIDTC, SCID, TREC
Plan
| The Primary Immune Deficiency Treatment Consortium (PIDTC) is supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (DAIT-NIAID); the Intramural Research Programs of the National Human Genome Research Institute (NHGRI) and the National Institute of Allergy and Infectious Diseases; and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health (ORDR-NACTS-NIH), Bethesda, Maryland: U54-AI082973 (PI: M. J. Cowan), U54-NS064808 (PI: J. P. Krischer), and R13-AI094943 (PIs: M. J. Cowan and L. D. Notarangelo). This manuscript was presented at the PIDTC Third Annual Scientific Workshop, Houston, Tex, May 2-4, 2013, supported in part by the Immune Deficiency Foundation, Towson, Md; the Jeffrey Modell Foundation, New York, NY; the Robert A. Good Immunology Society, St Petersburg, Fla; the John P. McGovern Foundation, Houston, Tex; the David Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex; Baxter International, Deerfield, Ill; CSL Behring, King of Prussia, Pa; and Sigma-Tau Pharmaceuticals, Gaithersburg, Md. The opinions expressed are those of the authors and do not represent the position of the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, the Office of Rare Diseases Research, the National Center for Advancing Translational Sciences, the National Institutes of Health, or the US Government. |
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| Disclosure of potential conflict of interest: W. T. Shearer has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH; has received travel support from the PIDTC Workshop; is employed by Baylor College of Medicine; and has grants/grants pending with the National Institutes of Health (NIH). E. Dunn has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH; has received travel support from the PIDTC Scientific Workshop; is employed by the University of California–San Francisco (UCSF); and has grants/grants pending from the NIH. L. D. Notarangelo has received research support from the NIH, March of Dimes, and the Jeffrey Modell Foundation; is a board member on the Immune Disease Institute, the Meyer Pediatric Hospital, DMC, Watermark and DMC, NovImmune, Board of Scientific Counselors for the NIAID and NIH, is an Associate Editor for the Journal of Allergy and Clinical Immunology, is an Associate Editor for Clinical Immunology; is employed by Children's Hospital Boston; and receives royalties from UpToDate. C. C. Dvorak has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH and has received travel support from DAIT-NIAID, NHGR NIAID, and ORDR-NCATS-NIH. J. M. Puck has received research support from DAIT-NIAID, NHGRI NIAID, and ORDR-NCATS-NIH; has received travel support from the PIDTC Workshop; is employed by UCSF; has grants/grants pending from the NIH; and receives royalties from a published textbook. B. R. Logan has received research support from the NIAID. L. M. Griffith is a medical officer for the NIAID and is employed by the NIH. D. B. Kohn has received travel support from the PIDTC. R. J. O'Reilly has received research support from the NIAID for the PIDTC and NCI23766, is employed by MSKCC, has provided expert testimony for Miltenyi Biotech, and has patents pending for WT1 peptides. S.-Y. Pai has received grants from DAIT-NIAID, has received support for travel to meetings for study or other purposes from the PIDTC Workshop, is employed by the Boston Children's Hospital, and has grants/grants pending from NIH-Gene Therapy Resource Program. R. H. Buckley has received grants from the NIAID, has received support for travel to meetings from the PIDTC, is employed by the Duke University Medical Center, receives royalties from UpToDate, has stock/stock option in TIAA/CREF, and receives travel expenses from the Foundation for Primary immunodeficiency disease. M. J. Cowan has received research support from DAIT-NIAID, NHGRI NIAID, ORDR-NCATS-NIH, and the NIH; has received travel support to PIDTC workshops; and is employed by the University of California. These authors declare that they have no relevant conflicts of interest. |
Vol 133 - N° 4
P. 1092-1098 - avril 2014 Retour au numéro
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