A prospective study on the natural history of patients with profound combined immunodeficiency: An interim analysis

作者：Speckmann Carsten; Doerken Sam; Aiuti Alessandro; Albert Michael H; Al Herz Waleed; Allende Luis M; Scarselli Alessia; Avcin Tadej; Perez Becker Ruy; Cancrini Caterina; Cant Andrew; Di Cesare Silvia; Finocchi Andrea; Fischer Alain; Gaspar H Bobby; Ghosh Sujal; Gennery Andrew; Gilmour Kimberly; Gonzalez Granado Luis I; Martinez Gallo Monica; Hambleton Sophie; Hauck Fabian; Hoenig Manfred; Moshous Despina; Neven Benedicte; Niehues Tim; Notarangelo Luigi

来源：Journal of Allergy and Clinical Immunology, 2017, 139(4): 1302-+.

DOI：10.1016/j.jaci.2016.07.040

• T-cell deficiency
• combined immunodeficiency
• hematopoietic stem cell transplantation
• natural history

Background: Absent T-cell immunity resulting in life-threatening infections provides a clear rationale for hematopoetic stem cell transplantation (HSCT) in patients with severe combined immunodeficiency ( SCID). Combined immunodeficiencies (CIDs) and "atypical" SCID show reduced, not absent T-cell immunity. If associated with infections or autoimmunity, they represent profound combined immunodeficiency (P-CID), for which outcome data are insufficient for unambiguous early transplant decisions.
Objectives: We sought to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome.
Methods: In this prospective and retrospective observational study, we recruited nontransplanted patients with P-CID aged 1 to 16 years to compare natural histories of severity-matched patients with/without subsequent transplantation and to determine whether immunologic and/or clinical parameters may be predictive for outcome.
Results: A total of 51 patients were recruited (median age, 9.6 years). Thirteen of 51 had a genetic diagnosis of "atypical" SCID and 14 of 51 of CID. About half of the patients had less than 10% naive T cells, reduced/absent T-cell proliferation, and at least 1 significant clinical event/year, demonstrating their profound immunodeficiency. Nineteen patients (37%) underwent transplantation within 1 year of enrolment, and 5 of 51 patients died. Analysis of the HSCT decisions revealed the anticipated heterogeneity, favoring an ongoing prospective matched-pair analysis of patients with similar disease severity with or without transplantation. Importantly, so far neither the genetic diagnosis nor basic measurements of T-cell immunity were good predictors of disease evolution.
Conclusions: The P-CID study for the first time characterizes a group of patients with nontypical SCID T-cell deficiencies from a therapeutic perspective. Because genetic and basic T-cell parameters provide limited guidance, prospective data from this study will be a helpful resource for guiding the difficult HSCT decisions in patients with P-CID.

• 出版日期2017-4
• 单位河北医科大学