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Thursday, April 6, 2017

A prospective study on the natural history of patients with profound combined immunodeficiency (P-CID): an interim analysis

The immune system is complex, composed of numerous cells, proteins, and other components.  Among them, the T-cells are essential in fighting off infectious agents and regulating the functions of the immune system.  People with reduced or dysfunctional T-cells can have life-threatening complications, and may require interventions like hematopoietic stem cell transplant (HSCT), gene therapy, or enzyme replacement. If a T cell deficiency is severe (severe combined immunodeficiency, SCID), these treatment decisions are clear. However, in patients with moderate T cell deficiency (profound combined immunodeficiency, P-CID), prognosis is unclear and transplant decisions are difficult. These patients have so far received little attention.  In this month’s issue of JACI, Speckmann and colleagues report the first 51 P-CID patients  enrolled in a long-term prospective study (J Allergy Clin Immunol 2017; 139(4): 1302-1310). The patients suffer from heterogenous T cell deficiencies including: (1) ‘bona fide’ CID, where deficiencies are typically associated with profound T-cell deficiencie, (2) atypical severe combined immunodeficiency (SCID), in which T-cell dysfunction is due to less life-threatening mutations in SCID-associated genes, and (3) T cell deficiencies with genetically unidentified cause.  They analyzed  the clinical and molecular characteristics at study entry to determine disease severity.  Ultimately, the aim is to identify parameters predicting  when the risks of untreated disease outweigh the risks of performing HSCT.

They found that patients with P-CID have a high rate of morbidity and mortality as well as a lower quality of life.  One-third of patients underwent HSCT within the first year of inclusion into the study, 5 patients died.  The genetic diagnosis has limited value as a predictor of disease evolution and thus as a guidance for HSCT decisions, with the age of onset, quality of life, and severity of disease not significantly different between patients with atypical SCID, bona fide CVID, or genetically undefined disease.  This was in line with the authors’ expectations, but what they didn’t expect was that basic measures of T-cell immunity also did not predict the prognosis and course of their disease.

Speckmann and colleagues continue to enroll patients and hope to eventually reach their target of 120.  Parallel long-term follow-up of transplanted and of non-transplanted patients will better identify predictors for the natural progress of P-CID, and, in turn, give better guidance about how, and when, to treat with HSCT.

1 comment:

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