Clinical Presentation, Immunologic Features, and Hematopoietic Stem Cell Transplant Outcomes for IKBKB Immune Deficiency

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2018 Nov 5

PMID 30391351

Citations 9

Authors

Geoffrey D E Cuvelier

Tamar S Rubin

Anne Junker

Roona Sinha

Alan M Rosenberg

Donna A Wall

Marlis L Schroeder

Affiliations

Soon will be listed here.

Abstract

IKBKB immune deficiency is a rare but life-threatening primary immunodeficiency disorder, involving activation defects in adaptive and innate immunity. We present sixteen cases of a homozygous IKBKB mutation (c.1292dupG) in infants characterized by early-onset bacterial, viral, fungal and Mycobacterial infections. In most cases, T- and B-cells were quantitatively normal, but phenotypically naïve, with severe hypogammaglobulinemia. T-cell receptor excision circles were normal, meaning newborn screening by TREC analysis would miss IKBKB cases. Although IKBKB immune deficiency does not meet traditional laboratory based definitions for SCID, this combined immune deficiency appears to be at least as profound. Urgent HSCT, performed in eight patients, remains the only known curative therapy, although only three patients are survivors. Ongoing infections after transplant remain a concern, and may be due to combinations of poor social determinants of health, secondary graft failure, and failure of HSCT to replace non-hematopoietic cells important in immune function and dependent upon IKK/NF-κB pathways.

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