Challenges in the use of allogeneic hematopoietic SCT for ectodermal dysplasia with immune deficiency

Genetic mutations of proteins regulating nuclear factor of κ-light polypeptide gene enhancer in B lymphocyte (NF-κB) activation result in heritable diseases of development and immunity. Hypomorphic, X-linked mutations in the IKBKG gene (NF-κB essential modulator (NEMO) protein), and hypermorphic, autosomal dominant mutations in the IKBA gene (inhibitor of NF-κB (IκB)-α protein), are associated with a phenotype of immune deficiency and often ectodermal dysplasia (ED-ID). ED-ID predisposes patients to recurrent and life-threatening infections and is typically fatal within the first few years of life. Allogeneic hematopoietic SCT (HSCT) may correct the immune deficiency associated with NEMO or IκBα mutations, but there is very little published data. We gathered clinical data on three ED-ID patients that had undergone HSCT. Conditioning regimens were variable, as were the stem cell sources. All three patients experienced engraftment difficulties as well as post transplant complications. These cases suggest that patients with immune deficiencies caused by NEMO or IκBα mutations may have intrinsic barriers to successful engraftment, which require further investigation.