The International Union of Immunological
Societies [IUIS] published an updated classification in 2011 of primary
immunodeficiency diseases [PID] as part of their on-going work to collate and
disseminate PID research findings reported worldwide. This month, Parvaneh et al. provide a compendium of reports
that have been published since the 2011 update (J Allergy Clin Immunol 2013; 131(2):314-323).
Following the 2011 IUIS classification,
newly published reports are summarized under combined immunodeficiences,
syndromes with associated immunodeficiencies, predominant antibody defects,
immune dysregulation, congenital phagocytic defects, defects of innate
immunity, and autoinflammatory disorders.
Some highlights are provided below.
TCRα gene mutation/TCRαβ T cell
depletion: Two patients from unrelated
Pakistani families were identified after presenting with infection
susceptibility, autoimmunity, T cell proliferation dysfunction, but normal
antibody responses. Both patients’
T cells were missing surface expression of TCRαβ, though CD3+ cells expressed
TCRgd. A homozygous mutation in
the T cell receptor alpha constant [TRAC]
gene was found in both patients.
Both patients were treated successfully with sibling bone marrow
transplants.
WIP deficiency/Wiskott-Aldrich
Syndrome-like phenotype:Wiskott-Aldrich
protein [WASP] binds with WASP-interacting protein [WIP] to form a stable
complex. A Morrocan infant
presented with symptoms suggesting WAS, such as recurrent infections, eczema,
and T cell lymphopenia. Sequencing
demonstrated normal WASP sequence and
expression, though WASP was undetectable in the patient’s cells. Additional analyses determined that WIP
was absent as well and that a homozygous nonsense mutation was present in the WIPF1 gene, coding for WIP. The patient was treated with unrelated
cord blood transplantation at 4½ months and was reported to be thriving at 21
months.
Parvaneh et al. conclude noting that
reports of novel primary immunodeficiencies are increasing. There is no formal
evidence that the incidence of PID has increased; however, improved treatment,
allowing long-term survival may have increased the pool of mutant alleles in
the general population. The growing number of reportsofnew PIDs probably reflects several
factors including:1) the increasing awareness of practicing physicians
regarding the clinical and laboratory manifestations of PID; 2) improved
networking (or collaboration) within the international PID community; 3) new
immunological techniques to analyze leukocyte subsets and function; and finally
4) usage of next generation sequencing (whole exome sequencing) which has had a
major impact on the field. The
authors emphasize the importance of this expansion in knowledge, not only to
improve the patients’ outcomes, but also to contribute to the general
understanding of these immune diseases.
