Keeping it in the family: the case for considering late-onset combined immunodeficiency a subset of common variable immunodeficiency disorders

ABSTRACT

Introduction: Common variable immunodeficiency disorders (CVID) are the most frequent symptomatic primary immune defect in adults. Within the broad spectrum of CVID, a proportion of patients present with a predominant T cell phenotype associated with increased mortality. These patients are termed late-onset combined immunodeficiency (LOCID) and are currently separated from patients suffering from CVID.

Areas covered: We have recently codiscovered a new CVID-like disorder caused by mutations of the NFKB1 gene. Members of this non-consanguineous New Zealand kindred have a very diverse spectrum of phenotypes in spite of carrying the identical mutation. The proband appears to have the autoimmune variant. The proband’s recently deceased sister best matched LOCID while other family members are less severely affected, including one asymptomatic adult brother, who has an affected daughter. Differences in genetics was one of the main arguments for separating these disorders in the past.

Expert commentary: Given the recent advances in the understanding of the genetic basis of these conditions, we present the case that LOCID should now be considered a subset of CVID, rather than a separate disorder. At a clinical level, this distinction is less important but it is imperative these patients are carefully evaluated, the relevant complications are treated, and they are offered prognostic information.

KEYWORDS:

• CVID
• LOCID
• IVIG
• NFKB1
• CVID-like

Acknowledgments

We thank the family for participating in our studies for the benefit of others. Sadly, the proband’s sister recently passed away. We appreciated her support for our research. We dedicate this article to her memory. May she rest in peace. We thank the A+ Trust, AMRF, IDFNZ and ASCIA for grant support for our CVID research.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper is not funded.