The long and winding road to IgA deficiency: causes and consequences

ABSTRACT

Introduction: The most common humoral immunodeficiency is IgA deficiency. One of the first papers addressing the cellular and molecular mechanisms underlying IgA deficiency indicated that immature IgA-positive B-lymphocytes are present in these patients. This suggests that the genetic background for IgA is still intact and that class switching can take place. At this moment, it cannot be ruled out that genetic as well as environmental factors are involved.

Areas covered: A clinical presentation, the biological functions of IgA, and the management of IgA deficiency are reviewed. In some IgA deficient patients, a relationship with a loss-of-function mutation in the TACI (transmembrane activator and calcium-modulating cyclophilin ligand interaction) gene has been found. Many other genes also have been associated. Gut microbiota are an important environmental trigger for IgA synthesis.

Expert commentary: Expression of IgA deficiency is due to both genetic and environmental factors and a role for gut microbiota cannot be excluded.

KEYWORDS:

• APRIL
• BAFF
• family case
• IgA
• immune deficiency
• TACI

Acknowledgments

We thank Drs Diana van Kessel and Heleen van Velzen-Blad, St. Antonius Hospital, Nieuwegein, for allowing us to use the data of the family with IgA deficiency presented in Figure 1 and the IgA deficient patients who recovered (Table 1).

Ethics

Approval for including the patient data in this review was obtained from the Medical Ethical Research Committee of the Sint-Antonius Hospital, Nieuwegein, The Netherlands (dossier nr. W16.045).

Declaration of interest

The corresponding author had full access to the data and final responsibility for the submission of the publication. 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

The University College Roosevelt covered all costs associated with the development and the publishing of the present manuscript.