ANP32B and Common Variable Immunodeficiency

This summary evaluates the association between ANP32B (HGNC:16677) and common variable immunodeficiency (MONDO_0015517). The evidence is primarily derived from candidate gene investigations in both single‐patient case reports and multi-patient familial studies. In one case report, patients with CVID were evaluated for mutations in several genes including ANP32B, although no clear pathogenic variant in ANP32B was identified (PMID:22286841). Similarly, a multi-patient study screening functional candidate genes in familial CVID cases also included ANP32B in the analysis but failed to demonstrate disease-causing mutations (PMID:18254984). These findings suggest that while ANP32B was considered a plausible candidate, genetic evidence directly linking it to CVID remains inconclusive.

The genetic evidence in these studies is limited by the absence of definitive pathogenic variants or robust segregation data. Although the candidate gene approach targeted multiple genes within CVID cohorts, no ANP32B variant has been classically assigned to the immunodeficiency phenotype. Furthermore, there were no additional affected relatives or extended pedigrees reported that could substantiate a segregating pattern for ANP32B. As such, the overall genetic support for an association with CVID is modest, falling below thresholds typically required for robust clinical validity.

Functional studies of ANP32B have largely focused on its role in cell proliferation, apoptosis, and viral replication rather than on immune function. For instance, several investigations have examined ANP32B in the context of cancer biology and influenza virus replication, with experiments often utilizing knockout or overexpression models. These studies, while informative regarding the protein’s broader cellular roles, do not align directly with the immunological dysfunction observed in CVID. No functional assay specifically addressing the impact of ANP32B dysfunction on B cell development or immunoglobulin production in CVID patients has been reported. Therefore, the experimental evidence does not currently provide mechanistic support for a role in CVID pathogenesis.

It is also noteworthy that the candidate gene studies were comprehensive in evaluating multiple genetic loci underlying CVID. However, the lack of recurrent or founder variants in ANP32B undermines the argument for its direct involvement in disease causation. The absence of consistent genetic hits—despite analyzing several unrelated probands (PMID:22286841 and PMID:18254984)—further reinforces a limited role for ANP32B. This contrasts with other genes in which pathogenic mutations have been more clearly delineated in recessive inheritance models.

Integration of the available genetic and functional evidence suggests that ANP32B’s contribution to CVID, if any, is marginal at present. The candidate gene studies have not yielded definitive variants or segregation evidence to support a robust association. Additionally, while ANP32B is biologically active in other cellular processes, the relevance of these functions to immunodeficiency has not been adequately established by experimental models. In summary, the totality of the data supports only a limited genetic association, indicating that more focused research is needed to determine any potential role in CVID pathogenesis.

Key Take‑home: Although ANP32B remains an interesting candidate based on its cellular functions, current evidence supports only a limited association with common variable immunodeficiency, and further investigation is required before its application in diagnostic decision‑making or clinical settings.

References

• International archives of allergy and immunology • 2012 • Multiorgan infiltration by CD8+ T cells and 1p;16p translocation in a patient with hypogammaglobulinemia and a reduced number of B cells PMID:22286841
• BMC immunology • 2008 • Screening of functional and positional candidate genes in families with common variable immunodeficiency PMID:18254984

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