Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jun 12:12:1386959.
doi: 10.3389/fped.2024.1386959. eCollection 2024.

Monogenic Inborn Errors of Immunity with impaired IgG response to polysaccharide antigens but normal IgG levels and normal IgG response to protein antigens

Maria Fasshauer  1 , Sarah Dinges  2 , Olga Staudacher  2 , Mirjam Völler  2 , Anna Stittrich  3 , Horst von Bernuth  2   4   5   6 , Volker Wahn #  2 , Renate Krüger #  2
Affiliations
Review

Monogenic Inborn Errors of Immunity with impaired IgG response to polysaccharide antigens but normal IgG levels and normal IgG response to protein antigens

Maria Fasshauer et al. Front Pediatr. .

Abstract

In patients with severe and recurrent infections, minimal diagnostic workup to test for Inborn Errors of Immunity (IEI) includes a full blood count, IgG, IgA and IgM. Vaccine antibodies against tetanus toxoid are also frequently measured, whereas testing for anti-polysaccharide IgG antibodies and IgG subclasses is not routinely performed by primary care physicians. This basic approach may cause a significant delay in diagnosing monogenic IEI that can present with an impaired IgG response to polysaccharide antigens with or without IgG subclass deficiency at an early stage. Our article reviews genetically defined IEI, that may initially present with an impaired IgG response to polysaccharide antigens, but normal or only slightly decreased IgG levels and normal responses to protein or conjugate vaccine antigens. We summarize clinical, genetic, and immunological findings characteristic for these IEI. This review may help clinicians to identify patients that require extended immunologic and genetic evaluations despite unremarkable basic immunologic findings. We recommend the inclusion of anti-polysaccharide IgG antibodies as part of the initial routine work-up for possible IEI.

Keywords: IEI; pneumococcal infections; polysaccharide; primary immunodeficiency; vaccination; vaccines.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Humoral immune response to polysaccharides. Modified from Pollard et al. (17).
Figure 2
Figure 2
Humoral immune response to conjugated polysaccharides. Modified from Pollard et al. (17). PS, polysaccharide.
See this image and copyright information in PMC

References

    1. Bousfiha A, Jeddane L, Picard C, Al-Herz W, Ailal F, Chatila T, et al. Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification. J Clin Immunol. (2020) 40(1):66–81. 10.1007/s10875-020-00758-x - DOI - PMC - PubMed
    1. Pieniawska-Śmiech K, Pasternak G, Lewandowicz-Uszyńska A, Jutel M. Diagnostic challenges in patients with inborn errors of immunity with different manifestations of immune dysregulation. J Clin Med. (2022) 11(14):4220. 10.3390/jcm11144220 - DOI - PMC - PubMed
    1. Farmand S, Baumann U, von Bernuth H, Borte M, Foerster-Waldl E, Franke K, et al. Interdisciplinary AWMF guideline for the diagnostics of primary immunodeficiency. Klin Padiatr. (2011) 223(6):378–85. 10.1055/s-0031-1287835 - DOI - PubMed
    1. Knight V, Heimall JR, Chong H, Nandiwada SL, Chen K, Lawrence MG, et al. A toolkit and framework for optimal laboratory evaluation of individuals with suspected primary immunodeficiency. J Allergy Clin Immunol Pract. (2021) 9(9):3293–307.e6. 10.1016/j.jaip.2021.05.004 - DOI - PubMed
    1. Umetsu DT, Ambrosino DM, Quinti I, Siber GR, Geha RS. Recurrent sinopulmonary infection and impaired antibody response to bacterial capsular polysaccharide antigen in children with selective IgG-subclass deficiency. N Engl J Med. (1985) 313(20):1247–51. 10.1056/NEJM198511143132002 - DOI - PubMed