ORIGINAL RESEARCH article
Front. Immunol.
Sec. Primary Immunodeficiencies
Serologic IL-18 increase with B-cell IL-18R loss characterizes selective IgA deficiency
Provisionally accepted
Andri Leo Lemarquis1*
Hildur Sigurgrímsdóttir2
Fannar Theódórs2
Gudmundur Jorgensen2Ida Karnsund2
Olov Ekwall3Ingileif Jonsdóttir2
Björn Ludviksson2- 1City of Hope National Medical Center, Duarte, United States
- 2Haskoli Islands, Reykjavík, Iceland
- 3Goteborgs universitet, Gothenburg, Sweden
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Selective IgA deficiency (sIgAD) is the most common primary antibody deficiency in the western world. While affected individuals are known to have a higher prevalence of autoimmunity, atopy and infectious diseases the molecular mechanisms immune dysregulation in sIgAD remains unknown. Clinical phenotyping of 61 adult individuals with sIgAD in Iceland was done in sIgAD individuals, revealing significantly higher prevalence of various atopic, autoimmune or infectious complications compared to healthy matched controls. Detailed peripheral blood immunological phenotyping and cytokines and autoantibodies analysis compared to matched adult healthy individuals revealed high positivity for antinuclear autoantibody titers and higher titers of IL-18 in addition to the germinal center related factors; CCL3, sCD40L, TSLP and TWEAK. To assess the B cell mediated drivers of these changes we performed RNA sequencing on isolated CD19+ B cells from sIgAD individuals was performed before and after stimulation with CpG (TLR-9) revealing altered transcriptional signatures related to the IL18 superfamily in B cells in IgA deficiency. Altogether we confirm that sIgAD is strongly linked to B-cell dysregulation and affected individuals have raised serum IL-18 and lower IL-18R expression in B cells. Altogether our findings indicate that IL-18/IL-18R activation may act as a biomarker in ANA-positive sIgAD.
Keywords: IgA, Primary antibody deficiencies, IL18, TSLP, CpG, TWEAK, sCD40L, CCL3
Received: 18 Aug 2025; Accepted: 19 Nov 2025.
Copyright: © 2025 Lemarquis, Sigurgrímsdóttir, Theódórs, Jorgensen, Karnsund, Ekwall, Jonsdóttir and Ludviksson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Andri Leo Lemarquis, andrileolemarquis@gmail.com
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