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. 2025 May 14:16:1536128.
doi: 10.3389/fimmu.2025.1536128. eCollection 2025.

Th2 predominance and decreased NK cells in patients with hereditary angioedema

Linda Sundler Björkman  1 , Evelina Elmér  2   3 , Arne Egesten  1 , Lillemor Skattum  3   4
Affiliations

Th2 predominance and decreased NK cells in patients with hereditary angioedema

Linda Sundler Björkman et al. Front Immunol. .

Abstract

Background: In this study we included patients with hereditary angioedema (HAE) caused by decreased levels of C1 inhibitor (HAE-C1INH). An increased risk of autoimmune disorders, particularly systemic lupus erythematosus (SLE), has been reported in HAE-C1INH. This suggests that complement consumption affects adaptive immunity.

Objective: To investigate lymphocyte subpopulations in relation to disease activity and complement activation in HAE-C1INH patients and matched controls.

Methods: Flow cytometry of peripheral blood lymphocyte populations, measurements of complement and complement fragments, and collection of clinical data.

Results: NK cell counts were lower in HAE-C1INH patients, and their frequencies were related to disease activity. The T helper (Th) cell balance was skewed towards more Th2 cells and less Th1 cells in HAE-C1INH patients compared to controls. There were also lower frequencies of class-switched B cells and plasmablasts in patients. Levels of C4 and the complement activation fragment C3d were related to disease activity.

Conclusions: Blood lymphocyte populations are altered in HAE-C1INH, a finding which may be of pathophysiological importance considering the increased risks of both autoimmunity and allergy associated with HAE-C1INH.

Keywords: NK cells; T helper 2 cells; adaptive immunity; complement activation; hereditary angioedema.

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Conflict of interest statement

LSB has received an unrestricted grant from CSL Behring and is a member of the Swedish advisory board for CSL Behring. LSB and AE have received honoraria from BioCryst, Takeda and CSL Behring. The remaining 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.

Figures

Figure 1
Figure 1
Serum C4 concentrations in HAE-C1INH patients with high disease activity (HAEhigh, defined as ≥ 2 angioedema attacks per month) and low disease activity (HAElow, defined as < 2 angioedema attacks per month), respectively. The Mann-Whitney U test was applied for group comparisons.
Figure 2
Figure 2
EDTA plasma C3d concentrations in HAE-C1INH patients with high (HAEhigh, defined as ≥2 angioedema attacks per month) and low disease activity (HAElow, defined as <2 angioedema attacks per month), respectively. The Mann-Whitney U test was applied for group comparisons.
Figure 3
Figure 3
NK cell concentrations in HAE-C1INH patients and matched controls. The Mann-Whitney U test was applied for group comparisons.
Figure 4
Figure 4
Proportions of NK cells in HAE-C1INH patients with high (HAEhigh, defined as ≥2 angioedema attacks per month) and low disease activity (HAElow, defined as <2 angioedema attacks per month), respectively. The Mann-Whitney U test was applied for group comparisons.
Figure 5
Figure 5
Proportions of Th2 of effector memory T helper cells in HAE-C1INH patients and matched controls. The Mann-Whitney U test was applied for group comparisons.
Figure 6
Figure 6
Proportions of Th1 of central memory T helper cells in HAE-C1INH patients and matched controls. The Mann-Whitney U test was applied for group comparisons.
Figure 7
Figure 7
Correlation between C4d/C4 ratio and Th2 effector memory T helper cells in HAE-C1INH patients. The correlation was determined using the Spearman rank correlation test.
Figure 8
Figure 8
Proportions of plasmablasts of B cells in HAE-C1INH patients and matched controls. The Mann-Whitney U test was applied for group comparisons.
Figure 9
Figure 9
Concentrations of plasmablasts in HAE-C1INH patients and matched controls. The Mann-Whitney U test was applied for group comparisons.
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References

    1. Busse PJ, Christiansen SC. Hereditary angioedema. N Engl J Med. (2020) 382:1136–48. doi: 10.1056/NEJMra1808012 - DOI - PubMed
    1. Brickman CM, Tsokos GC, Balow JE, Lawley TJ, Santaella M, Hammer CH, et al. . Immunoregulatory disorders associated with hereditary angioedema. I. Clinical manifestations of autoimmune disease. J Allergy Clin Immunol. (1986) 77:749–57. doi: 10.1016/0091-6749(86)90424-0 - DOI - PubMed
    1. Sundler Björkman L, Persson B, Aronsson D, Skattum L, Nordenfelt P, Egesten A. Comorbidities in hereditary angioedema-A population-based cohort study. Clin Transl Allergy. (2022) 12:e12135. doi: 10.1002/clt2.12135 - DOI - PMC - PubMed
    1. Khan S, Tarzi MD, Doré PC, Sewell WA, Longhurst HJ. Secondary systemic lupus erythematosus: an analysis of 4 cases of uncontrolled hereditary angioedema. Clin Immunol. (2007) 123:14–7. doi: 10.1016/j.clim.2006.09.015 - DOI - PubMed
    1. Triggianese P, Chimenti MS, Toubi E, Ballanti E, Guarino MD, Perricone C, et al. . The autoimmune side of hereditary angioedema: insights on the pathogenesis. Autoimmun Rev. (2015) 14:665–9. doi: 10.1016/j.autrev.2015.03.006 - DOI - PubMed

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