Intestinal Candida albicans overgrowth in IgA deficiency

Moreno-Sabater A, Sterlin D, Imamovic L et al.  J Allergy Clin Immunol. 2023 May 9:S0091-6749(23)00566-3. doi: 10.1016/j.jaci.2023.03.033. 

Background

Secretory IgA interacts with commensal bacteria, but its impact on human mycobiota ecology has not been widely explored. In particular, whether human IgA-deficiency is associated with gut fungal dysbiosis remains unknown.

Objectives

Our goal was to study the impact of IgA on gut mycobiota ecology.

Methods

The Fungi-Flow method was used to characterize fecal, systemic, and maternal IgA, IgM, and IgG responses against 14 representative fungal strains (yeast/spores or hyphae forms) in healthy donors (HDs) (n = 34, 31, and 20, respectively) and to also compare gut mycobiota opsonization by secretory antibodies in HDs (n = 28) and patients with selective IgA deficiency (SIgAd) (n = 12).

Stool mycobiota composition was determined by internal transcribed spacer gene sequencing in HDs (n = 23) and patients with SIgAd (n = 17). Circulating CD4+ T-cell cytokine secretion profiles were determined by intracellular staining. The impact of secretory IgA, purified from breast milk (n = 9), on Candida albicans growth and intestinal Caco-2 cell invasion was tested in vitro.

Results

Homeostatic IgA binds commensal fungi with a body fluid–selective pattern of recognition. In patients with SIgAd, fungal gut ecology is preserved by compensatory IgM binding to commensal fungi. Gut C albicans overgrowth nevertheless occurs in this condition but only in clinically symptomatic patients with decreased TH17/TH22 T-cell responses. Indeed, secretory IgA can reduce in vitro budding and invasion of intestinal cells by C albicans and therefore exert control on this pathobiont.

Conclusion

IgA has a selective impact on C albicans ecology to preserve fungal-host mutualism.

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