Serologic IL-18 increase with B-cell IL-18R loss characterizes selective IgA deficiency

Area of Science:

• Immunology
• Genetics

Background:

• Selective IgA deficiency (sIgAD) is the most common primary antibody deficiency.
• It is associated with increased risks of respiratory infections, atopy, and autoimmunity.
• The underlying serologic and B-cell pathways are poorly understood.

Purpose of the Study:

• To characterize a population-based adult sIgAD cohort.
• To identify soluble and transcriptional signatures linking cytokine milieu to B-cell dysfunction.

Main Methods:

• Studied 61 adults with sIgAD and 73 controls.
• Measured serum immunoglobulins, autoantibodies, and a 65-plex cytokine panel.
• Performed bulk RNA-seq on purified B cells.

Main Results:

• sIgAD adults exhibited airway infections, atopy, and ANA/ENA positivity.
• A five-analyte signature (IL-18, sCD40L, TSLP, CCL3, TWEAK) was elevated in sIgAD.
• Reduced IL-18 receptor component expression was found in sIgAD B cells.

Conclusions:

• Adult sIgAD has a blood-measurable endotype with an IL-18-centered signature.
• Reduced IL-18 receptor expression and altered B-cell signaling are key features.
• The IL-18-IL-18R axis is a potential target for sIgAD biomarkers and therapies.