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The following is a summary of “Tryptophan–kynurenine metabolites associate with inflammation and immunologic phenotypes in common variable immunodeficiency,” published in the May 2025 issue of Journal of Allergy and Clinical Immunology by Jørgensen et al. 

Chronic T-cell and monocyte/macrophage activation in common variable immunodeficiency (CVID) have been associated with immune pathways like tryptophan–kynurenine, though the cause remains unclear.  

Researchers conducted a retrospective study to examine the tryptophan–kynurenine pathway in CVID and its links to clinical features, immune profiles, and gut microbial dysbiosis.  

They measured serum levels of tryptophan–kynurenine pathway metabolites and neopterin by liquid chromatography–tandem mass spectrometry in a discovery cohort (n = 40), a validation cohort (n = 53), and healthy controls (n = 60), B-cell phenotype analysis was performed in both cohorts. In the discovery cohort, inflammatory markers were assessed using enzyme immunoassay, and levels of lipopolysaccharide (LPS), gut microbial composition, and dietary intake via food frequency questionnaire were evaluated.  

The results showed that individuals with CVID had elevated tryptophan–kynurenine pathway activity compared to healthy controls, demonstrated by higher kynurenine/tryptophan ratio (KT ratio), 3-hydroxykynurenine, and quinolinic acid levels in both the discovery and validation cohorts. These changes were most evident in those with autoimmune or inflammatory features but were also seen to a lesser extent in those with infections only. In CVID, these metabolites were linked to soluble (S) monocyte activation markers (sCD14, sCD163, neopterin), T-cell activation markers (sCD25), and B-cell subsets (e.g., naïve B cells). Specific gut microbial taxa appeared to affect tryptophan–kynurenine metabolism, while LPS and dietary intake showed no such association.  

Investigators concluded that altered levels of several metabolites in the tryptophan-kynurenine pathway were identified in 2 distinct CVID cohorts and were associated with systemic inflammation and B-cell phenotype. 

Source: jacionline.org/article/S0091-6749(25)00515-9/fulltext