P0459 Plasma IgA as a biomarker and IL-21 as a potential therapeutic target in Inflammatory Bowel Disease
Authors: Tsai T , Hsu J L 
Published: January 2025

Abstract

Background
B cells and their secreted immunoglobulin A (IgA) play an increasingly recognised role in Inflammatory Bowel Disease (IBD) therapy. While plasma IgA levels have been shown to be elevated in IBD patients compared to healthy controls and decrease with biologic therapy1, its relationship with clinical parameters and therapeutic outcomes remains unclear. Cytokines such as interleukin-21 (IL-21), interleukin-6 (IL-6), and B-cell activating factor (BAFF) are known to regulate B-cell activity in IBD2, but their role in IgA secretion requires further investigation. This study aimed to explore these relationships and identify key cytokines regulating IgA secretion.

Methods
We enrolled 43 patients with IBD (31 ulcerative colitis (UC) and 12 with Crohn’s disease (CD)) between 2022 to 2024. Plasma levels of IgA, haemoglobin (Hb), haematocrit (HCT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin, calcium, and ferritin were measured at baseline for all patients and at week 14 for patients receiving biological therapy (adalimumab or vedolizumab, n=16). Clinical response was defined as a Crohn’s Disease Activity Index (CDAI) &lt;150 for CD patients or a ≥2-point reduction in the partial Mayo score for UC patients. Statistical analysis was performed using the Student’s t-test and linear regression. Additionally, the DAKIKI cell line was used to assess which cytokines influence IgA secretion.

Results
Plasma IgA levels significantly decreased at week 14 in most patients receiving biologic therapy (P = 0.0022) (Figure 1A), irrespective of clinical response. However, patients who did not achieve clinical response had significantly higher baseline IgA levels compared to those who did achieve (3057±217.2 vs 1880±214.1 μg/mL, P = 0.0032) (Figure 1B). In all patients, plasma IgA levels showed positive correlations with HCT and ESR, and a negative correlation with ferritin level. Notably, these correlations were stronger in CD patients, where IgA levels showed more significant associations with Hb (R² = 0.2754, P = 0.0369), ESR (R² = 0.3938, P = 0.0123), CRP (R² = 0.3003, P = 0.028), and CDAI (R² = 0.5739, P = 0.0017). In vitro, IL-21 and IL-6 both stimulated IgA secretion in DAKIKI cells, with IL-21 demonstrating greater potency (Figure 2).

Conclusion
Plasma IgA levels are correlated with disease activity and clinical parameters, particularly in patients with CD, and may serve as a useful biomarker for monitoring therapeutic response. Baseline IgA levels may predictive clinical response at week 14. Additionally, IL-21 appears to be a key cytokine driving IgA secretion, suggesting its potential as a therapeutic target in IBD management.

References
1.Lee B, Hsu J, Tsai T. Correlation between plasma IgA level and biological therapy in inflammatory bowel disease. J Can Assoc Gastroenterol. 2024;194(7):241. doi:10.1093/jcag/gwad061.241
2.Rodriguez-Lago I, Marigorta UM, Barreiro-de Acosta M. Preclinical inflammatory bowel disease: back to the future. Gastroenterology. 2021;160(1):475-476. doi:10.1053/j.gastro.2020.04.081