Interleukin-9 and apolipoprotein A-IV could serve as new biomarkers for predicting the severity of urticaria, according to the results of a recent observational study.

Chronic spontaneous urticaria (CSU) is a condition characterized by the presence of wheals, with or without angioedema, that occur daily or almost daily for more than 6 weeks. Previous studies have shown higher levels of complement fraction 5a (C5a) in the serum of patients with chronic urticaria. However, the role of C5a as a biomarker for predicting disease severity and resistance to antihistamines is not well understood. 

Interleukin-9 (IL-9) has been found to play a crucial role in various atopic disorders, autoimmune inflammation, and antitumor immunity in mouse models. Some authors have suggested that CSU patients may have a higher expression of IL-9 in their peripheral blood due to significantly elevated levels of Th9 cells. It has also been recommended that apolipoprotein A-IV (apo A-IV), an anti-inflammatory molecule involved in lipid transport and antiatherogenic pathways, may have a role in allergic disorders. 

This prospective observational study, published in the journal Asia Pacific Allergy, assesses the role of IL-9, C5a, and apo A-IV as biomarkers for disease severity and response to antihistamines in CSU patients.

Baseline Characteristics

The study included 95 patients with CSU and 42 controls. CSU patients were monitored on days 15, 30, 60, and 90. Forty-two controls, matched for age and gender, were included in the study. The mean age (SD) was 33.77 (8.07) years among CSU patients and 35.50 (7.68) years (P = 0.207) for controls. There was no significant difference in the male-to-female ratio between cases and controls (P = 0.88). Table 1 summarises the clinical and epidemiological characteristics of patients with CSU.

C5a Levels Significantly Higher in CSU Patients

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C5a levels were significantly higher in CSU patients compared to healthy individuals (P = 0.004). There was no statistically significant difference in IL-9 levels between CSU patients and controls (P = 0.082). Apo A-IV levels did not show a significant difference between CSU cases and controls (P = 0.173).

Disease Severity and Serological Marker Levels

A slight positive correlation was observed between initial disease severity and C5a levels, although it was not statistically significant. There were minor positive associations between IL-9 levels and baseline disease severity, as well as between apo A-IV levels and baseline disease severity.

Antihistamine Response and Serological Marker Levels

There were no statistically significant differences in the levels of C5a and apo A-IV (P = 0.460) between individuals who responded to antihistamines and those who did not. However, antihistamine responders exhibited significantly higher levels of IL-9 compared to nonresponders (P = 0.008).

ROC Curve Analysis Highlighted C5a’s Superior Diagnostic Accuracy

ROC curve analysis indicated that C5a exhibited the highest diagnostic accuracy compared to IL-9 and apo A-IV levels. Moreover, 63.1% of the 95 individuals exhibited increased serum IgE levels. Nonresponders had significantly elevated serum IgE levels compared to responders (P = 0.031). There was no significant association between baseline illness severity and serum IgE levels (ρ = 0.07, P = 0.549), or with anti-TPO antibody levels (ρ = −0.14, P = 0.203). Twelve patients (12.6%) had elevated anti-TPO antibody levels, which were substantially greater in nonresponders than in responders (P = 0.039).

Source:

Bhatia, D., Mehta, H., Bishnoi, A., Srivastava, N., Vinay, K., Parsad, D., & Kumaran, M. S. (2024). A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria. Asia Pacific Allergy. https://doi.org/10.5415/apallergy.0000000000000132 

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