Serum IL-31 levels were significantly higher in dogs with CAD than in healthy dogs (Fig 1A). The mean (SE) IL-31 concentration was 165.76 (SE: 9.42) in healthy dogs and 237.86 (SE: 14.55) in CAD-affected dogs, which was statistically significant (p = 0.001) as presented in Table 1. Increased serum IL-31 levels in CAD-affected dogs indicated active pruritogenic signalling during disease progression. This finding was consistent with previous reports showing that administration of canine IL-31 directly induced pruritic behaviour in dogs
(Gonzales et al., 2013). Similar evidence demonstrated a positive association between IL-31 levels and disease severity during active flares
(Marsella et al., 2017). The elevated IL-31 observed in the present study may be attributed to increased production by TH2 cells and its action on sensory nerve fibres through the IL-31 receptor complex, ultimately triggering the itch sensation
(Furue et al., 2018). A previous study failed to detect IL-31 mRNA in the skin of dogs with AD
(Mizuno et al., 2009). Therefore, serum IL-31 estimation may be more informative than IL-31 mRNA expression analysis. Long-term caninized anti-IL-31 monoclonal antibody therapy was evaluated in a beagle with severe atopic dermatitis. This was the first clinical study of its kind reported from India. The antibody binds to and neutralizes IL-31. Treatment reduced pruritus, erythema and lesion severity
(Sundararajan et al., 2026). The marked reduction in pruritus after IL-31 neutralization justifies the role of serum IL-31 as an important itch-inducing cytokine in dogs.
Serum total IgE levels were markedly increased in CAD-affected dogs compared with healthy controls, as illustrated in Fig 1B. The mean (SE) IgE concentration was 6.86 (SE: 0.20) in healthy dogs and 8.06 (SE: 0.27) in CAD-affected dogs. The findings presented in Table 1 showed that serum IgE concentrations were significantly increased in CAD dogs compared with controls (p = 0.010). Higher serum IgE levels in CAD-affected dogs reflected IgE-mediated hypersensitivity reactions. Previous findings also reported significantly increased serum IgE concentrations in clinically affected Pugs that were positive on intradermal testing compared with healthy and test-negative dogs, emphasizing the association between elevated IgE levels and true allergic sensitization
(Bhagya et al., 2023). Damage to the skin barrier allows allergens to penetrate the skin more easily (van den
Bogaard et al., 2023). This activates TH2 immune responses through antigen-presenting cells. Consequently, IgE production increases
(Facheris et al., 2023; Wollenberg et al., 2021). Elevated IgE contributes to hypersensitivity reactions (
Santoro, 2019;
Wüthrich, 1978). Increased IgE levels are reported in both serum and skin of affected patients (
Wüthrich, 1978). Therefore, IgE plays an important role in the development of atopic dermatitis (AD).
@figue1
Clinical severity assessment revealed a mean CADESI-04 score of 64.25 (SE: 1.37; median: 62.5; range: 60-75) and a mean pVAS score of 8.16 (SE: 0.06; median: 8.15; range: 7.8-8.5) in CAD-affected dogs. Correlation analysis showed that serum IL-31 levels were strongly and positively related to pVAS scores (r = 0.804; p = 0.003) (Table 2 and Fig 2B). This means that dogs with higher IL-31 levels tended to have more severe itching. However, serum IL-31 levels were not significantly related to CADESI-04 scores (r = 0.327; p = 0.297) (Table 2 and Fig 2A). Serum total IgE levels showed a positive relationship with both CADESI-04 scores (r = 0.320; p = 0.308) and pVAS scores (r = 0.460; p = 0.132) (Table 2). However, these relationships were not statistically significant (Fig 2C and 2D). The strong positive correlation between IL-31 and pVAS scores indicated that higher IL-31 concentrations were closely associated with increased pruritus intensity. This observation was in agreement with earlier findings reporting significantly elevated IL-31 concentrations in atopic dogs and a significant positive correlation between IL-31 and pVAS scores. These findings further support the association between IL-31 and pruritic activity
(Chaudhary et al., 2019). A significant positive correlation between serum IL-31 levels and disease severity during active flares was also reported in an experimental CAD model, suggesting IL-31 as a potential biomarker for pruritic activity and therapeutic response
(Marsella et al., 2017). In contrast, total IgE showed weak and non-significant correlations with both CADESI-04 and pVAS, suggesting that circulating IgE levels were not directly associated with clinical severity of skin lesions or pruritus in the present study. This finding differed from previous observations that reported a significant positive correlation between IgE concentrations and CADESI scores
(Lo et al., 2012). The lack of significant correlation between IgE and clinical indices in the present study indicates that IgE may reflect atopic status rather than the current severity of lesions or pruritus. One study reported that treatments such as selective Janus kinase inhibitor and corticosteroid improve clinical manifestations without significant changes in serum IgE levels
(Aleo et al., 2023). Yet, there appear to be no reports on effect of caninized anti-IL-31 monoclonal antibodies on IgE level to compare the observations of the present findings. Therefore, serum IgE may have greater diagnostic value in CAD than its role in monitoring disease severity or treatment response. Furthermore, the small number of atopic dogs included in this study is an important limitation. Therefore, future studies with a larger number of dogs with naturally occurring CAD are needed to confirm these findings and better understand the relationship between serum IL-31and total IgE with disease severity and response to treatment in dogs with CAD.