D3.01 - Association between allergen-related antibodies and clinical phenotypes of IgG4-related disease (IgG4-RD)

IgG4-RD patients with allergic diseases have more organ involvement. Allergens are key triggers of allergic diseases. Thus, it is necessary to further explore the association between allergen-related antibodies and IgG4-RD.

A total of 208 IgG4-RD patients were recruited. Plasma specific IgE (sIgE), and specific IgG4 (sIgG4) were collected. K-Modes clustering was used to construct IgG4-RD organ phenotypes. Factor analysis was used to extract common factors reflecting the characteristics of allergen-related antibodies in IgG4-RD patients. Multivariate Logistic regression was used to analyze the association between each factor and different organ phenotypes after adjusting for age and gender.

Three organ phenotypes were constructed based on organ involvement in IgG4-RD. Cluster 1 was characterised by involvement of the lacrimal glands (95.7%), paranasal sinuses (75.7%), and submandibular glands (70%). Cluster 2 was characterised by involvement without significant glandular. Cluster 3 was characterised by involvement of the lymph nodes (73.3%), submandibular glands (73.1%), pancreas (66.7%), and lacrimal glands (61.7%).It was found that patients in Cluster 2 had no significant glandular organ involvement, and these patients often had a shorter disease course, lower IgG4 levels, and lower RI. SIgG4 and sIgE/sIgG4 against dust mites and their components were found to be correlated with IgG4 as well as RI. After adjusting for age and gender, compared with phenotype 2 (no significant exocrine gland involvement), higher levels of factor 6  (characterized by high proportions of sIgG4 and sIgE against Der p 5 and Der p 21) (OR=906.7, 95% CI 10.19-80680.4, P=0.003) and RI (OR=1.49, 95% CI 1.11-2, p=0.008), and lower level of factor 8 (characterized by high proportions of f1, f2, and f4 sIgE)  (OR=0.16, 95% CI 0.04-0.71, p=0.016) were associated with increased risk of organ involvement in phenotype 1 (exocrine gland involvement). Factor 6 was mainly composed of sIgE and sIgG4 of dust mite components Der p 5 and Der p 21, while factor 8 had a higher proportion of sIgE of f1 and f4.

This is the first study to find an association between allergen-related antibodies and clinical phenotypes of IgG4-RD. In particular, antibodies related to dust mites and their components are closely associated with disease activity and exocrine gland involvement. sIgE of f1 and f4 is associated with the non-gland involvement phenotype, suggesting that allergen exposure may be closely related to clinical phenotypes.