The Allergic Connection
Type 1 diabetes (T1D) results from an abnormal T-cell-mediated autoimmune response, primarily of the T helper type 1 (Th1) cells. In contrast, T helper type 2 (Th2) cells predominate in allergic diseases, such as atopic dermatitis (AD) and asthma. The increasing incidence of both autoimmune and allergic diseases suggests that there is a positive association between the two in individual patients.
A study examined the association between islet autoantibodies and the development of eczema, allergic rhinitis and asthma by following 2,159 newborns with a first-degree T1D relative and selected HLA genotypes.. The study found:
- Cumulative incidence was 22% for atopic eczema, 9% for allergic rhinitis and 7.5% for asthma.
- The presence of diabetes-related autoantibodies was protective against the development of asthma and eczema.
- The presence of islet cell antibodies protected against development of allergic rhinitis, as did the presence of multiple autoantibodies initially appearing together.
- The relationship with eczema depends on which autoantibody first appears.
Genetic variation in the gene encoding kinesin family member 3A (KIF3A) has been associated with AD, and research has found KIF3A is required for skin barrier homeostasis. Thus, a KIF3A deficiency causes disrupted skin barrier function and promotes AD development.
- KIF3A plays a role in the delivery of MT1-MMP to the cell surface.
- Membrane-bound MT1-MMP is a “master switch” proteinase in a wide range of cell types, important for processes like leukocyte migration during extravasation, inflammation, diabetes and metastasis.
- KIF3A is also found to be crucial for mediating insulin–stimulated GLUT4 translocation and glucose uptake.
Key takeaways: Regulation of KIF3A and other Kinesin-powered delivery is a promising therapy measure and early target for the modulation of MT1-MMP–associated cell invasion in macrophages and other lymphocytes, which play a crucial role in diseases like T1D and AD.
- Cardwell, Chris R., et al. “A Meta-Analysis of the Association Between Childhood Type 1 Diabetes and Atopic Disease.” Diabetes Care, American Diabetes Association, 1 Sept. 2003, care.diabetesjournals.org/content/26/9/2568.
- Diabetologia. “Diabetes-Related Autoantibodies and Atopic Diseases.” PracticeUpdate, www.practiceupdate.com/journalscan/72222/2/8?elsca1=emc_enews_daily-digest.
- Guo, Hui-Ling, et al. “The Axin/TNKS Complex Interacts with KIF3A and Is Required for Insulin-Stimulated GLUT4 Translocation.” Cell Research, Nature Publishing Group, Aug. 2012, www.ncbi.nlm.nih.gov/pmc/articles/PMC3411167/.
- Stevens, Mariana L., et al. “Disease-Associated KIF3A Variants Alter Gene Methylation and Expression Impacting Skin Barrier and Atopic Dermatitis Risk.” Nature News, Nature Publishing Group, 14 Aug. 2020, www.nature.com/articles/s41467-020-17895-x.
- Wiesner, Christiane, et al. “KIF5B And KIF3A/KIF3B Kinesins Drive MT1-MMP Surface Exposure, CD44 Shedding, and Extracellular Matrix Degradation in Primary Macrophages.” Blood, American Society of Hematology, 2 Sept. 2010, ashpublications.org/blood/article/116/9/1559/103860/KIF5B-and-KIF3A-KIF3B-kinesins-drive-MT1-MMP.