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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Healthy Processed Foods Research » Research » Publications at this Location » Publication #353489

Research Project: Defining, Measuring, and Mitigating Attributes that Adversely Impact the Quality and Marketability of Foods

Location: Healthy Processed Foods Research

Title: Walnut antigens can trigger autoantibody development in patients with pemphigus vulgaris through a "hit-and-run" mechanism

item LIN, LAN - University Of North Carolina
item MORAN, TIMOTHY - University Of North Carolina
item PENG, BIN - University Of North Carolina
item YANG, JINSHENG - University Of North Carolina
item CULTON, DONNA - University Of North Carolina
item CHE, HUILIAN - China Agricultural University
item JIANG, SONGSONG - China Agricultural University
item LIU, ZHI - University Of North Carolina
item GENG, SONGMEI - Jiaotong University
item Zhang, Yuzhu
item DIAZ, LUIS - University Of North Carolina
item YE, QIAN - University Of North Carolina

Submitted to: Journal of Allergy Clinical Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/26/2019
Publication Date: 5/6/2019
Citation: Lin, L., Moran, T., Peng, B., Yang, J., Culton, D., Che, H., Jiang, S., Liu, Z., Geng, S., Zhang, Y., Diaz, L., Ye, Q. 2019. Walnut antigens can trigger autoantibody development in patients with pemphigus vulgaris through a "hit-and-run" mechanism. Journal of Allergy Clinical Immunology. 144(3):720-728.

Interpretive Summary: The rapid increase in the prevalence of food allergies and food safety concerns of consumers in general have raised awareness of food allergies in recent years. However, the underlying mechanisms of food allergy are still unclear as are the reasons why some food proteins incite exaggerated immune responses. It is known that the seemingly unrelated allergy and autoimmunity may have common aspects in their developments. Recent investigation has demonstrated an association between allergic and autoimmune diseases because of intrinsic dysfunction of the immune system. The present study demonstrated that walnut allergen Jug r 2 and other environmental antigens could be related to the triggers of the autoantibody development in pemphigus vulgaris. Information obtained may facilitate further investigations of the allergenicity of food proteins and the immunological mechanisms of autoimmune diseases and food allergy.

Technical Abstract: While environmental factors are critical for the development of autoimmunity, the inciting agents that trigger autoantibody formation remain elusive. We previously reported that autoantibodies in subjects with endemic pemphigus foliaceus likely arise from immune responses against a cross-reactive sand fly antigen. Here, we have investigated the potential role of environmental antigens in triggering autoantibody development in patients with a non-endemic autoimmune skin disease, pemphigus vulgaris (PV). The specificity of the germline form monoclonal antibodies (mAbs) (germline PV mAbs) of eight anti-desmoglein 3 (Dsg3) pathogenic PV mAbs generated by four groups of investigators were tested for reactivity against several sets of environmental antigens, including insects, pollens, epithelia, fungi and food antigens. We found that all the germline PV mAbs were reactive with antigens from walnut extracts. Further studies revealed that the germline PV mAbs recognized a well-known allergen, Jug r 2, and an uncharacterized 85 kD methyltransferase like protein from walnut. This suggests that walnut antigens may be an inciting environmental agent that activates naïve B cells in genetically predisposed individuals. However, PV patients have much lower levels of Abs against walnut antigens than those of anti-Dsg3 autoantibodies, suggesting that the autoreactive B cells are selected by the Dsg3 autoantigen, and that walnut antigens may not be present by the time of overt PV onset. This may explain the elusiveness of environmental triggering antigens and further justify our approach that uses germline forms of pathogenic mAbs to uncover the initial antigenic targets of the immune system that lead to the subsequent autoimmune responses in autoimmune diseases. As walnut is well known to cause allergic diseases, our findings have a possible implication that allergens may trigger autoimmunity in addition to allergy. Moreover, this investigation may provide a paradigm for the etiological studies of other autoimmune diseases.