Thansita Bhunyakarnjanarat,1,2 Jiradej Makjaroen,3,4 Wilasinee Saisorn,2,5 Kankorn Hirunsap,1 Jidapond Chiewchengchol,1 Patcharee Ritprajak,6 Asada Leelahavanichkul1,2

Affiliations:
1 Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
2 Center of Excellence in Translational Research on Immunology and Immune-mediated Diseases (CETRII), Department of Microbiology, Faculty of Medicine, Bangkok, Thailand
3 Department of Transfusion Medicine and Clinical Microbiology, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand
4 Center of Excellence in Systems Biology, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
5 Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand
6 Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand

Abstract

Background: Although allergy might be another factor that exacerbates lupus as demonstrated by several
epidemiologic studies, the direct correlation between lupus activities and allergy is still in question.
Objective: To explore the correlation between allergic reaction and lupus activities.
Methods: The allergic asthma model using ovalbumin (OVA) administration in wildtype (WT) and Fc gamma receptor IIb deficient (FcgRIIb-/-) mice (a lupus-prone model) together with in vitro experiments on bone marrow-derived dendritic cells (DCs) were performed.
Results: At 2-weeks-post OVA, both WT and FcgRIIb-/- mice demonstrated similar allergic reaction as indicated by an elevation of IgE and IL-4 in serum with asthma-liked lung histology (lung weight, inflammatory score, and bronchial thickness) with increased spleen weight. Apoptosis in the lungs and spleens (activated caspase 3 immunohistochemistry) was detected only in OVA-administered FcgRIIb-/- mice. Surprisingly, OVA-administered FcgRIIb-/- mice, demonstrated active lupus nephritis, as indicated by anti-dsDNA, proteinuria, and renal immune complex deposition (immunohistochemistry analysis) implying an impact of allergy on lupus activities. Meanwhile, serum creatinine and gut permeability defect (FitC-dextran assay and endotoxemia) were not different between the FcgRIIb-/- mice with OVA versus with control. In parallel, FcgRIIb-/- DCs were more susceptible to activations by OVA and lipopolysaccharide (LPS) than WT DCs as demonstrated by CD80 with major histocompatibility complex II (MHC II) using flow cytometry analysis.
Conclusions: OVA-induced allergy in FcgRIIb-/- mice exacerbated lupus activity, possibly due to hyper-responsiveness of FcgRIIb-/- DCs over WT from the loss of inhibitory FcgRIIb. The proper control of allergy might be beneficial for lupus.
Key words: Ovalbumin, lupus, Asthma, FcgRIIb, Dendritic cells, T cells