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Epidemiology studies have shown that the prevalence of allergies in patients with Systemic Lupus Erythematosus (SLE) was higher than in those of normal, healthy subjects. Although many patients with SLE also have allergies, the immunological events triggering the onset and progression of the clinical manifestations of SLE by allergens have yet to be clarified. Our previous report showed that three autoantigens, Phosphoglycerate Kinase 1 (PGK-1), Triosephosphate Isomerase (TIM) and enolase were identified through the use of autologous serum in B cell lysate. This was derived from House Dust Mites (HDM) allergic SLE patients after Dp2 stimulation, where the concentration of anti-PGK-1 was significantly up-regulated after Dp2 stimulation, when compared to HDM allergic without SLE patients and healthy subjects. In this study, we further investigated Dp2 stimulated autoantigens (PGK-1 and TRIM-21) and autoantibodies (anti-PGK-1 and TRIM-21) production and their relationship with inflammasomal activation IL1β production. Both Peripheral Blood Mononuclear Cell (PBMC) and B cell lines derived from patients with Dermatopgagoides pteronyssinus (Dp)-allergic SLE was included in this study. CPPecp and siRNA knockdown were added to evaluate their effect on cell activation. Our results showed that Dp2 could up-regulate PGK-1,TRIM -21,antiPGK-1 and anti-TRIM-21 in B cell lines, and also up-regulate enolase and PGK-1 in PBMC. The expression of IL-1β and NLRP3 was also increased through Dp2 stimulation. Although both autoantigens and autoantibodies were upregulated, the increment of autoantigen and autoantibodies were abolished after being co-cultured with CPPecp. In the siRNA NLRP3 study only the increment of TRIM-21 and anti-PGK-1 was abolished. In conclusion, our study demonstrated that allergen exposure in the patients with HDM-sensitive SLE may play a role in the incremental expression of autoantigens and autoantibodies. In patients with Dp allergic SLE, Dp2 could upregulate the production of auto-antigen and auto-antibodies, while contributing to the proinflammatory cytokine secretion and disease activation. Dp2-induced auto-antigen and auto-antibody production could be abolished by being co-cultured with Dp2 and CPPecp, indicating that CPPecp has the potential to be a new immune-modulatory agent for the treatment of autoimmune diseases in the future. Introduction Systemic Lupus Erythematosus (SLE) is a multifactorial systemic autoimmune disorder which affects multiple organs including the skin, lungs, kidneys, and heart [1]. In some SLE patients, autoantibodies may target specific proteins in the cytosol or nucleus. These proteins are called autoantigens. Since these self-antigens are normally covered from the extracellular space by both the nuclear membrane and the cell membrane, the major issue is how these self-antigens are exposed or upregulated, and then detected by the immune system. In recent years, bystander activation of the immune system in SLE patients has been related to environment factors. Bystander activation means there is an indirect or nonspecific activation of autoimmune cells which is caused by the inflammatory environment present during infection [2]. This can lead to an enhanced processing and presentation of self antigens, which induces the expansion or spreading of the immune response towards different self-antigens [3, 4]. House Dust Mites (HDM) is the most commonly found aeroallergens worldwide. Dust mite allergens similar to the environmental pathogen, Lipopolysaccharide (LPS), can combine with Toll Like Receptors (TLR) to cause an inflammatory cell-mediate immune response. Its major allergen, Dermatophagoides pteronyssinus 2 (Dp2), can internalize to epithelium and augment toll-like receptormediated proinflammatory signaling with IL-6 and IL-8 secretion [5]. Dp2 is able to both trigger human B lymphocyte activation, and induce B cell proliferation. Dp2 can induce expressionof IL1β, TNF-α and IL-8, and up-regulate MD2, TLR4 induction in B cells, which enhance the host’s immune response [6]. Dp2 can induce bystander activation of B cells derived from patients with SLE [7]. Whether SLE patients with hypersensitivity to Dp2 were more susceptible to inflammasome activation and thus prone to autoantibody production remains unclarified.

Dp2-Induce Autoantigen/Autoantibody Production from Patients with Systemic Lupus Erythematosus and Its Modulation by Cppecp