Dp2-Induced Autoantigen/Autoantibody Production From Patients With Systemic Lupus Erythematosus Is Done Through AIM2 And Not NLRP3

Systemic Lupus Erythematosus (SLE) is a disease characterized by the production of autoantibodies against different autoantigens, including double stranded DNA (dsDNA). AIM2 (Protein absent in melanoma 2) is one of the inflammasome proteins which can directly bind to dsDNA. It is therefore possible to speculate that AIM2 may contribute to the disease development of SLE. B cell lines obtained from patients with Dp-allergic SLE were used to investigate the involvement of AIM2 in autoantibody production. The obtained B cells were then cultured with Dp2 for inflammasome activation. The cells-cultured pellet and supernatant were subsequently collected for the measurement of autoantigens, autoantibodies and inflammatory cytokines. The inflammasome of AIM2 and NLRP3 was measured and correlated with autoantibodies production. The B cells were pretreated with siRNA of AIM2, followed by Dp2 stimulation to confirm the activation of AIM2. The results showed that Dp2 could induce inflammasome activation with an increased expression of both NLRP3 and AIM2, which was associated with the production of TRIM21/PGK1, anti-TRIM21/anti-PGK-1 and IL8/IL-1β. In the siRNA AIM2 study, Dp2 induced autoantigen/autoantibody/cytokine production could be down-regulated by siRNA in association with a decreased expression of AIM2. Dp2-induced expression of NLRP3 and AIM2 can both be down-regulated by CPP ECP. In Conclusion: Dp2 induced expression of NLRP3 and AIM2 is associated with autoantigen and autoantibody production from B cells derived from Dp-allergic SLE. These autoantigens/autoantibodies can be downregulated only by siRNA AIM2, and not by NLRP3. Introduction Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by various systemic organ and tissue damage caused by inflammasome activation. Recently enhanced inflammasome activity in SLE has been previously reported [1]. A broad range of microbial, host and environmental triggers of inflammasome have been reported. There are five receptor proteins which have been confirmed to assemble inflammasomes, and include Non-binding Oligomerization Domain (NOD), Leucine-Rich Repeat (LRR)-containing protein, (NLR) family members NLRP1, NLRP3 and NLRP4, as well as the proteins absent in melanoma 2 (AIM2) and pyrin [2, 3]. AIM2 is a new type of inflammasome which is similar to NLR proteins, and can regulate caspase-1 activation and Interleukin 1 beta (IL-1β) production in response to viral, host and bacterial dsDNA, and in response to the dsDNA virus vaccinia [4]. AIM2 appears to recognize dsDNA from a variety of microbial species, including those from mammalian cells. With the existence of a dedicated cytosolic DNA receptor, AIM2 was postulated on the basis of the observation that both microbial and host DNA induce caspase 1 activation in an ASC-dependent manner, but independently of NLRP3, Toll-like Receptors (TLR) or interferon signaling [5]. A link between AIM2 and several human diseases has been previously established. An increased AIM2 expression is associated with psoriasis, abdominal aortic aneurysm and Systemic Lupus Erythematosus (SLE) [6-8]. In the case of psoriasis, autoinflammation could be linked to AIM2-