THU0241 ALTERATIONS OF THE FECAL MICROBIOTA ASSOCIATED WITH EXACERBATION OF LUPUS ACTIVITY BY HCMV PP65 422-439 IMMUNIZATION IN NZB/W F1 MICE
Authors: Y. C. Tsai, A. H. Hsieh, L. C. Wang, I. J. Chou, W. Y. Tseng, K. H. Yu, S. F. Luo, C. F. Kuo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Systemic lupus erythematosus (SLE) is a multifactorial disease. Gut microbiota is an important environmental factor for SLE 1 . The perturbation of gut microbiota is often observed at onset or during the disease course. The fragment of HCMV phosphoprotein 65 422-439 (HCMVpp65 422-439 ) containing B cell epitopes has been reported to elicit humoral immunity and accelerate the autoimmune response in murine lupus 2,3 . However, little is there to know about the interplay between viral trigger for SLE and the change of gut microbiota during lupus progression. Objectives: By using a murine lupus model with NZB/W F1, we investigated the differential alteration in gut microbiota associated with the progression of lupus disease in HCMVpp65 422-439 immunized mice and control mice. Methods: Ten weeks-old NZB/W F1 mice were given or not given an intraperitoneal injection of 100-μg HCMVpp65 422-439 peptide biweekly for four times. Fecal samples, urine and blood of mice were collected once every two weeks followed by 16S rRNA genes sequencing and ELISA tests. The pathological investigation of renal tissue from sacrificed mice was conducted at 24 weeks of mice age. Statistical analysis for dynamics and alteration of the gut microbiota as well as functional prediction of bacterial communities related to the progression of lupus-like activity was performed. Results: HCMVpp65 422-439 immunization results in the onset of lupus-like activities in NZB/W F1 mice with a higher titer of anti-dsDNA antibody, creatinine and proteinuria, and severe glomerular damage (figure 1). Also, higher diversity and increased family abundance of several bacterial species were observed in HCMVpp65 422-439 immunized mice (Table 1 and Figure 2a). The predicted metagenomic taxonomic profile in NZB/W F1 mice showed statistically significant enrichment of flagellar assembly, bacterial motility, and chemotaxis (Figure 2b). Spearman’s correlation analysis revealed that a significant association between the increased relative family abundance for Saccharimonadaceae, Marinifilaceae, Desulfovibrionaceae, and Rikenellaceae and HCMVpp65 422-439 induced lupus-like activity in NZB/W F1 mice (Figure 2c). Table 1. Significant test of microbial community structure between two groups MRPP Adonis Anosim Groups E-Δ P R 2 P R P Pre-disease vs. Control 0.43 0.1 0.77 0.1 1 0.112 Pre-disease vs. HCMVpp65 422-439 0.52 0.007 0.55 0.009 0.97 0.01 Control vs. HCMVpp65 422-439 0.45 0.013 0.35 0.014 0.58 0.019 Conclusion: Our results demonstrated that HCMVpp65 422-439 immunization induced the change in gut microbiota composition and suggested the association of gut microbiota alteration with lupus-like activity in NZB/W F1 mice. References: [1]Azzouz D, Omarbekova A, Heguy A, Schwudke D, Gisch N, Rovin BH, et al. Lupus nephritis is linked to disease-activity associated expansions and immunity to a gut commensal. Ann Rheum Dis. 2019;78(7):947-56. [2]Sebastiani GD, Iuliano A, Canofari C, and Bracci M. Cytomegalovirus infection in Systemic Lupus Erythematosus: report of four cases challenging the management of the disease, and literature review. Lupus. 2019;28(3):432-7. [3]HoHsieh A, Wang CM, Wu YJ, Chen A, Chang MI, and Chen JY. B cell epitope of human cytomegalovirus phosphoprotein 65 (HCMV pp65) induced anti-dsDNA antibody in BALB/c mice. Arthritis Res Ther. 2017;19(1):65 Disclosure of Interests: : None declared