THU0281 EXPLORING THE GENETIC DIVERSITY OF STAPHYLOCOCCUS AUREUS IN PATIENTS AFFECTED BY SYSTEMIC LUPUS ERYTHEMATOSUS: ASSOCIATION WITH DISEASE-RELATED FEATURES AND ACTIVITY

Abstract

Background:Infective factors play a central role in autoimmune diseases pathogenesis. It is possible to speculate that the host genotype could interact with genetic background of infective agents. We previously evaluated a large SLE cohort, observing the association between theS. Aureus(SA) carriage status and presence of a more active disease in terms of autoantibodies positivity.Objectives:We evaluated epidemiological, molecular characterization, genetic diversity and evolution of SA isolated from SLE patients by means of phylogenetic analysis.Methods:Consecutive SLE patients (ACR 1997 criteria) were enrolled: clinical/laboratory data were collected and nasal swab for SA identification was performed. On the basis of translation elongation factor (tuf) gene, a phylogenetic analysis was performed to investigate phylogenetic relationships and to assess significant clades in patients with persistent carriage status (nasal swab positive in two consecutive evaluation, performed 1 week apart). The first dataset was composed by seven SA tuf gene isolated from non-SLE individuals from different countries (downloaded from the GenBank database,https://www.ncbi.nlm.nih.gov/nucleotide/) and tuf gene SA collected from SLE patients enrolled in the present study.Results:We enrolled 118 patients (M/F 10/198; median age 45.5 years, IQR 13,2; median disease duration 120 months, IQR 144). Skin involvement is the most frequent disease manifestation (86 patients, 72.9%), followed by joint involvement (78 patients, 66.1%). Twenty-four patients (20.3%) were SA carriers (SA+), three of them resulted MRSA. SA+ patients showed a significantly higher prevalence of joint involvement (79.2%versus62.7%, P=0.01) and anti-dsDNA positivity (75.0%versus55.3%, P=0.004). Moreover, SA+ SLE showed a more active disease, in terms of SLEDAI-2k values [SA+: median 2 (IQR 3.75)versusSA-: median 0 (IQR 2), P=0.04). The phylogenetic analysis has been restricted on the 21 non-MRSA SA+ patients. The maximum likelihood phylogenetic tree of the first dataset revealed a statistically supported larger clade (A, N=17) and a smaller one (B, N=4; figure 1A). SLE patients located in the clade A showed a significantly higher prevalence of joint involvement (88.2%) in comparison with clade B (50.0%, P<0.0001) and SA- (62.7%, P<0.0001, figure 2B). Moreover, haematological manifestations were significantly more frequent in clade A patients (64.7%) compared with B (50.0%, P=0.004, figure 2C).Conclusion:The results of the present study confirmed the association between SA carriage status and disease activity, in terms of SLEDAI-2k values and anti-dsDNA positivity. The phylogenetic analysis ontufgene show a clustering ofSA+patients in two major clade (A and B). Interestingly thetufgenotype of clade A is significantly associated with a specific disease phenotype, characterized by joint involvement and positivity for anti-dsDNA. These findings support the hypothesis that bacterial genetic variants may be associated with specific disease features.