THU0233 ANTIBODIES AGAINST COMMENSAL STREPTOCOCCAL SPECIFIC PROTEIN (SSP) AND MITOCHONDRIAL IMMUNO- DOMINANT PROTEIN(MIP) IN DIAGNOSIS OF SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND OTHER SYSTEMIC AUTOIMMUNE DISEASES
Authors: C. H. Hsu, C. J. Jung, Y. M. Kuo
Journal: Annals of the Rheumatic Diseases (2020)

Background: Streptococcal infection has well known to cause rheumatic fever with various presentations similar to SLE. Besides, both streptococcal-blood stream infection and SLE had aggravated neutrophil extracellular traps (NETs) formation. Previously, we did report a streptococcal induced endocarditis rat model, and identified layers of neutrophil extracellular traps (NETs). According to our findings, specific immunoglobulin G (IgG) could bridge bacteria to host and these IgGs are required to induce the formation of NETs. Whether oral commensal bacteria could induce pathogenic antibodies which promote NET formation remained unknown. Objectives: So we aimed to search for novel autoantibodies in SLE through antibody repertoire screening which recognize whole proteins derived from Streptococcus mutans , and investigated to find cross-reactive antibodies presented in the serum of lupus patients and do the correlation between serum MPO(myeloperoxidase)-DNA, a marker of NETosis. Methods: The streptoccocal specific protein (SSP) was identified through LC-MS and by a proteomics survey. We then purified the target protein in streptococci with expression vector, and antibody level will be detected quantitatively. We recruited patients with SLE, other systemic autoimmune diseases (AIDs) patients to elucidate the performance of this biomarker. Besides, we pursued the Basic Local Alignment Search Tool (BLAST) and searched for cross-reactive autoantigens. Results: 79 lupus patients and 95 patients with other systemic autoimmune disease were enrolled. By using cut-off value 1.06(set according to area under the receiver operating characteristic curve) of anti-SSP o.d. value (174 samples), 27 of 79 (34.2%) SLE patients have positive results while only 7/95 (7.4%) was detected in control group. The specificity and sensitivity of the anti-SSP for diagnosis of SLE was 92.6% and 34.2% respectively. According to BLAST and B cell–epitope prediction algorithms, The P32-55 epitopes were identified and we synthesized a highly immunogenic and surface-accessible epitope related protein. We named the protein to be MIP (mitochondrial immuno-dominant protein.) Most of the sera from SLE patients could recognize MIP and anti-MIP correlated with serum MPO-DNA(r=0.41, p=0.039). Conclusion: The novel anti-SSP antibody against commensal streptococcal specific protein can differentiate SLE and other AIDs. Further investigation to determinate whether the anti-SSP antibody or the associated immune-complex could induce or aggravate NETs formation is warranted. References: [1]Sci Transl Med 2011; 3(73):73ra19-73ra19. [2]J Biomed Sci. 2014 17;21:23. [3]Circulation. 2015; 131:571–581 [4]Nat Med. 2016 22(2):146-53. Disclosure of Interests: : Che-Hao Hsu: None declared, Chiau-Jing Jung: None declared, Yu-Min Kuo Speakers bureau: Novartis, Pfizer, Rothe, Janssen, Abbvie, UCB, Chugai, Bristol Myers Squibb, Amgen and Astellas