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Hua-Zhi Ling, Shu-Zhen Xu, Rui-Xue Leng, Jun Wu, Hai-Feng Pan, Yin-Guang Fan, Bin Wang, Yuan-Rui Xia, Qian Huang, Zong-Wen Shuai ... Show more Author Notes Rheumatology, kez634, https://doi.org/10.1093/rheumatology/kez634 Published: 03 January 2020 Abstract Objective Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis. Methods Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies. Results A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A. Conclusion The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases. Rheumatology key messages Many differentially expressed autoantibodies were newly identified in SLE patients. Autoantibody panels discovered in this study may be good biomarkers for SLE diagnosis. Some associations exist between the autoantibodies identified in this study and clinical characteristics of SLE patients. kez634.pdf
SLE Breakthrough Finds a Link Between Microbial Translocation and Autoantibodies (©AysezgicmeliShutterstock.com) Gregory M. Weiss, M.D. August 7, 2019 Lupus, Modern Medicine News, News, Rheumatology A previously unknown direct relationship has been found between microbial translocation from the gastrointestinal tract and autoantibody levels in patients with systemic lupus erythematosus. The findings by, Gary Gilkeson, M.D., and Wei Jiang, M.D., of the Medical University of South Carolina in Charleston, appear in the May 20 online issue of Arthritis and Rheumatology. The authors state, “An understanding of the mechanism of autoantibody induction in systemic lupus erythematosus (SLE) can lead to the development of therapeutic targets that prevent autoantibody production thereby slowing disease onset, mitigating downstream inflammation and reducing tissue damages.” Systemic lupus erythematosus is a chronic autoimmune mediated inflammatory disease that results from a loss of tolerance to the patient’s own antigens leading to autoantibody production. It is known that genetic factors influence the development of lupus leading to clustering of the disease within families. The source of autoantibody production in systemic lupus erythematosus remains elusive and is likely multifactorial with genetic, environmental, immunologic, and hormonal factors contributing to development of the disease. Recent research has implicated increased intestinal permeability in the pathogenesis of autoimmune disease. While under normal conditions the gastrointestinal tract serves as a barrier to environmental antigens, however, in certain disease states, this barrier may be compromised allowing translocation of gut microbes into the bloodstream. The authors sought to determine the role of microbial translocation in systemic lupus erythematosus. They examined lupus patients and their first-degree relatives comparing them to healthy controls. Two cohorts were included in the study. The first group consisted of 18 unrelated healthy control subjects and 18 first-degree relatives of systemic lupus erythematosus patients. The second included 19 healthy controls and 21 lupus patients. Plasma autoantibodies and lipopolysaccharide levels were measured and DNA bacterial DNA was extracted from plasma to determine if translocation had occurred. From the bacterial DNA microbiome species was determined. Auto-antigen array demonstrated higher plasma levels of a large spectrum of autoantibodies in systemic lupus erythematosus patients and first-degree relatives of lupus patients compared to healthy controls. Four representative lupus-related IgG autoantibodies including anti-double stranded DNA, anti-nucleosome, anti-single stranded DNA and anti-chromatin were increased in lupus patients and first-degree relatives compared to healthy control subjects. Compared to unrelated healthy control subjects, systemic lupus erythematosus patients and parents or children who were first-degree relatives had increased microbial translocation as evidenced by plasma lipopolysaccharide levels. First-degree relatives of lupus patients but not lupus patients themselves had decreased intestinal species diversity when compared to healthy controls. Take-home points and final thoughts First-degree relatives of systemic lupus erythematosus patients also have significantly elevated levels of lupus related autoantibodies. Increased levels of lipopolysaccharide in these patients are consistent with prior research linking infection, bacterial translocation and autoimmunity. The authors state, “The increased translocation of bacterial products into the systemic circulation from the permeable mucosa suggests that insights into autoimmune pathology can be gained from studying the circulating microbiome as opposed to other sites.” In a letter to the editor the authors discuss why they believe bacterial diversity was decreased in relatives but not in lupus patients themselves. They found after reanalyzing the data that diversity differences did not occur within a specific racial group but did between different races. They point out that, “while race may play a role in differences in circulating microbiome diversity, additional studies are needed to confirm this hypothesis.” Systemic lupus erythematosus is a very complex disease with an etiology that has remained elusive. The authors have discovered a possible infectious cause of lupus that could lead to focus on intestinal integrity and possibly uncover medications that we are using that compromise gut barrier. While the discovery of bacterial translocation in lupus opens the door for future investigation into preventing this from happening, the sheer number of different possible causes for systemic lupus erythematosus remains daunting. With continued efforts like those of the authors, we take important steps toward understanding lupus in the hopes of improving the quality of life of those who suffer from it. REFERENCE Elizabeth Ogunrinde, Zejun Zhou, Zhenwu Luo, et al. "A link between plasma microbial translocation, microbiome, and autoantibody development in first-degree relatives of systemic lupus erythematosus patients." Arthritis and Rheumatology. 2019 May 20. doi: 10.1002/art.40935 https://www.rheumatologynetwork.com/lupus/sle-breakthrough-finds-link-between-microbial-translocation-and-autoantibodies?rememberme=1&elq_mid=8392&elq_cid=1830808&GUID=9D824BFE-EF27-47A3-BAE0-900DC34C90C7