The Autoantigen Repertoire and the Microbial RNP World

Williams, Sandra G.; Wolin, Sandra L.

doi:10.1016/j.molmed.2021.02.003

Cited by 6 publications

(4 citation statements)

References 143 publications

(142 reference statements)

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“…Therefore, we further explored whether adsorption of BNV(+&−) could lead to enrichment of self-antigens and elevation of their antibody levels. First, BNV(+) and BNV(−) did capture many autoantigens (Figure S8A), including ribonucleoprotein particles (RNPs) such as SSB and SRP54, as well as other enzymes and proteins like SAE1 and FBL, which would be associated with autoimmune disorders such as desiccation syndrome, SLE, systemic sclerosis, and dermatomyositis. − We examined the levels of SSB and SRP antibodies in serum at different time points after administration, and as shown in Figure S8B, BNV(+&−) did not significantly induce the production of autoantigen-associated antibodies, proving its low risk to induce autoimmune disorders. It made a good beginning for the safety application of BNV(+&−).…”

Section: Resultsmentioning

confidence: 99%

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

Li,

Jiang,

Han

et al. 2023

ACS Nano

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Cancer vaccine gains great attention with the advances in tumor immunology and nanotechnology, but its long-term efficacy is restricted by the unsustainable immune activity after vaccination. Here, we demonstrate the vaccine efficacy is negatively correlated with the tumor burden. To maximum the vaccineinduced immunity and prolong the time-effectiveness, we design a priming−boosting vaccination strategy by combining with radiofrequency ablation (RFA), and construct a bisphosphonate nanovaccine (BNV) system. BNV system consists of nanoparticulated bisphosphonates with dual electric potentials (BNV(+&−)), where bisphosphonates act as the immune adjuvant by blocking mevalonate metabolism. BNV(+&−) exhibits the spatial and temporal heterogeneity in lymphatic delivery and immune activity. As the independent components of BNV(+&−), BNV(−) is drained to the lymph nodes, and BNV(+) is retained at the injection site. The alternately induced immune responses extend the time-effectiveness of antitumor immunity and suppress the recurrence and metastasis of colorectal cancer liver metastases after RFA. As a result, this trinity system integrated with RFA therapy, bisphosphonate adjuvant, and spatiotemporal immune effect provides an orientation for the sustainable regulation and precise delivery of cancer vaccines.

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Section: Resultsmentioning

confidence: 99%

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

Li,

Jiang,

Han

et al. 2023

ACS Nano

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“…A variety of triggers—from infectious to malignant—may cause the convergence of the immunological response to the selection of stereotyped B cells that have evaded immune tolerance checkpoints [ 30 ]. Recent interest in the role of the microbiome and molecular mimicry may help explain the emergence of stereotyped autoantibodies and associated SADs [ 31 ]. Indeed, the further exploration of anti-Ro52/TRIM21 through epitope and proteomic profiling may help shed light on the origins and progression of the autoantibody and be an avenue for advanced diagnostic and therapeutic strategies [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Ro52/TRIM21 serological subsets identify differential clinical and laboratory parameters

2022

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Introduction Anti-Ro52/tripartite motif-containing protein 21 (TRIM21) IgG is one of the most common autoantibodies found in systemic autoimmune diseases and is typically found in conjunction with anti-Ro60 and/or anti-La. A retrospective, cross-sectional study was undertaken to examine the clinical and laboratory features of two serological subsets: patients with anti-Ro52/TRIM21 autoantibodies in the absence of anti-Ro60 and anti-La (isolated anti-Ro52/TRIM21) and patients with anti-Ro52/TRIM21 in the presence of anti-Ro60 and/or anti-La. Methods Over a 12-month period, patients tested positive for anti-Ro52/TRIM21 via line immunoassay (LIA) at the Westmead Hospital (Australia) immunopathology laboratory were included. The presence of anti-Ro60 and/or anti-La via same LIA was noted. Associated laboratory and medical records were perused to extract demographic, laboratory, and clinical information. Results There were 346 patients within the study period, and 39.9% of the patients positive for anti-Ro52/TRIM21 lacked anti-Ro60/anti-La autoantibodies. Isolated anti-Ro52/TRIM21 patients tend to be older, have lower anti-Ro52/TRIM21 titres, have lower rheumatoid factors, and have lower proportions of neutropaenia compared to patients who were positive for anti-Ro52/TRIM21 and anti-Ro60/La. This occurred independent to diagnoses of Sjögren’s syndrome or systemic lupus erythematosus. Coexisting neurological syndromes, pulmonary pathologies, and malignancies were more prevalent in the isolated anti-Ro52/TRIM21 subset. Conclusions Patients with isolated anti-Ro52/TRIM21 tend to have distinct and important clinical and laboratory associations. It is unclear if these patients evolve or remain a stable subset and how they originate immunologically. Longitudinal and prospective studies are required to ascertain the overall predictive and prognostic value of this stratification. Key Points• Anti-Ro52/TRIM21 is an autoantibody found in autoimmunity and non-immunological conditions.• Sixty percent of anti-Ro52/TRIM21 patients are positive for anti-Ro60.• Isolated anti-Ro52/TRIM21 has reduced anti-Ro52/TRIM21 and rheumatoid factor titres.• Isolated anti-Ro52/TRIM21 is associated with anaemia and malignancies.

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“…Molecular or antigenic mimicry pre-supposes a common immunological epitope between a microbe and the host for cross-immune reactions. In autoimmunity and autoimmune disease, nucleic acids and their binding proteins are included in the repertoire of autoantigens [70,77]. Why and how ribonucleoproteins (RNPs) drive this process is still unclear, but their prevalence could be partly explained by their ability to act as ligands for toll-like receptors (TLRs), which are part of the immune system.…”

Section: Relationship Between the Microbiota And Autoimmunitymentioning

confidence: 99%

“…However, in this process, it is possible that autoimmunity and some of these ribonucleoprotein particles may originate from molecular mimicry at a microbial ortholog level. One of the best examples of molecular mimicry in individuals as a mechanism responsible for the development of autoimmune disease is that associated with rheumatic fever, following infections with group-A β-hemolytic Streptococci [70,77,78]. Epitope spread refers to autoimmune responses to autoepitopes, occurring when the autoantigen is released in an inflammatory response.…”

Section: Relationship Between the Microbiota And Autoimmunitymentioning

confidence: 99%

Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?

et al. 2022

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The use of innovative approaches to elucidate the pathophysiological mechanisms of autoimmune diseases, as well as to further study of the factors which can have either a positive or negative effect on the course of the disease, is essential. In this line, the development of new molecular techniques and the creation of the Human Genome Program have allowed access to many more solutions to the difficulties that exist in the identification and characterization of the microbiome, as well as changes due to various factors. Such innovative technologies can rekindle older hypotheses, such as molecular mimicry, allowing us to move from hypothesis to theory and from correlation to causality, particularly regarding autoimmune diseases and dysbiosis of the microbiota. For example, Prevotella copri appears to have a strong association with rheumatoid arthritis; it is expected that this will be confirmed by several scientists, which, in turn, will make it possible to identify other mechanisms that may contribute to the pathophysiology of the disease. This article seeks to identify new clues regarding similar correlations between autoimmune activity and the human microbiota, particularly in relation to qualitative and quantitative microbial variations therein.

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The Autoantigen Repertoire and the Microbial RNP World

Cited by 6 publications

References 143 publications

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

A Trinity Nano-Vaccine System with Spatiotemporal Immune Effect for the Adjuvant Cancer Therapy after Radiofrequency Ablation

Anti-Ro52/TRIM21 serological subsets identify differential clinical and laboratory parameters

Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?

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