Biomarkers For Autoimmune Diseases Research Articles

Limited Biomarker Potential for IgG Autoantibodies Reactive to Linear Epitopes in Systemic Lupus Erythematosus or Spondyloarthropathy.

Autoantibodies are commonly used as biomarkers in autoimmune diseases, but there are limitations. For example, autoantibody biomarkers have poor sensitivity or specificity in systemic lupus erythematosus and do not exist in the spondyloarthropathies, impairing diagnosis and treatment. While autoantibodies suitable for strong biomarkers may not exist in these conditions, another possibility is that technology has limited their discovery. The purpose of this study was to use a novel high-density peptide array that enables the evaluation of IgG binding to every possible linear antigen in the entire human peptidome, as well as a novel machine learning approach that incorporates ELISA validation predictability in order to discover autoantibodies that could be developed into sensitive and specific markers of lupus or spondyloarthropathy. We used a peptide array containing the human peptidome, several viral peptidomes, and key post-translational modifications (6 million peptides) to quantify IgG binding in lupus, spondyloarthropathy, rheumatoid arthritis, Sjögren's disease, and control sera. Using ELISA data for 70 peptides, we performed a random forest analysis that evaluated multiple array features to predict which peptides might be good biomarkers, as confirmed by ELISA. We validated the peptide prediction methodology in rheumatoid arthritis and COVID-19, conditions for which the antibody repertoire is well-understood, and then evaluated IgG binding by ELISA to peptides that we predicted would be highly bound specifically in lupus or spondyloarthropathy. Our methodology performed well in validation studies, but peptides predicted to be highly and specifically bound in lupus or spondyloarthropathy could not be confirmed by ELISA. In a comprehensive evaluation of the entire human peptidome, highly sensitive and specific IgG autoantibodies were not identified in lupus or spondyloarthropathy. Thus, the pathogenesis of lupus and spondyloarthropathy may not depend upon unique autoantigens, and other types of molecules should be sought as optimal biomarkers in these conditions.

MicroRNAs as Key Regulators in RA and SLE: Insights into Biological Functions.

MicroRNAs (miRNAs) are non-coding RNA molecules that bind to mRNAs to regulate gene expression. Since changes in miRNA expression levels have been found in a variety of autoimmune illnesses, miRNAs are important in autoimmune diseases. MiRNAs serve not only as pathogenic factors and biomarkers for autoimmune diseases but also as important targets for disease therapeutics. Although miRNA-based treatments are still in the research stage, in-depth investigations into the biological functions of miRNAs have significantly enhanced our understanding of their mechanisms in autoimmune diseases. The purpose of this review is to summarize the biological functions of miRNAs, their roles in rheumatoid arthritis and systemic lupus erythematosus, therapeutic strategies, and challenges.

Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus.

There are several autoimmune and rheumatic diseases affecting different organs of the human body. Multiple sclerosis (MS) mainly affects brain, rheumatoid arthritis (RA) mainly affects joints, Type 1 diabetes (T1D) mainly affects pancreas, Sjogren's syndrome (SS) mainly affects salivary glands, while systemic lupus erythematosus (SLE) affects almost every organ of the body. Autoimmune diseases are characterized by production of autoantibodies, activation of immune cells, increased expression of pro-inflammatory cytokines, and activation of type I interferons. Despite improvements in treatments and diagnostic tools, the time it takes for the patients to be diagnosed is too long, and the main treatment for these diseases is still non-specific anti-inflammatory drugs. Thus, there is an urgent need for better biomarkers, as well as tailored, personalized treatment. This review focus on SLE and the organs affected in this disease. We have used the results from various rheumatic and autoimmune diseases and the organs involved with an aim to identify advanced methods and possible biomarkers to be utilized in the diagnosis of SLE, disease monitoring, and response to treatment.

Biomarkers in autoimmune diseases of the central nervous system.

The autoimmune diseases of the central nervous system (CNS) represent individual heterogeneity with different disease entities. Although clinical and imaging features make it possible to characterize larger patient cohorts, they may not provide sufficient evidence to detect disease activity and response to disease modifying drugs. Biomarkers are becoming a powerful tool due to their objectivity and easy access. Biomarkers may indicate various aspects of biological processes in healthy and/or pathological states, or as a response to drug therapy. According to the clinical features described, biomarkers are usually classified into predictive, diagnostic, monitoring and safety biomarkers. Some nerve injury markers, humoral markers, cytokines and immune cells in serum or cerebrospinal fluid have potential roles in disease severity and prognosis in autoimmune diseases occurring in the CNS, which provides a promising approach for clinicians to early intervention and prevention of future disability. Therefore, this review mainly summarizes the potential biomarkers indicated in autoimmune disorders of the CNS.

Biology of interleukin-37 and its role in autoimmune diseases (Review).

Autoimmune diseases (AIDs) are characterized by dysfunction and tissue destruction, and recent studies have shown that interleukin (IL)-37 expression is dysregulated in AIDs. Among cytokines of the IL-1 family, most are pro-inflammatory agents, and as an anti-inflammatory cytokine, IL-37 may have the potential to alleviate excessive inflammation and can be used as a ligand or transcription factor that is involved in regulating innate and adaptive immunity. IL-37 plays important roles in the development of AIDs. This review summarizes the biological characteristics and functions of IL-37 and discusses the potential of IL-37 as a therapeutic target for effective cytokine therapy and as a biomarker in AIDs.

Clinical Significance of Antinucleolar Antibodies: Biomarkers for Autoimmune Diseases, Malignancies, and others.

Nucleolar staining is one of the standard patterns in immunofluorescence antinuclear antibodies (ANA), seen in 5-9% of ANA in various conditions. Antinucleolar antibodies (ANoA) are classified into 3 patterns in the International Consensus on ANA Patterns (ICAP) classification; AC-8 homogeneous pattern, AC-9 clumpy pattern, and AC-10 punctate pattern. Specificities known to show AC-8 include anti-Th/To, -PM-Scl, -nucleophosmin/B23, -nucleolin/C23, -No55, and others. AC-9 is seen by anti-fibrillarin/U3RNP and AC-10 by anti-RNA polymerase I and hUBF/NOR-90. ANoA has been classically known to be associated with scleroderma (SSc) and the characterization of nucleolar antigens identified several autoantigens recognized by SSc autoantibodies. The clinical association of anti-Th/To, PM-Scl, fibrillarin/U3RNP, and RNA polymerase I with SSc or SSc-overlap syndrome is well established, and commercial assays are developed. Anti-hUBF/NOR90, nucleophosmin/B23, and nucleolin/C23 are known for decades and reported in systemic autoimmune rheumatic diseases (SARDs), malignancies, graft versus host disease (GVHD), and others; however, their clinical significance remains to be established.

Long noncoding RNA intersectin\xa01-2 gradually declines during adalimumab treatment, and its reduction correlates with treatment efficacy in patients with ankylosing spondylitis

Previous studies show that long noncoding RNA intersectin 1-2 (lnc-ITSN1-2) promotes the inflammation process and serves as a potential biomarker in autoimmune diseases, except for ankylosing spondylitis (AS). Therefore, this study aimed to explore the correlation of baseline lnc-ITSN1-2 expression with disease risk and activity of AS, and to investigate its longitudinal change with treatment response to a tumour necrosis factor alpha (TNFα) inhibitor in patients with AS. In total, 63 patients with AS receiving 12-week adalimumab treatment were included and their baseline clinical features were collected. Lnc-ITSN1-2 expression in peripheral blood mononuclear cells (PBMC) of patients with AS was detected by reverse transcription quantitative polymerase chain reaction. Meanwhile, Assessment in Spondyloarthritis International Society (ASAS) 40 response was evaluated at week 2 (W2), W4, W8, and W12. According to the ASAS40 response status at W12, patients with AS were classified into responders and non-responders. PBMC lnc-ITSN1-2 expression was also determined in healthy controls (N = 60). Lnc-ITSN1-2 expression was elevated in patients with AS compared to controls (P < 0.001). Baseline lnc-ITSN1-2 expression was positively associated with C-reaction protein (CRP) (P = 0.021), interleukin (IL)-1β (P = 0.020), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score (P = 0.040), and Ankylosing Spondylitis Disease Activity score with C-reactive protein (ASDASCRP) (P = 0.045) in patients with AS. Furthermore, lnc-ITSN1-2 expression declined during the treatment with adalimumab (P < 0.001). Notably, this reduction was more obvious in responders than non-responders. In conclusion, declined lnc-ITSN1-2 expression during the TNFα inhibitor treatment correlates with good treatment efficacy in patients with AS, suggesting its clinical value for AS management.

Clinical Biomarkers in Otolaryngology-Head and Neck Surgery: Autoimmune Diseases.

The purpose of this article is to review the literature and compile promising and clinically relevant biomarkers in autoimmune disease related to otolaryngology-head and neck surgery. Narrative review. Pubmed and Google Scholar were queried using combined key words such as "biomarkers" and "otolaryngology." Additional queries were made with combined key words such as "biomarkers" and a particular subspecialty such as "autoimmune" or "Meniere's" to maximize yield of relevant titles. Subsequently, specific biomarkers identified, such as "anti-TPO-antibodies," were used as key words. Relevant titles were reviewed and selected for abstract review. Applicable abstracts were then selected for review of the full text. Biomarkers that are currently in clinical use for the management of autoimmune diseases within the field of otolaryngology were included in this review. The compiled biomarkers were then detailed individually regarding their molecular characteristics, function, and clinical significance. Based on this literature review, there are several biomarkers currently in clinical use within the field of otolaryngology relating to autoimmune diseases. The majority of these biomarkers are in the form of proteins such as Cogan peptide and c-ANCA. This survey may serve as a comprehensive resource on biomarkers for autoimmune diseases in clinical otolaryngology.

Comprehensive analysis of immunoglobulin and clinical variables identifies functional linkages and diagnostic indicators associated with Behcet\u2019s disease patients receiving immunomodulatory treatment

BackgroundBehcet’s disease (BD) is a relapsing systemic vascular autoimmune/inflammatory disease. Despite much effort to investigate BD, there are virtually no unique laboratory markers identified to help in the diagnosis of BD, and the pathogenesis is largely unknown. The aim of this work is to explore interactions between different clinical variables by correlation analysis to determine associations between the functional linkages of different paired variables and potential diagnostic biomarkers of BD.MethodsWe measured the immunoglobulin proteome (IgG, IgG1–4, IgA, IgA1–2) and 29 clinical variables in 66 healthy controls and 63 patients with BD. We performed a comprehensive clinical variable linkage analysis and defined the physiological, pathological and pharmacological linkages based on the correlations of all variables in healthy controls and BD patients without and with immunomodulatory therapy. We further calculated relative changes between variables derived from comprehensive linkage analysis for better indications in the clinic. The potential indicators were validated in a validation set with 76 patients with BD, 30 healthy controls, 18 patients with Takayasu arteritis and 18 patients with ANCA-associated vasculitis.ResultsIn this study, the variables identified were found to act in synergy rather than alone in BD patients under physiological, pathological and pharmacological conditions. Immunity and inflammation can be suppressed by corticosteroids and immunosuppressants, and integrative analysis of granulocytes, platelets and related variables is likely to provide a more comprehensive understanding of disease activity, thrombotic potential and ultimately potential tissue damage. We determined that total protein/mean corpuscular hemoglobin and total protein/mean corpuscular hemoglobin levels, total protein/mean corpuscular volume, and plateletcrit/monocyte counts were significantly increased in BD compared with controls (P < 0.05, in both the discovery and validation sets), which helped in distinguishing BD patients from healthy and vasculitis controls. Chronic anemia in BD combined with increased total protein contributed to higher levels of these biomarkers, and the interactions between platelets and monocytes may be linked to vascular involvement.ConclusionsAll these results demonstrate the utility of our approach in elucidating the pathogenesis and in identifying novel biomarkers for autoimmune diseases in the future.

Plasma microRNA levels in childhood IgA vasculitis.

Immunoglobulin A vasculitis (IgAV) is the most common form of childhood systemic vasculitis. It is mostly self-limiting and characterized by skin, joint, gastrointestinal tract, and kidney involvement. Microribonucleic acids (miRNAs) are 18-25 base-long non-coding RNA group acting on gene expression. They have been shown to be effective on the immune system studies to date. In our study, 24 IgAV children with skin and joint involvement and 24 healthy children were included. Five different miRNAs (miR-33, miR-34, miR-122, miR-204, and miR451) known to be expressed in plasma and related with autoimmunity pathogenesis were evaluated. miRNAs were compared between the active period of the disease, the post-treatment period, and the healthy group using the real-time PCR method. Expression levels of miRNA-33 and miRNA-34 increased significantly in active period of the patients compare with inactive period and control groups. The expression levels of miRNA-122 and miRNA-204 decreased significantly in active period of the patients compare with other two groups. There was no significant difference in miRNA-451 levels. With the experience we gained from our recent studies, we think that miRNA-204 may be a significant biomarker in autoimmune diseases. Our study is the first study between IgAV and miRNAs in children. More studies are needed to reveal this relationship. Key Points • This is the first paper to show the relationship between miRNAs and childhood IgAV. • It will provide a new perspective to evaluate the pathogenesis of the disease.

Pemphigus Foliaceous in a Dog - Clinical and Laboratorial Assessment

Background: The pemphigus complex is defined as a group of blistering autoimmune diseases that affects skin and mucous membrane. Pemphigus foliaceous is the most common disease in this group, being characterized by the production of autoantibodies against keratinocyte adhesion molecules. The treatment is based on the use of immunosuppressive drugs and requires constant monitoring to assess inflammatory control as well as side effects of therapy. Based on that, the aim of this study was to report the clinical and laboratorial follow-up of a canine with pemphigus foliaceous.Case: An 11-year-old male neutered mongrel dog, weighing 9.8 kg, was presented with a main complaint related to disseminated pruritus and lesions in face, trunk and limbs. Dermatological examination revealed meliceric crusts, epidermal collars and diffuse pustules in inguinal, abdominal, face, limbs, ears and thoraco-lumbar regions. Cytological examination was performed, revealing inflammatory and acantholytic cells and absence of bacterial cells. Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatible with canine pemphigus foliaceous. Hemoto-biochemical analysis revealed a leukocytosis due to increased neutrophil count. Systemic treatment with high dose of prednisolone (2.0 mg/kg) and azathioprine (2.5 mg/kg) was proposed, while topical therapy with a 3% chlorhexidine shampoo was used to prevent secondary bacterial infections. The patient improved the dermatological clinical signs, being possible to observe a reduction of systemic and tissue inflammatory process. After 90 days of therapy, there was a partial loss of hair body coverage, associated with follicular lesions, and after 180 days of therapy it was possible to notice a new hair mantle, without visible areas of inflammation.Discussion: The described clinical case demonstrates the clinical and laboratorial follow-up of a patient with naturally occurring canine pemphigus foliaceus. The main clinical characteristic of this disease is the formation of generalized pustular lesions, affecting regions such as the head, ear pinnae and limbs, which induced the diagnostic suspicion in the reported patient, in addition to the clinical history associated with complementary exams. In tissue evaluation, a pyogranulomatous inflammatory process was observed, with a marked presence of neutrophils and macrophages, which migrate from the dermis towards the epidermis. In systemic leukocyte analysis, an increase in the total leukocyte count was observed, due to the increase in circulating neutrophils. The therapy was based in use of a high dose of prednisolone associated with azathioprine. The following hemato-biochemical evaluations revealed a gradual reduction of systemic inflammatory process. Attention is drawn to neutrophil to lymphocyte ratio, which is a low-cost biomarker and less sensitive to pathophysiological changes when compared to individual leukocyte count. This parameter has been gaining visibility as a potential method of monitoring chronic inflammatory diseases. In veterinary medicine, its use is limited, with no reports related to canine pemphigus foliaceous in Brazil. After clinical and hematological improvement, prednisolone dose was slowly reduced, in order to avoid side effects. After clinical improvement, only azathioprine was maintained, in order to prevent critical flares. This report provides a clinical and laboratorial follow-up of a canine with pemphigus foliaceous, as well as it is the first one to describe the use of neutrophil to lymphocyte ratio to monitor therapeutic progression. New studies and reports involving this biomarker in autoimmune diseases monitoring are encouraged.

PROSPECTS FOR ANTI-B-CELL THERAPY IN IMMUNO-INFLAMMATORY RHEUMATIC DISEASES

Impaired B-cell immunological tolerance plays a central role in the pathogenesis of immuno-inflammatory rheumatic diseases (IIRD). B-cells link innate and acquired immunity: they express Toll-like receptors that respond to danger signals; act as antigen-presenting cells; induce an antigen-specific immune response; determine the development of immunological memory; and synthesize a wide range of cytokines that regulate (stimulate or suppress) an immune response and inflammation. In IIRD, there are metabolic and B-cellular signaling disturbances that lead to defects in B-regulatory, T-regulatory, follicular T-helper, and dendritic cells. B-cells synthesize organ-nonspecific and organspecific autoantibodies that are biomarkers for autoimmune diseases and play an important role in their immunopathogenesis. Anti-B-cell therapy that causes B-cell depletion in blood and target organs is effective in a wide range of IIRD. Its efficiency is determined by various mechanisms, such as suppression of pathogenic autoantibody synthesis; modulation of the function of B-cells (antigen presentation, cytokine synthesis, and costimulation), T-lymphocytes and dendritic cells. Further study of a strategy for targeted anti-B-cell therapy, mechanisms of action, and new targets is important for the progress of modern rheumatology to improve the treatment strategy of IIRD.

New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus erythematosus determined by a combination of QCM-D and DPI.

The mechanism of self-recognition of the autoantigen TROVE2, a common biomarker in autoimmune diseases, has been studied with a quartz crystal microbalance with dissipation monitoring (QCM-D) and dual polarization interferometry (DPI). The complementarity and remarkable analytical features of both techniques has allowed new insights into the onset of systemic lupus erythematosus (SLE) to be achieved at the molecular level. The in vitro study for SLE patients and healthy subjects suggests that anti-TROVE2 autoantibodies may undergo an antibody bipolar bridging. An epitope-paratope-specific binding initially occurs to activate a hidden Fc receptor in the TROVE2 tertiary structure. This bipolar mechanism may contribute to the pathogenic accumulation of anti-TROVE2 autoantibody immune complex in autoimmune disease. Furthermore, the specific calcium-dependent protein-protein bridges point out at how the TRIM21/TROVE2 association might occur, suggesting that the TROVE2 protein could stimulate the intracellular immune signaling via the TRIM21 PRY-SPRY domain. These findings may help to better understand the origins of the specificity and affinity of TROVE2 interactions, which might play a key role in the SLE pathogenesis. This manuscript gives one of the first practical applications of two novel functions (-df/dD and Δh/molec) for the analysis of the data provided by QCM-D and DPI. In addition, it is the first time that QCM-D has been used for mapping hidden Fc receptors as well as linear epitopes in a protein tertiary structure. Graphical abstract ᅟ.

Infectious biomarkers in autoimmune diseases - importance in personalised medicine

There is increasing evidence that bacteria may play important roles in the triggering of emerging diseases, including in autoimmune disease, attention deficit disorder (ADD), control of gut diseases, and depression. Bacterial presence in a susceptible host can be an important biomarker. In TB the presence of Mycobacterium tuberculosis is diagnostic of TB infection. With other members of the Mycobacterium species however, passive carriage or commensal colonisation may be ongoing and have no role in infection of the host. Atypical mycobacteria may be present in the normal individual and pose no risk, but the same organism may cause significant infections in the immune compromised host, in the elderly, and in children. Recent research into emerging infectious diseases suggests that over the last 40 years mycobacteria have evolved to exhibit novel biological mechanisms to avoid detection by the host and become “stealth pathogens”. The immune status of the host and the virulence of the infecting organism are therefore important considerations in diagnosing infectious diseases, and are challenges for the clinical laboratory. Close communication between the clinician and the medical laboratory staff are important requirements to ensure an optimal clinical response to complex interactions between bacteria and the host.

Exosome-encapsulated miR-6089 regulates inflammatory response via targeting TLR4.

Exosome-encapsulated microRNAs (miRNAs) have been identified as potential biomarkers in autoimmune diseases. However, little is known about the role of exosome-delivered miRNAs in rheumatoid arthritis (RA). In this study, we investigated the profile of specific exosomal miRNAs by microarray analysis of serum exosomes from three patients with RA and three healthy controls.Quantitative real-time PCR (qRT-PCR) was performed to validate the aberrantly expressed exosomal miRNAs. A total of 20 exosome-encapsulated miRNAs were identified to be differently expressed in the serum of patients with RA compared with controls. Interestingly, we found that exosome-encapsulated miR-6089 was significantly decreased after validation by qRT-PCR in serum exosomes from 76 patients with RA and 20 controls. Besides, miR-6089 could inhibit lipopolysaccharide (LPS)-induced cell proliferation and activation of macrophage-like THP-1 cells. TLR4 was a direct target for miR-6089. MiR-6089 regulated the generation of IL-6, IL-29, and TNF-α by targetedly controlling TLR4 signaling. In conclusion, exosome-encapsulated miR-6089 regulates LPS/TLR4-mediated inflammatory response, which may serve as a novel, promising biomarker in RA.

Analysis of the concentrations and size distributions of cell-free DNA in schizophrenia using fluorescence correlation spectroscopy

Cell-free DNA (cfDNA), which is primarily released following cell death, has been described and developed to serve as an effective biomarker in autoimmune diseases which may share the pathogenesis with schizophrenia. In this study, we hypothesized and explored whether the concentrations and size distributions of cfDNA are abnormal in schizophrenia. A total of 65 patients with schizophrenia (SZ), 29 patients with mood disorders (MD) and 62 matched healthy controls (HC) were included in the study. Fluorescence correlation spectroscopy was used to assay the molar concentrations and size distributions of cfDNA. Fluorometric quantification and quantitative real-time PCR (qPCR) were performed to verify the results. The cfDNA levels were approximately two-fold higher in the SZ group ((29 ± 15) nM) than in the healthy controls ((15 ± 9) nM; P-value = 0.00062), but the levels in patients with MD were not significantly different from those in the healthy controls ((17 ± 10) nM; P-value = 0.343). According to the size distribution analysis, cfDNA in schizophrenia patients was composed of shorter DNA molecules and showed an apoptosis-like distribution pattern. Our study shows the elevated levels and short sizes of cfDNA in schizophrenia patients, which provide direct evidences supporting increased apoptotic activity in the disease. cfDNA may be developed to serve as an auxiliary diagnostic marker for the disease in the future.

Epigenetics as biomarkers in autoimmune diseases

Autoimmune diseases are immune system disorders in which immune cells cannot distinguish self-antigens from foreign ones. The current criteria for autoimmune disease diagnosis are based on clinical manifestations and laboratory tests. However, none of these markers shows both high sensitivity and specificity. In addition, some autoimmune diseases, for example, systemic lupus erythematosus (SLE), are highly heterogeneous and often exhibit various manifestations. On the other hand, certain autoimmune diseases, such as Sjogren's syndrome versus SLE, share similar symptoms and autoantibodies, which also causes difficulties in diagnosis. Therefore, biomarkers that have both high sensitivity and high specificity for diagnosis, reflect disease activity and predict drug response are necessary. An increasing number of publications have proposed the abnormal epigenetic modifications as biomarkers of autoimmune diseases. Therefore, this review will comprehensively summarize the epigenetic progress in the pathogenesis of autoimmune disorders and unearth potential biomarkers that might be appropriate for disease diagnosis and prediction.

Single Cell Transcriptomics for Autoimmune Disorders

The interplay of genetic, immunological and environmental factors is the driving force towards autoimmunity and each of these branches of biological science is necessary to identify the cause and progress of autoimmune disorders. Differential transcript abundance as an effect of environmental or epigenetic modifications may directly regulate emergence while a sustained copy number increase may drive disease progression. A precise evaluation of these transcript level differences could be the key to understand the mechanism of development and progression of autoimmune diseases however it is imperative to quantitate the subtle changes at the highest resolution. This review summarizes the studies that have explored the importance of analyzing differential transcriptome at single cell resolution, further to emphasize the importance of this approach for enhanced understanding and to identify more sensitive and specific biomarkers for autoimmune diseases.

Lack of autoantibody induction by mercury exposure in artisanal gold mining settings in Colombia: Findings and a review of the epidemiology literature

Mercury (Hg) has been implicated as an immunotoxicant in experimental animal models, but its role in the induction of human autoimmunity remains unclear due to contradictory findings. Therefore, it has been claimed that it is important to examine other populations in order to clarify the role of Hg in these diseases. The aim of this study was to investigate whether occupational Hg exposure due to artisanal gold mining is associated with the prevalence of autoimmune biomarkers. A cross-sectional study was conducted comparing Hg-exposed gold miners (n = 164) with a control population (n = 127). Hair, blood, and 24-h urine samples were collected for measures of Hg levels, as well as of anti-nuclear antibodies (ANA) and rheumatoid factor (RF). Participants were clinically evaluated by a general practice physician, a rheumatologist, and a toxicologist. Statistically significant differences (p < 0.001) were found between Hg-exposed and non-exposed groups for all Hg biomarkers tested: blood (7.03 versus 2.46 µg Hg/L), urine (3.96 versus 1.48 µg Hg/g creatinine), and hair (0.79 versus 0.39 µg Hg/g). No difference was observed in ANA (cut-off titre of 1:80; PR = 0.93, 95% CI = 0.45–1.90) and RF (cut-off = 30 IU/mL; PR = 0.062, 95% CI = 0.03–1.08) status between the groups. In conclusion, the findings here do not support the hypothesis that Hg exposure due to artisanal gold mining activities had a significant impact on autoantibodies as biomarkers of autoimmune diseases. In a review context, the epidemiological findings were interpreted in light of the conflicting data in the literature about how Hg exposure was linked to development of autoantibodies. Validation of these findings in prospective studies is needed to firmly establish the role of Hg in development of autoimmunity in human populations.

SAT0220 Measurement of Serum Leucine-Rich Alpha-2 Glycoprotein, A Novel Disease Activity Biomarker in Rheumatoid Arthritis, for the Detection of Biologic-Associated Tuberculosis

BackgroundTuberculosis is considered to be a severe complication during biologic therapies in patients with rheumatoid arthritis (RA). Importantly, conventional inflammatory biomarkers such as C-reactive protein (CRP) and erythrocyte sedimentation rate...