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Frontiers in Immunology 2023Serum autoantibodies targeting the SSA/Ro proteins are a key component of the classification criteria for the diagnosis of Sjögren's syndrome (SS). Most patients' serum...
INTRODUCTION
Serum autoantibodies targeting the SSA/Ro proteins are a key component of the classification criteria for the diagnosis of Sjögren's syndrome (SS). Most patients' serum reacts with both Ro60 and Ro52 proteins. Here we compare the molecular and clinical characteristics of patients diagnosed with SS with anti-Ro52 in the presence or absence of anti-Ro60/La autoantibodies.
METHODS
A cross-sectional study was performed. Patients in the SS biobank at Westmead Hospital (Sydney, Australia) that were positive for anti-Ro52 were included and stratified based on the absence (isolated) or presence (combined) of anti-Ro60/La, measured by line immunoassay. We examined clinical associations and the serological and molecular characteristics of anti-Ro52 using ELISA and mass spectrometry in serological groups.
RESULTS
A total of 123 SS patients were included for study. SS patients with isolated anti-Ro52 (12%) identified a severe serological subset characterised by higher disease activity, vasculitis, pulmonary involvement, rheumatoid factor (RhF) and cryoglobulinaemia. Serum antibodies reacting with Ro52 in the isolated anti-Ro52 subset displayed less isotype switching, less immunoglobulin variable region subfamily usage and a lower degree of somatic hypermutation than the combined anti-Ro52 subset.
CONCLUSIONS
In our cohort of SS patients, isolated anti-Ro52 represents a severe subset of SS, and is associated with the presence of cryoglobulinaemia. We therefore provide clinical relevance to the stratification of SS patients by their sero-reactivities. It is possible that the autoantibody patterns may be immunological epiphenomena of the underlying disease process, and further work is required to unearth the mechanisms of the differential clinical phenotypes.
Topics: Humans; Sjogren's Syndrome; Cross-Sectional Studies; Cryoglobulinemia; Antibodies, Antinuclear; Autoantibodies
PubMed: 37006271
DOI: 10.3389/fimmu.2023.1115548 -
Turkish Journal of Medical Sciences Apr 2022Antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) have essential markers for the diagnosis of autoimmune hepatitis (AIH) and primary biliary...
BACKGROUND
Antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) have essential markers for the diagnosis of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). These autoantibodies are detecting different laboratory methods. In this study, we studied the diagnostic performance of used methods in detecting ANA and AMA.
METHODS
The autoantibody profiles of patients with AIH and PBC groups were analyzed with the indirect immunofluorescence test (IIF) and liver-specific antigens containing immunoblot test (IB).
RESULTS
There were 45 (87%) women in the study group and 8 (53%) women in the control group. The mean age of the patients was 50.5 ± 14.21 years old. The serum ALT and AST levels were higher in AIH, and ALP, GGT, and Ig M were higher in PBC. IIF test results among AIH/PBC groups; there was no difference in overall ANA positivity (p: 0.078). AMA was negative in all patients with AIH but positive in 83.3% of patients with PBC. IB test results among AIH/PBC groups; antibodies against PDGH, LKM-1, and Scl-70 were not observed in any patient with AIH/PBC. Except for M2 (p: 0.001) and M23E (p: 0.007) antibodies, there was no significant difference in antibodies between groups. Out of five PBC patients with negative AMA by IIF method, one was positive for AMA-M2, two were positive anti-gp210, and three were positive anti-M2-3E, but anti-sp100 was negative in all of them by the IB.
DISCUSSION
AIH/PBC has complex associations with different autoantibodies, and some of these antibodies are not readily detected by the IIF test. IB assays with a wide variety of liver-specific antigens may be helpful in the diagnosis (especially in patients with AMA negative PBC) and follow-up in AIH/PBC patients.
Topics: Humans; Female; Adult; Middle Aged; Male; Fluorescent Antibody Technique, Indirect; Liver Cirrhosis, Biliary; Autoantibodies; Hepatitis, Autoimmune; Immunologic Tests; Antibodies, Antinuclear
PubMed: 36422475
DOI: 10.55730/1300-0144.5512 -
Zhongguo Dang Dai Er Ke Za Zhi =... Aug 2022A girl aged 12 years and 2 months presented with recurrent abdominal pain and vomiting for more than 2 years and arthrodynia for 3 months. She was diagnosed with...
A girl aged 12 years and 2 months presented with recurrent abdominal pain and vomiting for more than 2 years and arthrodynia for 3 months. She was diagnosed with recurrent acute pancreatitis with unknown causes and had been admitted multiple times. Laboratory tests showed recurrent significant increases in fasting serum triglyceride, with elevated immunoglobulin and positive antinuclear antibody. The girl was improved after symptomatic supportive treatment. The girl developed arthrodynia with movement disorders 3 months before, and proteinuria, hematuria, and positive anti-double-stranded DNA antibody were observed. The renal biopsy was performed, and the pathological examination and immunofluorescence assay suggested diffuse lupus nephritis (type Ⅳ). She was finally diagnosed with systemic lupus erythematosus (SLE), lupus nephritis (type Ⅳ), and recurrent acute pancreatitis. Pancreatitis was suspected to be highly associated with SLE. She was treated with oral hydroxychloroquine sulfate and intravenous methylprednisolone sodium succinate and cyclophosphamide. Arthrodynia was partially relieved. She was then switched to oral prednisone acetate tablets. Intravenous cyclophosphamide and pump infusion of belimumab were regularly administered. Now she had improvement in arthrodynia and still presented with proteinuria and hematuria. It is concluded that recurrent acute pancreatitis may be the first clinical presentation of SLE. For pancreatitis with unknown causes, related immunological parameters should be tested, and symptoms of the other systems should be closely monitored to avoid delaying the diagnosis.
Topics: Abdominal Pain; Acute Disease; Antibodies, Antinuclear; Cyclophosphamide; Female; Hematuria; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Pancreatitis; Proteinuria; Triglycerides; Vomiting
PubMed: 36036131
DOI: 10.7499/j.issn.1008-8830.2203006 -
Journal of Translational Medicine Nov 2017Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in...
BACKGROUND
Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed.
METHODS
This was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables.
RESULTS
First, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity.
CONCLUSION
These results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.
Topics: Adult; Antibodies, Antinuclear; Autoantibodies; Cluster Analysis; Cross-Sectional Studies; Cytokines; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Young Adult
PubMed: 29178890
DOI: 10.1186/s12967-017-1345-y -
EBioMedicine Mar 2022Systemic Lupus Erythematosus (SLE) is a complex and heterogeneous autoimmune disease mediated by quantities of autoantibodies in which anti-double-stranded DNA...
BACKGROUND
Systemic Lupus Erythematosus (SLE) is a complex and heterogeneous autoimmune disease mediated by quantities of autoantibodies in which anti-double-stranded DNA (anti-dsDNA) antibodies are important. Besides, glycosylation is one of the most commonly post-translational modifications of antibodies. The association of anti-dsDNA antibodies glycosylation and SLE disease activity is still unknown.
METHODS
We enrolled 101 consecutive treatment-naïve SLE patients with positive anti-dsDNA antibodies from the Department of Rheumatology and Immunology at Ruijin Hospital, Shanghai, between 2017 and 2019. Serum samples were used in this study. We analysed the glycosylation of anti-dsDNA IgG and total IgG subclasses according to systemic lupus erythematosus disease activity index (SLEDAI) scores. Statistical analysis and machine learning were performed to assess the correlation between glycosylation of anti-dsDNA IgG and total IgG with disease activity.
FINDINGS
Serum samples from 86 patients could be detected with anti-dsDNA IgG glycopeptide and subclass of IgG glycoform. Cluster analysis showed that glycosylation of anti-dsDNA IgG and total IgG subclasses were different in SLE patients. Fucosylation, galactosylation, and sialylation levels of anti-dsDNA IgG1 were increased with SLEDAI scores (all p<0.05). The results of machine learning showed that all the glycoforms of anti-dsDNA IgG1 had better performance with lower standardised square error (SSE) than that of total IgG1, with anti-dsDNA IgG1 fucosylation level having the lowest SSE (0.009).
INTERPRETATION
Our study indicated that glycosylation of anti-dsDNA IgG was different from that of total IgG and fucosylation of anti-dsDNA IgG1 correlated best with SLE disease activity.
FUNDING
This work is supported by the National Key Research and Development Program of China (2018YFC0910303), National Natural Science Foundation of China (81801592, 82101876), Clinical Research Plan of SHDC (SHDC2020CR4011), Ruijin Hospital Youth Incubation Project (KY2021607) and Shanghai Pujiang Young Rheumatologists Training Program (SPROG202006).
Topics: Adolescent; Antibodies, Antinuclear; Autoantibodies; China; Glycosylation; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic
PubMed: 35182998
DOI: 10.1016/j.ebiom.2022.103883 -
Clinical Reviews in Allergy & Immunology Aug 2017Occurrence of autoantibodies (autoAbs) is a hallmark of autoimmune diseases, and the analysis thereof is an essential part in the diagnosis of organ-specific autoimmune... (Review)
Review
Occurrence of autoantibodies (autoAbs) is a hallmark of autoimmune diseases, and the analysis thereof is an essential part in the diagnosis of organ-specific autoimmune and systemic autoimmune rheumatic diseases (SARD), especially connective tissue diseases (CTDs). Due to the appearance of autoAb profiles in SARD patients and the complexity of the corresponding serological diagnosis, different diagnostic strategies have been suggested for appropriate autoAb testing. Thus, evolving assay techniques and the continuous discovery of novel autoantigens have greatly influenced the development of these strategies. Antinuclear antibody (ANA) analysis by indirect immunofluorescence (IIF) on tissue and later cellular substrates was one of the first tests introduced into clinical routine and is still an indispensable tool for CTD serology. Thus, screening for ANA by IIF is recommended to be followed by confirmatory testing of positive findings employing different assay techniques. Given the continuous growth in the demand for autoAb testing, IIF has been challenged as the standard method for ANA and other autoAb analyses due to lacking automation, standardization, modern data management, and human bias in IIF pattern interpretation. To address these limitations of autoAb testing, the CytoBead® technique has been introduced recently which enables automated interpretation of cell-based IIF and quantitative autoAb multiplexing by addressable microbead immunoassays in one reaction environment. Thus, autoAb screening and confirmatory testing can be combined for the first time. The present review discusses the history of autoAb assay techniques in this context and gives an overview and outlook of the recent progress in emerging technologies.
Topics: Antibodies, Antinuclear; Autoantibodies; Autoimmune Diseases; Autoimmunity; Biomarkers; Fluorescent Antibody Technique, Indirect; Humans
PubMed: 27368807
DOI: 10.1007/s12016-016-8574-3 -
Immunologic Research Mar 2013Systemic lupus erythematosus is a severe autoimmune disease that affects multiple organ systems resulting in diverse symptoms and outcomes. It is characterized by... (Review)
Review
Systemic lupus erythematosus is a severe autoimmune disease that affects multiple organ systems resulting in diverse symptoms and outcomes. It is characterized by antibody production to a variety of self-antigens, but it is specifically associated with those against anti-dsDNA. Anti-dsDNA antibodies are present before the onset of clinical disease and are associated with severe manifestations of lupus such as glomerulonephritis. Their levels fluctuate with changes in disease activity and, in combination with the levels of complement proteins C3 and C4, are strong indicators of disease flare and treatment response in patients with lupus. The decreased complement levels that are noted during flares of lupus activity are believed to be secondary to increased autoantibody production and immune complex formation that results in tissue damage; however, recent data suggest that complement activation can also drive development of these pathogenic autoantibodies. This review will explore the various roles of complement in the development and pathogenesis of anti-dsDNA antibodies.
Topics: Animals; Antibodies, Antinuclear; Complement System Proteins; Humans; Lupus Erythematosus, Systemic
PubMed: 22941560
DOI: 10.1007/s12026-012-8345-z -
Frontiers in Immunology 2022Although the prevalence of autoimmune hepatitis in first-degree relatives is small, the relationship between genetic markers, especially human leucocyte antigens (HLA),... (Review)
Review
Although the prevalence of autoimmune hepatitis in first-degree relatives is small, the relationship between genetic markers, especially human leucocyte antigens (HLA), and susceptibility to this disease, has been studied for over three decades. The genetic susceptibility to AIH is believed to be different in the two subtypes of the disease, AIH type 1 and AIH type 2. Type 1 AIH has anti-smooth muscle and anti-nuclear antibodies as its main markers, while those of type 2 AIH are the anti-liver/kidney microsome type 1 and anti-liver cytosol type 1 antibodies. The anti-soluble liver antigen/liver-pancreas antibodies, which, in addition to being present in both subtypes, mark an important number of patients without serological markers. Therefore, a third type of disease is questionable. The vast majority of immunogenetic studies compare the differences between the two main types and make no difference between which antibodies are present to define the subtype. This review seeks to analyze what was most important published in the AIH in this context, trying to relate the HLA alleles according to the AIH marker autoantibodies.
Topics: Humans; Hepatitis, Autoimmune; Genetic Predisposition to Disease; Autoantibodies; Antibodies, Antinuclear; Biomarkers
PubMed: 36311739
DOI: 10.3389/fimmu.2022.1032591 -
Immunological Reviews Jul 2012Systemic lupus erythematosus is an autoimmune disease characterized by antibodies that bind target autoantigens in multiple organs in the body. In peripheral organs,... (Review)
Review
Systemic lupus erythematosus is an autoimmune disease characterized by antibodies that bind target autoantigens in multiple organs in the body. In peripheral organs, immune complexes engage the complement cascade, recruiting blood-borne inflammatory cells and initiating tissue inflammation. Immune complex-mediated activation of Fc receptors on infiltrating blood-borne cells and tissue resident cells amplifies an inflammatory cascade with resulting damage to tissue function, ultimately leading to tissue destruction. This pathophysiology appears to explain tissue injury throughout the body, except in the central nervous system. This review addresses a paradigm we have developed for autoantibody-mediated brain damage. This paradigm suggests that antibody-mediated brain disease does not depend on immune complex formation but rather on antibody-mediated alterations in neuronal activation and survival. Moreover, antibodies only access brain tissue when blood-brain barrier integrity is impaired, leading to a lack of concurrence of brain disease and tissue injury in other organs. We discuss the implications of this model for lupus and for identifying other antibodies that may contribute to brain disease.
Topics: Amygdala; Animals; Antibodies, Antinuclear; Antibody Specificity; Autoantibodies; Blood-Brain Barrier; Brain; Brain Diseases; Hippocampus; Humans; Lupus Erythematosus, Systemic; Models, Immunological; Neurons; Peptides; Protein Binding; Receptors, N-Methyl-D-Aspartate
PubMed: 22725954
DOI: 10.1111/j.1600-065X.2012.01137.x -
Clinical and Vaccine Immunology : CVI Dec 2017The presence of antinuclear antibodies (ANAs) is a hallmark of a number of systemic autoimmune rheumatic diseases, and testing is usually performed as part of the... (Review)
Review
The presence of antinuclear antibodies (ANAs) is a hallmark of a number of systemic autoimmune rheumatic diseases, and testing is usually performed as part of the initial diagnostic workup when suspicion of an underlying autoimmune disorder is high. The indirect immunofluorescence antibody (IFA) technique is the preferred method for detecting ANAs, as it demonstrates binding to specific intracellular structures within the cells, resulting in a number of staining patterns that are usually categorized based on the cellular components recognized and the degree of binding, as reflected by the fluorescence intensity or titer. As a screening tool, the ANA patterns can guide confirmatory testing useful in elucidating a specific clinical diagnosis or prognosis. However, routine use of ANA IFA testing as a global screening test is hampered by its labor-intensiveness, subjectivity, and limited diagnostic specificity, among other factors. This review focuses on current efforts to standardize the nomenclature of ANA patterns and on alternative methods for ANA determination, as well as on recent advances in image-based computer algorithms to automate IFA testing in clinical laboratories.
Topics: Antibodies, Antinuclear; Autoimmune Diseases; Humans; Immunoassay
PubMed: 29021301
DOI: 10.1128/CVI.00270-17