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Frontiers in Immunology 2018Autoantibody production occurs in juvenile idiopathic arthritis (JIA) and numerous other autoimmune diseases. In some conditions, the autoantibodies are clearly... (Review)
Review
Autoantibody production occurs in juvenile idiopathic arthritis (JIA) and numerous other autoimmune diseases. In some conditions, the autoantibodies are clearly pathogenic, whereas in others the roles are less defined. Here we review various autoantibodies associated with JIA, with a particular focus on antinuclear antibodies and antibodies recognizing citrullinated self-antigens. We explore potential mechanisms that lead to the development of autoantibodies and the use of autoantibody testing in diagnosis and prognosis. Finally, we compare and contrast JIA-associated autoantibodies with those found in adults with rheumatoid arthritis (RA).
Topics: Antibodies, Antinuclear; Antigen-Antibody Complex; Arthritis, Juvenile; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Autoimmunity; Biomarkers; Humans; Immune Tolerance; Molecular Mimicry; Prognosis; Protein Binding; Rheumatoid Factor
PubMed: 30693002
DOI: 10.3389/fimmu.2018.03168 -
Allergy Aug 2022Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this...
BACKGROUND
Several autoimmune features occur during coronavirus disease 2019 (COVID-19), with possible implications for disease course, immunity, and autoimmune pathology. In this study, we longitudinally screened for clinically relevant systemic autoantibodies to assess their prevalence, temporal trajectory, and association with immunity, comorbidities, and severity of COVID-19.
METHODS
We performed highly sensitive indirect immunofluorescence assays to detect antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA), along with serum proteomics and virome-wide serological profiling in a multicentric cohort of 175 COVID-19 patients followed up to 1 year after infection, eleven vaccinated individuals, and 41 unexposed controls.
RESULTS
Compared with healthy controls, similar prevalence and patterns of ANA were present in patients during acute COVID-19 and recovery. However, the paired analysis revealed a subgroup of patients with transient presence of certain ANA patterns during acute COVID-19. Furthermore, patients with severe COVID-19 exhibited a high prevalence of ANCA during acute disease. These autoantibodies were quantitatively associated with higher SARS-CoV-2-specific antibody titers in COVID-19 patients and in vaccinated individuals, thus linking autoantibody production to increased antigen-specific humoral responses. Notably, the qualitative breadth of antibodies cross-reactive with other coronaviruses was comparable in ANA-positive and ANA-negative individuals during acute COVID-19. In autoantibody-positive patients, multiparametric characterization demonstrated an inflammatory signature during acute COVID-19 and alterations of the B-cell compartment after recovery.
CONCLUSION
Highly sensitive indirect immunofluorescence assays revealed transient autoantibody production during acute SARS-CoV-2 infection, while the presence of autoantibodies in COVID-19 patients correlated with increased antiviral humoral immune responses and inflammatory immune signatures.
Topics: Antibodies, Antineutrophil Cytoplasmic; Antibodies, Antinuclear; Antiviral Agents; Autoantibodies; COVID-19; Humans; Immunity, Humoral; SARS-CoV-2
PubMed: 35364615
DOI: 10.1111/all.15302 -
Lupus Science & Medicine 2020Diagnosis of SLE in early stages is challenging due to the heterogeneous nature of presenting symptoms and the poor performance metrics of the screening ANA test. Even... (Review)
Review
Diagnosis of SLE in early stages is challenging due to the heterogeneous nature of presenting symptoms and the poor performance metrics of the screening ANA test. Even the more specific double-stranded DNA autoantibody has relatively low predictive value in early disease. A consequence is delayed referral, with the likelihood that some patients have progression of disease prior to specialist evaluation. Tests that might fill this diagnostic gap are therefore needed. The AVISE Connective Tissue Disease Test that uses a multiplex approach to detect autoantibodies and cell-bound complement products has shown utility in distinguishing SLE from other rheumatological conditions. Whether it might be useful in early disease stages to predict progression is addressed in a recent study by Liang and colleagues, who tested clinic patients who had non-specific findings with the objective of determining whether AVISE could predict onset of SLE. While this test provided more useful prognostic information than other available diagnostics, it had relatively low sensitivity, suggesting that significant numbers of patients with preclinical SLE would be missed by this screening. The need remains for development of diagnostics with robust sensitivity and specificity in early disease that would also deliver prognostic information about risk for SLE. Such tests would have great value as a tool for primary providers to more efficiently triage ANA-positive patients for appropriate specialty evaluation.
Topics: Antibodies, Antinuclear; Autoantibodies; DNA; Disease Progression; Humans; Lupus Erythematosus, Systemic; Mass Screening; Predictive Value of Tests; Prognosis; Sensitivity and Specificity
PubMed: 32095251
DOI: 10.1136/lupus-2020-000384 -
Translational Research : the Journal of... Jul 2022Lupus nephritis (LN) develops in more than a third of all systemic lupus erythematosus (SLE) patients and is the strongest predictor of morbidity and mortality.... (Review)
Review
Lupus nephritis (LN) develops in more than a third of all systemic lupus erythematosus (SLE) patients and is the strongest predictor of morbidity and mortality. Increased circulating levels of type I interferon (IFN I) and anti-double stranded DNA (anti-dsDNA) and anti-RNA binding protein (anti-RNP) antibodies lead to increased glomerular injury via leukocyte activation and glomerular infiltration. Uncontrolled Toll-like receptor (TLR) signaling in leukocytes results in increased production of IFN I and anti-dsDNA antibodies. ITGAM gene codes for integrin CD11b, the α-chain of integrin heterodimer CD11b/CD18, that is highly expressed in leukocytes and modulates TLR-dependent pro-inflammatory signaling. Three nonsynonymous SNPs in the ITGAM gene strongly correlate with increased risk for SLE and LN and with IFN I levels. Here we review the literature on the role of CD11b on leukocytes in LN. We also incorporate conclusions from several recent studies that show that these ITGAM SNPs result in a CD11b protein that is less able to suppress TLR-dependent pro-inflammatory pathways in leukocytes, that activation of CD11b via novel small molecule agonists suppresses TLR-dependent pathways, including reductions in circulating levels of IFN I and anti-dsDNA antibodies, and that CD11b activation reduces LN in model systems. Recent data strongly suggest that integrin CD11b is an exciting new therapeutic target in SLE and LN and that allosteric activation of CD11b is a novel therapeutic paradigm for effectively treating such autoimmune diseases.
Topics: Antibodies, Antinuclear; Humans; Interferon Type I; Lupus Erythematosus, Systemic; Lupus Nephritis; Toll-Like Receptors
PubMed: 35288363
DOI: 10.1016/j.trsl.2022.03.001 -
Clinical Reviews in Allergy & Immunology Oct 2022Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse serological autoantibodies. Anti-dsDNA antibodies are involved in multiple organ damage, especially the kidney, skin, and central nervous system. Anti-dsDNA antibodies play a pivotal role in SLE, and researchers have developed therapeutic strategies targeting these antibodies. Approaches to reduce anti-dsDNA antibodies via B cell targeted biologics against B cell surface antigens, B cell survival factors, or Bruton's tyrosine kinase have effectively eliminated B cells. However, their non-specific depletion hampers normal immune system functioning and limits the therapeutic benefits. Thus, scientists have attempted anti-dsDNA antibodies or lupus-specific strategies, such as the immature dendritic cell vaccine and immunoadsorption. Recently, synthetic mimic peptides (hCDR1, pCONs, DWEYS, FISLE-412, and ALW) that directly block anti-dsDNA autoantibodies have attracted attention, which could ameliorate lupus, decrease the serological autoantibody titer, reduce the deposition of renal autoantibodies, and improve pathological performance. These potent small peptide molecules are well tolerated, non-toxic, and non-immunogenic, which have demonstrated a benign safety profile and are expected to be hopeful candidates for SLE management. In this review, we clarify the role of anti-dsDNA antibodies in SLE, mainly focus on the current strategies targeting anti-dsDNA antibodies, and discuss their potential clinical value.
Topics: Antibodies, Antinuclear; Autoantibodies; B-Lymphocytes; Humans; Lupus Erythematosus, Systemic; Peptides
PubMed: 34542806
DOI: 10.1007/s12016-021-08898-7 -
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 -
Arthritis Research & Therapy Jul 2017Testing for the presence of antinuclear antibodies (ANAs) is a key step in the diagnosis of systemic lupus erythematosus (SLE) and other systemic autoimmune rheumatic... (Review)
Review
Testing for the presence of antinuclear antibodies (ANAs) is a key step in the diagnosis of systemic lupus erythematosus (SLE) and other systemic autoimmune rheumatic diseases (SARD). The standard slide-based indirect immunofluorescence (IIF) test is widely used, but is limited by a relative lack of specificity for SLE and not all SARD-ANAs are detected. Alternative immunoassays that might offer enhanced diagnostic and prognostic information have evolved, and some of these have entered clinical practice. This review summarizes the current state of ANA testing and multiplex techniques for detecting other autoantibodies, the possibility of point-of-care testing, and approaches for applications in early disease stages.
Topics: Antibodies, Antinuclear; Autoantibodies; Humans; Immunoassay; Rheumatic Diseases
PubMed: 28738887
DOI: 10.1186/s13075-017-1380-3 -
Frontiers in Immunology 2021TRIM21 (Ro52/SSA1) is an E3 ubiquitin ligase with key roles in immune host defence, signal transduction, and possibly cell cycle regulation. It is also an autoantibody... (Review)
Review
TRIM21 (Ro52/SSA1) is an E3 ubiquitin ligase with key roles in immune host defence, signal transduction, and possibly cell cycle regulation. It is also an autoantibody target in Sjögren's syndrome, systemic lupus erythematosus, and other rheumatic autoimmune diseases. Here, we summarise the structure and function of this enzyme, its roles in innate immunity, adaptive immunity and cellular homeostasis, the pathogenesis of autoimmunity against TRIM21, and the potential impacts of autoantibodies to this intracellular protein.
Topics: Animals; Antibodies, Antinuclear; Autoimmune Diseases; Autoimmunity; Epitopes; Humans; Immunity, Innate; Protein Conformation; Ribonucleoproteins; Signal Transduction; Structure-Activity Relationship
PubMed: 34552597
DOI: 10.3389/fimmu.2021.738473 -
Clinical Rheumatology Jun 2022Behçet's syndrome (BS) is a multi-systemic vasculitis characterized by recurrent oral ulcers, genital ulcers, ocular lesions, and other systemic manifestations. As...
BACKGROUND
Behçet's syndrome (BS) is a multi-systemic vasculitis characterized by recurrent oral ulcers, genital ulcers, ocular lesions, and other systemic manifestations. As there is no laboratory diagnostics of BS, the diagnosis is mainly clinical.
OBJECTIVE
To investigate the utility of the autoantibody against tubulin-α-1c in diagnosis of BS and its clinical significance.
METHODS
Sixty BS patients and sixty healthy controls were enrolled in this study. We assessed all patients by Behçet disease current activity form (BDCAF), routine laboratory investigations, and immunological markers (ANA, anti-DNA, ANCA). Anti-endothelial cell antibodies (AECA) and anti-tubulin-alpha-1c antibodies were performed for all participants.
RESULTS
Regarding duration of illness, Birmingham Vasculitis Activity Score (BVAS), and BDCAF, the mean value was 4.77 ± 4.239, 19.80 ± 10.020, and 9.52 ± 5.476, respectively. On comparing laboratory investigations, there was only significant increase in anti-tubulin-alpha-1c antibody in BS patients compared to healthy controls. Regarding AECA, there was no any significant correlation except with CRP. Anti-tubulin-alpha-1c detected significant direct correlation with the presence of posterior uveitis, panuveitis, and venous thrombosis as well as BVAS, C4, and protein/creatinine ratio. Regarding diagnostic performance of both AECA and anti-tubulin-alpha-1c, the cutoff value of AECA for diagnosis was 27.250, with sensitivity and specificity of 93.3% and 96.7%, respectively. The cutoff value of the anti-tubulin-alpha-1c for diagnosis was 22.300, with sensitivity and specificity of 100% and 96.7% respectively.
CONCLUSION
Anti-tubulin-α-1c antibodies are of diagnostic value in BS and are indicative of activity with 100% sensitivity and 96.7% specificity. Key Points • There is lack of specific laboratory, radiological, or histological diagnostics for Behcet syndrome. • We aimed to evaluate the significance of tubulin-α-1c autoantibody in diagnosis of Behcet syndrome. • There is elevation of tubulin-α-1c autoantibody with sensitivity and specificity of 100% and 96.7%, respectively.
Topics: Antibodies, Antinuclear; Behcet Syndrome; Biomarkers; Humans; Sensitivity and Specificity; Tubulin
PubMed: 35128589
DOI: 10.1007/s10067-021-06025-7 -
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