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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 -
Scientific Reports Jul 2022Systemic sclerosis (SSc) is characterized by the presence of SSc-specific or SSc-associated antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA),...
Systemic sclerosis (SSc) is characterized by the presence of SSc-specific or SSc-associated antibodies (SSc-Abs): anti-topoisomerase I (ATA), anti-centromere (ACA), anti-RNA polymerase III (ARA), anti-U3RNP (U3RNP), anti-U1RNP (U1RNP), anti-PmScl (PmScl), anti-Ku (Ku) and anti-Th/To (Th/To), each being associated with specific clinical features and prognosis. The detection of more than one SSc-Abs in SSc patients is rare and only few data about these patients' clinical phenotype is available. The aim of our study was to evaluate the frequency and the disease's features associated with the presence of > 1 SSc-Abs positivity in a large cohort of SSc patients. The autoantibody profiles of 2799 SSc patients from February 2001 to June 2017 were retrospectively reviewed. Patients with > 1 SSc-Abs were identified. Clinical features were collected and compared to a large historical cohort of SSc patients with single SSc-Ab positivity. SSc patients were excluded if previously treated with rituximab, intravenous immunoglobulins or stem cell transplantation. Non-parametric tests were used for statistical analysis. Nearly 5% of SSc patients from our cohort had ≥ 2 autoantibody positivity, and 2.3% (n = 72) had ≥ 2 SSc-Abs positivity. Th e most common combination was U1RNP and ATA (35%). These patients were younger than patients with single autoantibody positivity and showed more commonly a diffuse cutaneous SSc form. They also had higher rates of overlap features compared to ATA patients. Other combinations included U1RNP and ACA (13%), ATA and ACA (7%) and U1RNP and PmScl (5%). In our study we observed that, while infrequently, SSc patients can present with a combination of two SSc-Abs and that the double positivity can influence their clinical phenotype compared to patients with single SSc-Ab positivity. The importance of re-testing SSc-Abs in patients with changing clinical phenotypes was also highlighted, as this may confer a differing risk stratification.
Topics: Antibodies, Antinuclear; Autoantibodies; Humans; Phenotype; Retrospective Studies; Scleroderma, Localized; Scleroderma, Systemic
PubMed: 35780179
DOI: 10.1038/s41598-022-15062-4 -
PloS One 2017Recent studies suggest antinuclear antibodies (ANA) may be related to mortality risk, but evidence is sparse and inconclusive. Thus, we investigated ANA associations...
OBJECTIVE
Recent studies suggest antinuclear antibodies (ANA) may be related to mortality risk, but evidence is sparse and inconclusive. Thus, we investigated ANA associations with all-cause and cause-specific mortality in U.S. adults.
METHODS
Our sample included 3357 adults (ages ≥20 years) from the 1999-2004 National Health and Nutrition Examination Survey with ANA measurements (1:80 dilution) and mortality data through 2011 (median follow-up: 9.4 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) via weighted Cox regression to assess ANA associations with mortality from all causes, cardiovascular disease (CVD), and cancer. Models adjusted for age, sex, race/ethnicity, education, and obesity. Analyses examined mortality in the full sample and in subgroups based on self-reported histories of CVD and cancer, both overall and stratified by sex and age at enrollment.
RESULTS
Overall, ANA were not strongly associated with death from all causes (HR: 1.13; CI: 0.79, 1.60), from CVD (HR: 1.60; CI: 0.80, 3.20), or from cancer (HR: 1.58; CI: 0.75, 3.33), though all three HR estimates exceeded 1. In the subgroup with a history of cancer, ANA were associated with elevated all-cause mortality in men (HR: 2.28; CI: 1.01, 5.14) and in participants who enrolled at age ≥75 years (HR: 1.99; CI: 1.04, 3.80).
CONCLUSION
These findings suggest that ANA are not strongly associated with mortality in the general population. Longitudinal studies with repeated assessments are needed to understand the temporal relationship between ANA, aging-associated diseases, and mortality.
Topics: Adult; Aged; Antibodies, Antinuclear; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Neoplasms; Nutrition Surveys; Obesity; Proportional Hazards Models; Risk Factors
PubMed: 29016697
DOI: 10.1371/journal.pone.0185977 -
Jornal Brasileiro de Pneumologia :... 2013The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can... (Review)
Review
The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.
Topics: Antibodies, Antinuclear; Autoantibodies; Autoimmune Diseases; Biopsy; Connective Tissue Diseases; Diagnosis, Differential; Humans; Lung Diseases, Interstitial; Prognosis
PubMed: 24473767
DOI: 10.1590/S1806-37132013000600012 -
Annals of the Rheumatic Diseases Sep 1991
Review
Topics: Antibodies, Antinuclear; Arthritis, Juvenile; Child; Histones; Humans; Immunoblotting; Immunoglobulin G; Uveitis, Anterior
PubMed: 1929579
DOI: 10.1136/ard.50.9.595 -
Asian Pacific Journal of Allergy and... Dec 2021Juvenile systemic lupus erythematosus (JSLE) and adult SLE (ASLE) patients present with different clinical manifestations, but it is unknown if there are differences in...
BACKGROUND
Juvenile systemic lupus erythematosus (JSLE) and adult SLE (ASLE) patients present with different clinical manifestations, but it is unknown if there are differences in their antinuclear autoantibody (ANA) profiles or if staining patterns are associated with specific autoantibodies and clinical manifestations.
OBJECTIVE
To determine whether distinct types and numbers of ANA-staining patterns are associated with specific autoantibodies and clinical manifestations in JSLE and ASLE patients.
METHODS
A retrospective study was performed in Thai children (n = 146) and adults (n = 180) diagnosed with SLE using the Systemic Lupus International Collaborating Clinics classification criteria.
RESULTS
JSLE patients with a homogeneous pattern of staining and anti-dsDNA or anti-nucleosome antibodies in serum, developed renal involvement, leukopenia and acute/subacute cutaneous LE. Coarse speckled pattern with anti-RNP or anti-Sm showed thrombocytopenia and renal involvement in JSLE patients, but leukopenia in both groups. JSLE patients with fine-coarse speckled pattern and anti-RNP, anti-Sm, anti-Ro-52 or anti-SSA developed leukopenia, thrombocytopenia and renal involvement, whilst hemolytic anemia and serositis were commonly found in those with anti-Ro-52. Median SLEDAI score was higher in JSLE than ASLE patients.
CONCLUSIONS
Detailed ANA-staining patterns with specific autoantibodies show particular clinical manifestations and hence prompt further clinical investigations in both JSLE and ASLE patients. Therefore, this study demonstrates that distinct patterns of ANA staining and specific autoantibodies are clinically important in both children and adults with SLE.
Topics: Adult; Antibodies, Antinuclear; Autoantibodies; Child; Humans; Lupus Erythematosus, Systemic; Retrospective Studies
PubMed: 31012595
DOI: 10.12932/AP-211218-0465 -
International Journal of Cancer Aug 2022Annexin A2 (ANXA2) is widely used as a marker in a variety of tumors. By regulating multiple signal pathways, ANXA2 promotes the epithelial-mesenchymal transition, which... (Review)
Review
Annexin A2 (ANXA2) is widely used as a marker in a variety of tumors. By regulating multiple signal pathways, ANXA2 promotes the epithelial-mesenchymal transition, which can cause tumorigenesis and accelerate thymus degeneration. The elevated ANXA2 heterotetramer facilitates the production of plasmin, which participates in pathophysiologic processes such as tumor cell invasion and metastasis, bleeding diseases, angiogenesis, inducing the expression of inflammatory factors. In addition, the ANXA2 on the cell membrane mediates immune response via its interaction with surface proteins of pathogens, C1q, toll-like receptor 2, anti-dsDNA antibodies and immunoglobulins. Nuclear ANXA2 plays a role as part of a primer recognition protein complex that enhances DNA synthesis and cells proliferation by acting on the G1-S phase of the cell. ANXA2 reduction leads to the inhibition of invasion and metastasis in multiple tumor cells, bleeding complications in acute promyelocytic leukemia, retinal angiogenesis, autoimmunity response and tumor drug resistance. In this review, we provide an update on the pathological effects of ANXA2 in both tumorigenesis and the immune response. We highlight ANXA2 as a critical protein in numerous malignancies and the immune host response.
Topics: Annexin A2; Antibodies, Antinuclear; Cell Line, Tumor; Cell Transformation, Neoplastic; Epithelial-Mesenchymal Transition; Humans; Immunity; Neoplasms; Neovascularization, Pathologic
PubMed: 35474212
DOI: 10.1002/ijc.34048 -
Autoimmunity Reviews Dec 2023Anti-dsDNA autoantibodies are listed as one of the classification criteria for systemic lupus erythematosus (SLE) and are relatively effective indicators for monitoring... (Review)
Review
Anti-dsDNA autoantibodies are listed as one of the classification criteria for systemic lupus erythematosus (SLE) and are relatively effective indicators for monitoring disease activity and treatment response. Therefore, clinicians rely on them to diagnose and adjust medication and treatment strategies for SLE patients. However, the use of anti-dsDNA antibodies is not free from controversy. Part of this controversy stems from the fact that anti-dsDNA antibodies are found in several disorders, besides SLE. In addition to this, anti-dsDNA antibodies are a heterogeneous group of antibodies, and their determination still lacks proper standardization. Moreover, anti-dsDNA testing specificity and diagnostic performance change depending on the population under study. These and other issues result in inconsistency and encumber the clinical use of anti-dsDNA antibodies. A panel of medical laboratory and clinical experts on SLE discussed such issues based on their clinical experience in a first meeting, establishing a series of recommendations. The proceedings of this first meeting, plus an exhaustive review of the literature, were used to compose a paper draft. The panel subsequently discussed and refined this draft in a second meeting, the result of which is this paper. This document is relevant to clinical laboratories as it guides to improving diagnosis and monitoring of SLE. Simultaneously, it will help laboratories compile more informative reports, not limited to a mere number. It is also relevant to clinical doctors who wish to better understand laboratory methods so that they can do a more efficient, better-aimed laboratory test ordering.
Topics: Humans; Autoantibodies; Follow-Up Studies; Lupus Erythematosus, Systemic; Antibodies, Antinuclear
PubMed: 37967782
DOI: 10.1016/j.autrev.2023.103479 -
Frontiers in Immunology 2023Recent studies report high-titer anti-dense fine speckled 70 (DFS70) autoantibodies in persons with inflammatory conditions, but the clinical significance remains...
OBJECTIVE
Recent studies report high-titer anti-dense fine speckled 70 (DFS70) autoantibodies in persons with inflammatory conditions, but the clinical significance remains unclear. Our goals were to estimate anti-DFS70 autoantibody prevalence, identify correlates, and assess time trends.
METHODS
Serum antinuclear antibodies (ANA) were measured by indirect immunofluorescence assay on HEp-2 cells in 13,519 participants ≥12 years old from three time periods (1988-1991, 1999-2004, 2011-2012) of the National Health and Nutrition Examination Survey. ANA-positive participants with dense fine speckled staining were evaluated for anti-DFS70 antibodies by enzyme-linked immunosorbent assay. We used logistic models adjusted for survey-design variables to estimate period-specific anti-DFS70 antibody prevalence in the US, and we further adjusted for sex, age, and race/ethnicity to identify correlates and assess time trends.
RESULTS
Women were more likely than men (odds ratio (OR)=2.97), black persons were less likely than white persons (OR=0.60), and active smokers were less likely than nonsmokers (OR=0.28) to have anti-DFS70 antibodies. The prevalence of anti-DFS70 antibodies increased from 1.6% in 1988-1991 to 2.5% in 1999-2004 to 4.0% in 2011-2012, which corresponds to 3.2 million, 5.8 million, and 10.4 million seropositive individuals, respectively. This increasing time trend in the US population (P<0.0001) was modified in some subgroups and was not explained by concurrent changes in tobacco smoke exposure. Some, but not all, anti-DFS70 antibody correlates and time trends resembled those reported for total ANA.
CONCLUSION
More research is needed to elucidate anti-DFS70 antibody triggers, their pathologic or potentially protective influences on disease, and their possible clinical implications.
Topics: Female; Humans; Male; Adaptor Proteins, Signal Transducing; Antibodies, Antinuclear; Autoantibodies; Nutrition Surveys; Prevalence; United States
PubMed: 37426660
DOI: 10.3389/fimmu.2023.1186439 -
Scandinavian Journal of Immunology 2004Histopathology of the kidney and clinical presentation are critical factors in the diagnosis of immune-mediated glomerulonephritis (GN). The histological manifestations... (Review)
Review
Histopathology of the kidney and clinical presentation are critical factors in the diagnosis of immune-mediated glomerulonephritis (GN). The histological manifestations of glomerular injury are shared by multiple underlying mechanisms. Work from our laboratory and from other investigators shows that antinuclear, antihistone or anti-dsDNA antibodies are neither required nor sufficient for development of lupus GN. In addition, antibody to dsDNA can be generated by mechanisms other than loss of tolerance to chromatin. Genetic analyses demonstrate that although there is some interaction between autoantibody production and renal disease, the phenotypes are regulated by distinct genetic intervals. Furthermore, renal failure is not an essential outcome of the immune-complex deposition and proliferative lupus GN. These data are also supported by published studies from systemic lupus erythematosus (SLE) patients. The immune regulation of lupus GN is distinct from other organ-specific diseases and not influenced by CD25(+) or NK1.1(+) regulatory T cells. Thus, fatal GN may depend upon a kidney-reactive T-cell response that, in turn, may be regulated by gender and intrinsic end-organ factors. The data discussed in this review call for a re-evaluation of the current paradigms for pathogenesis of SLE. An interactive model separating autoimmunity from end-organ susceptibility for the pathogenesis of SLE is proposed.
Topics: Animals; Antibodies, Antinuclear; Autoimmunity; DNA; Female; Humans; Lupus Nephritis; Male; Mice; Mice, Inbred Strains
PubMed: 15238073
DOI: 10.1111/j.0300-9475.2004.01463.x