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European Review For Medical and... Dec 2020The pathogenesis of primary hypertension (HT) is still not completely clear, although autoimmunity has been implicated in recent years. Carbonic anhydrase (CA) is an...
OBJECTIVE
The pathogenesis of primary hypertension (HT) is still not completely clear, although autoimmunity has been implicated in recent years. Carbonic anhydrase (CA) is an enzyme involved in a number of important metabolic processes. CA I and II autoantibodies have been linked to various autoimmune diseases. However, CA I and II autoantibody levels in primary HT have not been previously investigated. The purpose of this study was, therefore, to investigate levels of CA I and II autoantibodies in primary HT.
PATIENTS AND METHODS
Fifty-six patients newly diagnosed with primary HT and 33 healthy individuals were included in the study. Twenty-four-hour ambulatory blood pressure monitoring was performed following office controls. Blood specimens were collected under appropriate conditions for CA I and II autoantibody level investigation and biochemical tests. Urine sodium and protein excretion were measured after 24 h. Demographic and biochemical parameters and CA I and II autoantibody levels were then compared between the patient and healthy groups.
RESULTS
CA II autoantibody and uric acid levels were significantly higher in the hypertensive group than in the control group (p=0.005, and p<0.001, respectively). CA II autoantibody (exp ß: 79.06 CI: 4.44-1407.02) (p=0.003) and uric acid elevation (exp ß: 2.10 CI: 1.31- 3.34) (p=0.002) were identified as independent predictors of HT development at logistic regression analysis.
CONCLUSIONS
CA II autoantibody levels were higher in hypertensive patients, and this elevation is an independent predictor of HT development.
Topics: Autoantibodies; Carbonic Anhydrase I; Carbonic Anhydrase II; Female; Humans; Hypertension; Male; Middle Aged
PubMed: 33378031
DOI: 10.26355/eurrev_202012_24183 -
International Journal of Molecular... Dec 2023We investigated the impact of synthetic nucleic acid antigens on the autoantibody profiles in patients with localized scleroderma, an autoimmune skin disease. Anti-DNA...
We investigated the impact of synthetic nucleic acid antigens on the autoantibody profiles in patients with localized scleroderma, an autoimmune skin disease. Anti-DNA antibodies, including double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA), are common among autoimmune diseases, such as systemic lupus erythematosus and localized scleroderma. Based on recent studies, we hypothesized that the sequence of nucleic acid antigens has an impact on the autoimmune reactions in localized scleroderma. To test our hypothesis, we synthesized a panel of DNA and RNA antigens and used them for autoantibody profiling of 70 children with localized scleroderma compared with the healthy controls and patients with pediatric systemic lupus erythematosus (as a disease control). Among the tested antigens, dsD4, which contains the sequence of the human oncogene , showed a particularly strong presence in localized scleroderma but not systemic lupus erythematosus. Disease activity in patients was significantly associated with dsD4 autoantibody levels. We confirmed this result in vivo by using a bleomycin-induced mouse model of localized scleroderma. When administered intraperitoneally, dsD4 promoted an active polyclonal response in the mouse model. Our study highlights sequence specificity for nucleic acid antigens in localized scleroderma that could potentially lead to developing novel early-stage diagnostic tools.
Topics: Animals; Mice; Humans; Child; Scleroderma, Localized; Autoimmune Diseases; Lupus Erythematosus, Systemic; Autoantibodies; Antigens; DNA; DNA, Single-Stranded
PubMed: 38139335
DOI: 10.3390/ijms242417507 -
Frontiers in Immunology 2022
Topics: Humans; Autoantibodies; RNA; Arthritis, Rheumatoid; Rheumatoid Factor
PubMed: 36341462
DOI: 10.3389/fimmu.2022.1037843 -
Scientific Reports Jul 2021Autoimmune retinopathy (AIR) is a rare immune-mediated inflammation of the retina. The autoantibodies against retinal proteins and glycolytic enzymes were reported to...
Autoimmune retinopathy (AIR) is a rare immune-mediated inflammation of the retina. The autoantibodies against retinal proteins and glycolytic enzymes were reported to be involved in the pathogenesis. This retrospective cohort study assessed the antiretinal autoantibody profiles and their association with clinical outcomes of AIR patients in Thailand. We included 44 patients, 75% were females, with the overall median age of onset of 48 (17-74, IQR 40-55.5) years. Common clinical presentations were nyctalopia (65.9%), blurred vision (52.3%), constricted visual field (43.2%), and nonrecordable electroretinography (65.9%). Underlying malignancy and autoimmune diseases were found in 2 and 12 female patients, respectively. We found 41 autoantibodies, with anti-α-enolase (65.9%) showing the highest prevalence, followed by anti-CAII (43.2%), anti-aldolase (40.9%), and anti-GAPDH (36.4%). Anti-aldolase was associated with male gender (P = 0.012, OR 7.11, 95% CI 1.54-32.91). Anti-CAII showed significant association with age of onset (P = 0.025, 95% CI - 17.28 to - 1.24), while anti-α-enolase (P = 0.002, OR 4.37, 95% CI 1.83-10.37) and anti-GAPDH (P = 0.001, OR 1.87, 95% CI 1.32-2.64) were significantly associated with nonrecordable electroretinography. Association between the antibody profiles and clinical outcomes may be used to direct and adjust the treatment plans and provide insights in the pathogenesis of AIR.
Topics: Adolescent; Adult; Aged; Autoantibodies; Autoantigens; Autoimmune Diseases; Autoimmunity; Biomarkers; Disease Susceptibility; Electroretinography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Retina; Retinal Diseases; Retrospective Studies; Young Adult
PubMed: 34294798
DOI: 10.1038/s41598-021-94377-0 -
Seizure Oct 2016The growing recognition of epilepsies and encephalopathies associated with autoantibodies against surface neuronal proteins (LGI1, NMDAR, CASPR2, GABABR, and AMPAR)... (Review)
Review
PURPOSE
The growing recognition of epilepsies and encephalopathies associated with autoantibodies against surface neuronal proteins (LGI1, NMDAR, CASPR2, GABABR, and AMPAR) means that epileptologists are increasingly asking questions about mechanisms of antibody-mediated epileptogenesis, and about the use of immunotherapies. This review summarizes clinical and paraclinical observations related to autoimmune epilepsies, examines the current evidence for the effectiveness of immunotherapy, and makes epilepsy-specific recommendations for future research.
METHOD
Systematic literature search with summary and review of the identified publications. Studies describing the clinical characteristics of autoantibody-associated epilepsies and treatments are detailed in tables.
RESULTS
Literature describing the clinical manifestations and treatment of autoimmune epilepsies associated with neuronal cell-surface autoantibodies (NSAbs) is largely limited to retrospective case series. We systematically summarize the features of particular interest to epileptologists dividing patients into those with acute or subacute encephalopathies associated with epilepsy, and those with chronic epilepsy without encephalopathy. Available observational studies suggest that immunotherapies are effective in some clinical circumstances but outcome data collection methods require greater standardization.
CONCLUSIONS
The clinical experience captured suggests that clusters of clinical features associate well with specific NSAbs. Intensive and early immunotherapy is indicated when patients present with autoantibody-associated encephalopathies. It remains unclear how patients with chronic epilepsy and the same autoantibodies should be assessed and treated. Tables in this paper provide a comprehensive resource for systematic descriptions of both clinical features and treatments, and highlight limitations of current studies.
Topics: Autoantibodies; Databases, Bibliographic; Epilepsy; Humans; Immunotherapy
PubMed: 27450643
DOI: 10.1016/j.seizure.2016.07.002 -
Journal of Autoimmunity Aug 2021The variability in resolution of SARS-CoV-2-infections between individuals neither is comprehended, nor are the long-term immunological consequences. To assess the...
The variability in resolution of SARS-CoV-2-infections between individuals neither is comprehended, nor are the long-term immunological consequences. To assess the long-term impact of a SARS-CoV-2-infection on the immune system, we conducted a prospective study of 80 acute and former SARS-CoV-2 infected individuals and 39 unexposed donors to evaluate autoantibody responses and immune composition. Autoantibody levels against cyclic citrullinated peptide (CCP), a specific predictor for rheumatoid arthritis (RA), were significantly (p = 0.035) elevated in convalescents only, whereas both acute COVID-19 patients and long-term convalescents showed critically increased levels of anti-tissue transglutaminase (TG), a specific predictor of celiac disease (CD) (p = 0.002). Both, anti-CCP and anti-TG antibody levels were still detectable after 4-8 months post infection. Anti-TG antibodies occurred predominantly in aged patients in a context of a post-SARS-CoV-2-specific immune composition (R = 0.31; p = 0.044). This study shows that increased anti-CCP and anti-TG autoantibody levels can remain long-term after recovering even from mildly experienced COVID-19. The inter-relationship of the lung as viral entry side and RA- and CD-associated autoimmunity indicates that a SARS-CoV-2-infection could be a relevant environmental factor in their pathogenesis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Citrullinated Protein Antibodies; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; COVID-19; Celiac Disease; Female; Humans; Male; Middle Aged; Peptides, Cyclic; Prevalence; Prospective Studies; SARS-CoV-2; Transglutaminases; Young Adult
PubMed: 34214763
DOI: 10.1016/j.jaut.2021.102682 -
Frontiers in Immunology 2019Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting cellular adhesion molecules. While IgE autoantibodies are... (Review)
Review
Bullous pemphigoid (BP) is an autoimmune blistering disease characterized by autoantibodies targeting cellular adhesion molecules. While IgE autoantibodies are occasionally reported in other autoimmune blistering diseases, BP is unique in that most BP patients develop an IgE autoantibody response. It is not known why BP patients develop self-reactive IgE and the precise role of IgE in BP pathogenesis is not fully understood. However, clinical evidence suggests an association between elevated IgE antibodies and eosinophilia in BP patients. Since eosinophils are multipotent effector cells, capable cytotoxicity and immune modulation, the putative interaction between IgE and eosinophils is a primary focus in current studies aimed at understanding the key components of disease pathogenesis. In this review, we provide an overview of BP pathogenesis, highlighting clinical and experimental evidence supporting central roles for IgE and eosinophils as independent mediators of disease and via their interaction. Additionally, therapeutics targeting IgE, the Th2 axis, or eosinophils are also discussed.
Topics: Antibodies, Monoclonal, Humanized; Autoantibodies; Cytokines; Dystonin; Eosinophilia; Eosinophils; Humans; Immunoglobulin E; Immunoglobulin G; Immunoglobulins, Intravenous; Pemphigoid, Bullous; Receptors, IgE
PubMed: 31636640
DOI: 10.3389/fimmu.2019.02331 -
Oncotarget Mar 2016Pancreatic cancer is a leading cause of cancer-related deaths in the western world. Patients with pancreatic cancer have poor prognosis, partly due to difficulties in... (Review)
Review
Pancreatic cancer is a leading cause of cancer-related deaths in the western world. Patients with pancreatic cancer have poor prognosis, partly due to difficulties in detecting it at early stages. While different markers have been associated with pancreatic cancer, many of them show suboptimal sensitivity and specificity. Serum autoantibodies against tumor-associated antigens have recently emerged as early stage biomarkers for different types of cancers. Given the urgent need for early and reliable biomarkers for pancreatic cancer, we undertook a systematic review of the published literature to identify primary articles that evaluated serum autoantibodies in pancreatic cancer detection by searching PubMed and ISI Web of Knowledge. Two reviewers extracted data on study characteristics and results independently. Overall, 31 studies evaluating 124 individual serum autoantibodies in pancreatic cancer detection met the inclusion criteria. In general, single autoantibody markers showed relatively low sensitivities at high specificity. A combination of markers, either multiple serum autoantibodies or serum autoantibodies combined with tumor-associated markers, led to a better diagnostic performance. However, most of the analyzed autoantibodies have only been reported in single studies and therefore need to be independently validated. We conclude that serum autoantibodies might present an option as biomarkers for early detection of pancreatic cancer, but more work is needed to identify and validate autoantibody signatures that are associated with early stage pancreatic cancer.
Topics: Antibodies, Neoplasm; Antigens, Neoplasm; Autoantibodies; Biomarkers, Tumor; Early Detection of Cancer; Humans; Pancreatic Neoplasms
PubMed: 26840568
DOI: 10.18632/oncotarget.7098 -
Scientific Reports Apr 2023Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as...
Patients with ACPA-positive and ACPA-negative rheumatoid arthritis show different serological autoantibody repertoires and autoantibody associations with disease activity.
Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as ACPA-positive (ACPA+) or ACPA-negative (ACPA-), respectively. In this study, we aimed to elucidate a broader range of serological autoantibodies that could further explain immunological differences between patients with ACPA+ RA and ACPA- RA. On serum collected from adult patients with ACPA+ RA (n = 32), ACPA- RA (n = 30), and matched healthy controls (n = 30), we used a highly multiplex autoantibody profiling assay to screen for over 1600 IgG autoantibodies that target full-length, correctly folded, native human proteins. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA- RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies with significantly higher abundances in ACPA+ RA patients and ACPA- RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons; this provides further evidence of immunological differences between these two RA subgroups despite sharing similar symptoms. On the other hand, we identified 30 and 25 autoantibodies with lower abundances in ACPA+ RA and ACPA- RA, respectively, of which 8 autoantibodies were common in both comparisons; we report for the first time that the depletion of certain autoantibodies may be linked to this autoimmune disease. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with Clinical Disease Activity Index, but associate differently depending on patients' ACPA status. In all, we present candidate autoantibody biomarker signatures associated with ACPA status and disease activity in RA, providing a promising avenue for patient stratification and diagnostics.
Topics: Adult; Humans; Autoantibodies; Arthritis, Rheumatoid; Anti-Citrullinated Protein Antibodies
PubMed: 37005480
DOI: 10.1038/s41598-023-32428-4 -
Brazilian Journal of Medical and... Jan 2003Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as... (Review)
Review
Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies). Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation) is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn's syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.
Topics: Animals; Antigen-Antibody Reactions; Autoantibodies; Autoantigens; Humans; Immune System; Models, Immunological; T-Lymphocytes
PubMed: 12532222
DOI: 10.1590/s0100-879x2003000100003