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Frontiers in Immunology 2022NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of...
NETosis is a form of neutrophil cell death during which extracellular fibrillary structures composed of cytosolic and granule proteins assembled on scaffolds of decondensed chromatin, called neutrophil extracellular traps (NETs), are released. NETs normally contribute to host immune defense. Accumulating evidence implicates aberrant NET production and/or reduced NET clearance, along with alterations of molecules involved in NETosis pathway, in humans and animals with lupus. The extruded nuclear antigens released by NET are a source of autoantigens, which can contribute to the breakdown of self-tolerance in lupus. Excessive NET can also promote the production of pro-inflammatory cytokine interferon-α, elicit direct cytotoxic effect on various renal cells, and cause capillary necrosis and podocyte loss. Additionally, NET can induce endothelial-to-mesenchymal transdifferentiation, which can promote activated myofibroblasts leading to extracellular matrix production. Thus, aberrant NETosis can play diverse roles, including autoantibody production, inflammation, and tissue damage, at different stages of lupus pathogenesis. Evidence suggests that treatments currently used in lupus may reduce NETosis, suggesting a potential utility of targeting NETosis to treat lupus. In fact, several approaches are being experimented to therapeutically target pathways of NETosis. Future studies should precisely delineate distinct roles of NETosis at different stages of lupus pathogenesis in humans, which would offer a rational basis for NETosis-targeting treatments in the clinic.
Topics: Animals; Autoantigens; Cell Death; Extracellular Traps; Inflammation; Neutrophils
PubMed: 35686129
DOI: 10.3389/fimmu.2022.895216 -
BMC Pregnancy and Childbirth Jul 2020Thyroid dysfunction during pregnancy is associated with adverse outcomes for both mother and fetus. The present meta-analysis was conducted to evaluate thyroid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thyroid dysfunction during pregnancy is associated with adverse outcomes for both mother and fetus. The present meta-analysis was conducted to evaluate thyroid dysfunction in Iranian pregnant women.
METHODS
We registered this review at PROSPERO (registration number: CRD42020166655). The research steps in this systematic review and meta-analysis were performed according to the MOOSE protocol, and finally, reports were provided based on the PRISMA guidelines. The literature search was performed in October 2019 using the international online databases, including Web of Science, Ovid, Science Direct, Scopus, EMBASE, PubMed/Medline, Cochrane Library, EBSCO, CINAHL, Google Scholar as well as national databases were reviewed. Data were extracted after applying the inclusion and exclusion criteria and qualitative evaluation of the studies. I index and Q test were used to assess differences in studies. All analyses were performed using Comprehensive Meta-Analysis Software. P-value less than 0.05 was considered statistically significant. We identified 1261 potential articles from the databases, and 426 articles remained after removing the duplicate and unrelated studies. After evaluating the full text, 52 articles were removed.
RESULTS
Finally, 19 eligible studies including 17,670 pregnant women included for meta-analysis. The prevalence of thyroid dysfunction in Iranian pregnant women was 18.10% (95%CI: 13.89-23.25). The prevalence of hypothyroidism, clinical hypothyroidism, and subclinical hypothyroidism in Iranian pregnant women was respectively estimated to be 13.01% (95%CI: 9.15-18.17), 1.35% (95%CI: 0.97-1.86) and 11.90% (95%CI: 7.40-18.57). The prevalence of hyperthyroidism, clinical hyperthyroidism, and subclinical hyperthyroidism in Iranian pregnant women was respectively estimated to be 3.31% (95%CI: 1.62-6.61), 1.06% (95%CI: 0.61-1.84) and 2.56% (95%CI: 0.90-7.05). The prevalence of anti-thyroperoxidase antibody was estimated to be 11.68% (95%CI: 7.92-16.89).
CONCLUSION
The results of this meta-analysis showed a high prevalence of thyroid disorders, especially hypothyroidism. The decision to recommend thyroid screening during pregnancy for all women is still under debate, because the positive effects of treatment on pregnancy outcomes must be ensured. On the other hand, evidence about the effect of thyroid screening and treatment of thyroid disorders on pregnancy outcomes is still insufficient. Nevertheless, a large percentage of general practitioners, obstetricians and gynecologists perform screening procedures in Iran.
Topics: Adult; Autoantigens; Female; Humans; Hypothyroidism; Iodide Peroxidase; Iran; Iron-Binding Proteins; Pregnancy; Pregnancy Complications; Thyroid Diseases
PubMed: 32664874
DOI: 10.1186/s12884-020-03040-5 -
Multiple Sclerosis and Related Disorders Sep 2021the distinct MRI features of MOG-antibody disease (MOG-AD) and AQP4-NMOSD are still poorly defined. We performed a systematic review and meta-analysis to identify... (Meta-Analysis)
Meta-Analysis
BACKGROUND
the distinct MRI features of MOG-antibody disease (MOG-AD) and AQP4-NMOSD are still poorly defined. We performed a systematic review and meta-analysis to identify specific patterns of MRI abnormalities able to discriminate between MOG-AD and AQP4-NMOSD.
METHODS
fourteen case-series (1028 patients) were included. Outcomes were MRI lesion patterns in optic nerve (ON), brain and spinal cord (SC) that were selected after a systematic literature review and analysed separately as the event rate for individual MRI lesions in MOG-AD (experimental group) and AQP4-NMOSD (control group) by using a random effect model.
RESULTS
MOG-AD showed a higher number of MRI lesions than AQP4-NMOSD patients in the retrobulbar ON (OR=5.67; 95%CI=2.11-15.24; p=0.0006) with ON head swelling (OR=8.20; 95%CI=4.13-16.28; p<0.00001), corpus callosum (OR=2.30; 95%CI=1.11-4.76; p=0.02), pons (OR=2.87; 95%CI=1.45-5.67; p=0.002), and lumbar/conus SC (OR=3.47; 95%CI=1.66-7.24; p=0.0009). Conversely, lesions in the canalicular (OR=0.42; 95%CI=0.18-0.98; p=0.05) and intracranial ON (OR=0.30; 95%CI=0.11=0.84; p=0.02), area postrema (OR=0.12; 95%CI=0.02-0.61; p=0.01), medulla (OR=0.40; 95%CI=0.20-0.78; p=0.007), and cervical SC (OR=0.29; 95%CI=0.09-0.92; p=0.04) were prominent in patients with AQP4-NMOSD. Participants' age was found to be a source of heterogeneity across studies.
CONCLUSION
our study provides further evidence that MOG-AD and AQP4-NMOSD have distinct MRI features that may help clinicians for an early differential diagnosis.
Topics: Aquaporin 4; Autoantibodies; Humans; Magnetic Resonance Imaging; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica
PubMed: 34246019
DOI: 10.1016/j.msard.2021.103118 -
Journal of the European Academy of... Jan 2016Mucous membrane pemphigoid (MMP) is characterized by subepithelial blistering due to IgG autoantibodies targeting various components of the dermal-epidermal basement... (Review)
Review
A systematic review with pooled analysis of clinical presentation and immunodiagnostic testing in mucous membrane pemphigoid: association of anti-laminin-332 IgG with oropharyngeal involvement and the usefulness of ELISA.
BACKGROUND
Mucous membrane pemphigoid (MMP) is characterized by subepithelial blistering due to IgG autoantibodies targeting various components of the dermal-epidermal basement membrane zone. Immunodiagnostics play an important role in making a precise diagnosis. Measures of test sensitivity and specificity, however, typically come from studies in diseases such as bullous pemphigoid, where the exact antigenic site may not be the same. Additionally, the association of clinical phenotype and autoantibody profiles has been an area of debate.
OBJECTIVE
We evaluated the sensitivity and specificity of ELISA in MMP for the known target antigens BP180 and laminin-332, as well as characterized the frequency of IgG antibodies against each laminin-332 subdomain. Lastly, we analysed whether IgG auto-antibody profiles were associated with clinical phenotype.
METHODS
We performed a systematic review of Medline/PubMed to compile MMP patient demographics, clinical manifestations and immunodiagnostic results. ELISA sensitivities and specificities for autoantigens were calculated in patients with positive immunoblot or immunoprecipitationstudies. IgG reactivity for each laminin-332 subunit was recorded. Associations between positive immunological tests and clinical presentation were evaluated using chi-squared test tests or Fisher's exact test when appropriate.
RESULTS
For patients with a positive immunoblot or immunoprecipitation to NC16a, ELISA using both the NC16a and C-terminal portion of BP180 demonstrated a sensitivity and specificity of 73% and 93%. However, for individuals with IgG against the C-terminal domain of BP180, the sensitivity and specificity was 43% and 56%, respectively. LN-332 ELISA demonstrated 75% sensitivity, but only for patients with IgG reactivity against the α3 subunit. In patients with laminin-332 MMP, 86.4% demonstrated IgG against the α3 subunit. IgG autoantibodies against laminin-332 are significantly associated with pharyngo-laryngeal (P < 0.0001) and oro-pharyngo-laryngeal (P = 0.006) involvement.
CONCLUSIONS
Immunodiagnostics play a major role in diagnosing MMP, though limited sensitivity may necessitate several forms of testing for confirmation.
Topics: Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Laminin; Oropharynx; Pemphigoid, Benign Mucous Membrane; Phenotype; Sensitivity and Specificity
PubMed: 26446477
DOI: 10.1111/jdv.13397 -
Archives of Dermatological Research Jan 2018Bullous pemphigoid (BP) is the most common autoimmune skin disease of blistering character. The underlying pathophysiological mechanism involves an immune attack,... (Review)
Review
Bullous pemphigoid (BP) is the most common autoimmune skin disease of blistering character. The underlying pathophysiological mechanism involves an immune attack, usually by IgG class autoantibodies, on the autoantigen BP 180/BPAg2, which is a type XVII collagen (COL17) protein acting as the adhesion molecule between the epidermis and the basement membrane of the dermis. About 40 years ago, following consistent findings of elevated total serum IgE levels in BP patients, it was hypothesized that IgE may be involved in the pathophysiology of BP. Our objective was to determine whether there is strong evidence for an association between IgE class autoantibodies and the clinical severity or phenotype of BP. Three databases were searched for relevant studies and appropriate exclusion and inclusion criteria were applied. Data was extracted and assessed in relation to the study questions concerning the clinical significance of IgE autoantibodies in BP. Nine studies found that anti-BP180 autoantibodies of IgE class are associated with increased severity of BP, whereas two studies did not find such an association. The number of studies which found an association between higher IgE autoantibody levels and the erythematous urticarial phenotype of BP (5) was equal in number to the studies which found no such association (5). In conclusion, higher serum IgE autoantibody levels are associated with more severe clinical manifestations of BP. There is insufficient evidence to support higher IgE autoantibody levels being associated with specific clinical phenotypes of BP.
Topics: Autoantibodies; Humans; Immunoglobulin E; Pemphigoid, Bullous; Phenotype; Severity of Illness Index
PubMed: 29071428
DOI: 10.1007/s00403-017-1789-1 -
Cureus May 2024Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study... (Review)
Review
Autoimmune hepatitis (AIH) is a hepatocellular disorder thought to be caused by an immune system that cannot tolerate autoantigens specific to hepatocytes. This study aims to evaluate the efficacy of using corticosteroids (prednisolone and azathioprine) as a combination therapy in treating AIH. This study aims to synthesize and analyze existing evidence to inform clinical practices concerning the overall clinical efficacy of this treatment approach in managing AIH. A comprehensive search was conducted across multiple online databases and search engines, including PubMed, Google Scholar, ScienceDirect, Medline, and Embase. RevMan 5.4 software was used for meta-analysis, with forest plots created for each outcome. Thirteen studies were included in this systematic review and meta-analysis. The results indicate that the combination of prednisolone and azathioprine for treating AIH leads to less recurrence and better disease control.
PubMed: 38854256
DOI: 10.7759/cureus.60049 -
Frontiers in Immunology 2023Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease...
BACKGROUND AND PURPOSE
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has gained recognition in recent years as an immune-mediated inflammatory demyelinating disease of the central nervous system. The clinical features and prognosis of MOGAD adult cerebral cortical encephalitis (adult CCE) have not been fully elucidated. This study aims to further characterize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of CCE with anti-MOG antibody.
METHODS
We present two adult cases of CCE with anti-MOG antibody and summarize the clinical symptoms, magnetic resonance imaging (MRI) findings, and prognosis of this phenotype as per a completed systematic review of the literature.
RESULTS
We found a total of 39 cases of MOGAD adult CCE (36% females; average age of onset of 29 years). Among them, 85% had seizure, 82% had headache, 64% had cortical symptoms, 64% had fever, 54% had changes of consciousness, and 38% had ocular symptoms. All cases demonstrated cerebral cortical T2 fluid-attenuated inversion recovery (FLAIR) lesions on MRI. Of the 25 patients (with seizure or not) who had EEG reports, 76% of patients showed abnormal EEG. Cerebrospinal fluid (CSF) white blood cell count of 90% of patients and CSF total protein of 67% of patients were elevated. In 16 patients with available CSF cytology data, 11 (69%) had abnormal cytology findings with monocytic predominance. In the 15 cases for which MOG antibody IgG was tested in both serum and CSF, 14 (93%) demonstrated a higher positive MOG IgG titer in serum than CSF. The majority of patients were treated with immunosuppressive therapy (97% corticosteroids, 15% mycophenolate mofetil, 13% IVIg, 5% azathioprine, and 5% other). The majority of patients had a favorable prognosis after treatment, as exemplified by improved clinical symptoms and imaging. Two patients relapsed.
CONCLUSIONS
The clinical presentation and prognosis of adult CCE remain less understood in comparison to more common MOGAD phenotypes. It is important to consider MOGAD as an underlying etiology for adult CCE, as early detection and immunotherapy may improve outcomes.
Topics: Female; Male; Humans; Myelin-Oligodendrocyte Glycoprotein; Autoantibodies; Encephalitis; Seizures; Immunoglobulin G; Oligodendroglia
PubMed: 37520572
DOI: 10.3389/fimmu.2023.1203615 -
Sixteen-year history of rituximab therapy for 1085 pemphigus vulgaris patients: A systematic review.International Immunopharmacology Jan 2018Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin... (Review)
Review
Pemphigus vulgaris (PV) is a rare autoimmune disease due to the production of pathogenic autoantibodies directed against desmoglein 1 and 3, usually affecting both skin and mucous membranes. Recently, rituximab, a chimeric IgG1 monoclonal antibody which targets the CD20 molecules have been regarded as a promising treatment for PV. In this study, a systematic review was conducted to conclude on how and which PV patients could benefit from rituximab infusion. Search in PubMed results in 114 relevant studies, which met the criteria. Total of 1085 PV patients with different conditions, including unresponsive childhood/juvenile or adult PV patients, women of childbearing age, those with chronic infections with the risk of reactivation have been evaluated. Although the majority of these patients well responded to rituximab, some of them did not respond, and the paucity of patients experienced exacerbation of disease. In addition to the rituximab monotherapy or its combination with conventional therapies, different novel combination therapies of rituximab with immunoadsorption and/or IVIg have shown promising results. Moreover, using rituximab as the first-line treatment has emerged recently. Pneumocystis carinii pneumonia and septicemia were found as the two fatal and serious adverse events associated with rituximab. Moreover, development or reactivation of herpes simplex and herpes zoster and cytomegalovirus should be warned. Similar to the adults, those with childhood and juvenile PV could be successfully treated with rituximab. Although rituximab seems to trigger reactivation of chronic infections, such as viral hepatitis and HIV infection, no related report was found. Administration of rituximab in approximately ten months before conception also was found safe and effective for a successful pregnancy. In conclusion, rituximab is very effective in adult and childhood/juvenile PV. However, there is a risk of not responding, exacerbation of disease and development of fatal infections. Moreover, it seems to be a promising first-line treatment for refractory PV.
Topics: Antigens, CD20; Autoantibodies; Combined Modality Therapy; Desmoglein 1; Desmoglein 3; Drug-Related Side Effects and Adverse Reactions; Herpesviridae; Humans; Immunoglobulins, Intravenous; Immunotherapy; Mucous Membrane; Pemphigus; Rituximab; Skin; Virus Activation
PubMed: 29132070
DOI: 10.1016/j.intimp.2017.11.005 -
Journal of Neuroimmunology Dec 2018This meta-analysis aimed to systematically review current literature measuring the thickness of retinal nerve fiber layer (RNFL) in patients with myelin oligodendrocyte... (Meta-Analysis)
Meta-Analysis Review
This meta-analysis aimed to systematically review current literature measuring the thickness of retinal nerve fiber layer (RNFL) in patients with myelin oligodendrocyte glycoprotein antibodies (MOG-ab) associated optic neuritis. Ten studies were enrolled and the results showed that the degree of RNFL loss in MOG-ab-positive optic neuritis patients may not differ from that of AQP4-ab patients. However, patients who were positive for MOG-ab showed more severe RNFL loss than those who were seronegative.
Topics: Animals; Autoantibodies; Humans; Myelin-Oligodendrocyte Glycoprotein; Nerve Fibers; Observational Studies as Topic; Optic Neuritis; Retina; Retinal Neurons
PubMed: 30290966
DOI: 10.1016/j.jneuroim.2018.09.011 -
Frontiers in Immunology 2022The antiphospholipid syndrome (APS) is a thrombotic autoimmune disease in which the origin of the disease-characterizing autoantibodies is unknown. Increased research...
The antiphospholipid syndrome (APS) is a thrombotic autoimmune disease in which the origin of the disease-characterizing autoantibodies is unknown. Increased research effort into the role of the intestinal microbiome in autoimmunity has produced new insights in this field. This scoping review focusses on the gut microbiome in its relation to APS. EMBASE and MEDLINE were searched for original studies with relevance to the relation between the gut microbiome and APS. Thirty studies were included. Work on systemic lupus erythematosus, which strongly overlaps with APS, has shown that patients often display an altered gut microbiome composition, that the disease is transferable with the microbiome, and that microbiome manipulation affects disease activity in murine lupus models. The latter has also been shown for APS, although data on microbiome composition is less consistent. APS patients do display an altered intestinal IgA response. Evidence has accrued for molecular mimicry as an explanatory mechanism for these observations in APS and other autoimmune diseases. Specific gut microbes express proteins with homology to immunodominant APS autoantigens. The disease phenotype appears to be dependent on these mimicking proteins in an APS mouse model, and human APS B- and T-cells indeed cross-react with these mimics. Pre-clinical evidence furthermore suggests that diet may influence autoimmunity through the microbiome, as may microbial short chain fatty acid production, though this has not been studied in APS. Lastly, the microbiome has been shown to affect key drivers of thrombosis, and may thus affect APS severity through non-immunological mechanisms. Overall, these observations demonstrate the impact of the intestinal microbiome on autoimmunity and the importance of understanding its role in APS.
Topics: Humans; Mice; Animals; Antiphospholipid Syndrome; Gastrointestinal Microbiome; Microbiota; Autoimmune Diseases; Autoimmunity
PubMed: 36505427
DOI: 10.3389/fimmu.2022.954764