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Frontiers in Molecular Biosciences 2023Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the... (Review)
Review
Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.
PubMed: 37614441
DOI: 10.3389/fmolb.2023.1215039 -
Neurosurgical Review Sep 2023Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been...
Despite more than six decades of extensive research, the etiology of moyamoya disease (MMD) remains unknown. Inflammatory or autoimmune (AI) processes have been suggested to instigate or exacerbate the condition, but the data remains mixed. The objective of the present systematic review was to summarize the available literature investigating the association of MMD and AI conditions as a means of highlighting potential treatment strategies for this subset of moyamoya patients. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the PubMed, Embase, Scopus, Web of Science, and Cochrane databases were queried to identify studies describing patients with concurrent diagnoses of MMD and AI disease. Data were extracted on patient demographics, clinical outcomes, and treatment. Stable or improved symptoms were considered favorable outcomes, while worsening symptoms and death were considered unfavorable. Quantitative pooled analysis was performed with individual patient-level data. Of 739 unique studies identified, 103 comprising 205 unique patients (80.2% female) were included in the pooled analysis. Most patients (75.8%) identified as Asian/Pacific Islanders, and the most commonly reported AI condition was Graves' disease (57.6%), with 55.9% of these patients presenting in a thyrotoxic state. Of the 148 patients who presented with stroke, 88.5% of cases (n = 131) were ischemic. Outcomes data was available in 152 cases. There were no significant baseline differences between patients treated with supportive therapy alone and those receiving targeted immunosuppressant therapy. Univariable logistic regression showed that surgery plus medical therapy was more likely than medical therapy alone to result in a favorable outcome. On subanalysis of operated patients, 94.1% of patients who underwent combined direct and indirect bypass reported favorable outcomes, relative to 76.2% of patients who underwent indirect bypass and 82% who underwent direct bypass (p < 0.05). On univariable analysis, the presence of multiple AI disorders was associated with worse outcomes relative to having a single AI disorder. Autoimmune diseases have been uncommonly reported in patients with MMD, but the presence of multiple AI comorbidities portends poorer prognosis. The addition of surgical intervention appears to improve outcomes and for patients deemed surgical candidates, combined direct and indirect bypass appears to offer better outcomes that direct or indirect bypass alone.
Topics: Humans; Female; Male; Moyamoya Disease; Autoimmune Diseases; Stroke; Databases, Factual
PubMed: 37658996
DOI: 10.1007/s10143-023-02123-z -
Allergy, Asthma, and Clinical... Aug 2023Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal... (Review)
Review
OBJECTIVES
Immunoglobulin A deficiency (IgAD) is a common disease with an unknown genetic defect, characterized by the decreased or absent IgA with other isotypes normal, normal subclasses, and specific antibodies. Patients with this disorder represent a spectrum of clinical manifestations including infections, autoimmune disorders, malignancy, and allergic diseases. The current study aimed to evaluate their prevalence and categorized them.
METHODS
We searched PubMed, Web of Science, and Scopus databases to find eligible studies from the earliest available date to January 2022 with standard keywords. Pooled estimates of clinical manifestations prevalence and the corresponding 95% confidence intervals were calculated using random-effects models.
RESULTS
The most prevalent clinical manifestations belonged to infection (64.8%) followed by allergic diseases (26.16%) and autoimmunity (22.0%), respectively. In selective IgA deficiency patients as the largest group of IgAD in current study, celiac disease (6.57%), Inflammatory bowel disease (4.01%), and rheumatoid arthritis (3.80%) were the most prevalent autoimmunity. Meanwhile, the most frequent infection was respiratory tract infection, fungal infection, and gastrointestinal infection at 50.74%, 18.48%, and 15.79%, respectively. In addition, the pooled prevalence of asthma, allergic rhinitis, and allergic conjunctivitis were 19.06%, 15.46%, and 11.68%, respectively which were reported as the most widespread allergic diseases.
CONCLUSIONS
Our results showed that apart from undiagnosed IgAD patients, IgAD patients represent a wide range of clinical manifestations. Infection, allergy, and autoimmunity are the most common clinical manifestations. The concurrent presence of IgA and IgG subtypes deficiency could be associated with increased susceptibility to infection. Considering the probability of developing new clinical complications during follow-up, periodic assessments of IgAD patients should be inspected.
PubMed: 37641141
DOI: 10.1186/s13223-023-00826-y -
Frontiers in Immunology 2023Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability...
Rheumatoid arthritis (RA) is an autoimmune disease that currently has an unknown cause and pathogenesis, and is associated with many complications and a high disability rate. The neutrophil extracellular trap network (NETs) is a newly discovered mechanism that allows neutrophils to capture and kill pathogens. Multiple studies in recent years have highlighted its relevance to the progression of rheumatoid arthritis. Despite the growing number of studies indicating the crucial role of NETs in RA, there has been no bibliometric review of research hotspots and trends in this area. In this study, we retrieved articles related to NETs in RA from the Web of Science Core Collection (WoSCC) database from 1985 to 2023 and used visualization tools such as Citespace, VOSviewer, Tableau Public, and Microsoft Office Excel 2021 to analyze the data. After screening, we included a total of 416 publications involving 2,334 researchers from 1,357 institutions in 167 countries/regions, with relevant articles published in 219 journals. The U.S., China, and Germany are the top 3 countries/regions with 124, 57, and 37 publications respectively. Mariana J. Kaplan is the most published author, and journals such as Frontiers in Immunology and International Journal of Molecular Sciences have had a significant impact on research in this field. The clinical application of PAD enzymes and their inhibitors, and the drug development of NETs as therapeutic targets for RA is a trend for future research. Our study provides a comprehensive bibliometric analysis and summary of NETs in RA publications, which will aid researchers in conducting further scientific research.
Topics: Humans; Extracellular Traps; Arthritis, Rheumatoid; Autoimmune Diseases; Neutrophils; Bibliometrics
PubMed: 37680637
DOI: 10.3389/fimmu.2023.1205445 -
Acta Neurologica Belgica Dec 2023We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We aimed to synthesize all available observational studies and clinical trials of rituximab to estimate the safety and efficacy of this monoclonal antibody in people with multiple sclerosis (MS).
METHODS
The four databases including PubMed, Scopus, Embase, and Web of Science were comprehensively searched in April 2022. We defined PICO as follows. Problem or study population (P): patients with MS; intervention (I): Rituximab; comparison (C): none; outcome (O): efficacy and safety.
RESULTS
After two-step screening, a total of 27 studies entered into our qualitative and quantitative synthesis. Our analysis showed a significant decrease in EDSS score in all patients with MS after treatment (SMD: - 0.44, 95% CI - 0.85, - 0.03). In addition, the ARR was reduced after using rituximab compared to the pre-treatment period (SMD: - 0.65, 95% CI - 1.55, 0.24) but it was not significant. The most common side effect after rituximab with a pooled prevalence of 28.63% (95% CI 16.61%, 42.33%). Furthermore, the pooled prevalence of infection was 24% in patients with MS (95% CI 13%, 36%). In the end, the pooled prevalence of malignancies after rituximab treatment was 0.39% (95% CI 0.02%, 1.03%).
CONCLUSION
Our findings illustrated an acceptable safety for this treatment. However, further studies with randomized design, long follow-up, and large sample sizes are needed to confirm the safety and efficacy of rituximab in patients with MS.
Topics: Humans; Rituximab; Multiple Sclerosis; Antibodies, Monoclonal
PubMed: 37428437
DOI: 10.1007/s13760-023-02329-4 -
Journal of Neurology Nov 2023To systematically review the published cases of bilateral facial palsy (BFP) to gather evidence on the clinical assessment and management of this pathology. (Review)
Review
OBJECTIVE
To systematically review the published cases of bilateral facial palsy (BFP) to gather evidence on the clinical assessment and management of this pathology.
METHODS
Following PRISMA statement recommendations, 338 abstracts were screened independently by two authors. Inclusion criteria were research articles of human patients affected by BFP, either central or peripheral; English, Italian, French or Spanish language; availability of the abstract, while exclusion criteria were topics unrelated to FP, and mention of unilateral or congenital FP. Only full-text articles reporting the diagnostic work-up, the management, and the prognosis of the BFP considered for further specific data analysis.
RESULTS
A total of 143 articles were included, resulting a total of 326 patients with a mean age of 36 years. The most common type of the paralysis was peripheral (91.7%), and the autoimmune disease was the most frequent aetiology (31.3%). The mean time of onset after first symptoms was 12 days and most patients presented with a grade higher than III. Associated symptoms in idiopathic BFP were mostly non-specific. The most frequently positive laboratory exams were cerebrospinal fluid analysis, autoimmune screening and peripheral blood smear, and the most performed imaging was MRI. Most patients (74%) underwent exclusive medical treatment, while a minority were selected for a surgical or combined approach. Finally, in more than half of cases a complete bilateral recovery (60.3%) was achieved.
CONCLUSIONS
BFP is a disabling condition. If a correct diagnosis is formulated, possibilities to recover are elevated and directly correlated to the administration of an adequate treatment.
Topics: Humans; Adult; Facial Paralysis; Facial Nerve Diseases; Causality; Magnetic Resonance Imaging
PubMed: 37523065
DOI: 10.1007/s00415-023-11897-7 -
Vaccines Sep 2023Patients with autoimmune diseases are among the susceptible groups to COVID-19 infection because of the complexity of their conditions and the side effects of the... (Review)
Review
Patients with autoimmune diseases are among the susceptible groups to COVID-19 infection because of the complexity of their conditions and the side effects of the immunosuppressive drugs used to treat them. They might show impaired immunogenicity to COVID-19 vaccines and have a higher risk of developing COVID-19. Using a systematic review and meta-analysis, this research sought to summarize the evidence on COVID-19 vaccine efficacy, immunogenicity, and safety in patients with autoimmune diseases following predefined eligibility criteria. Research articles were obtained from an initial search up to 26 September 2022 from PubMed, Embase, EBSCOhost, ProQuest, MedRxiv, bioRxiv, SSRN, EuroPMC, and the Cochrane Center of Randomized Controlled Trials (CCRCT). Of 76 eligible studies obtained, 29, 54, and 38 studies were included in systematic reviews of efficacy, immunogenicity, and safety, respectively, and 6, 18, and 4 studies were included in meta-analyses for efficacy, immunogenicity, and safety, respectively. From the meta-analyses, patients with autoimmune diseases showed more frequent breakthrough COVID-19 infections and lower total antibody (TAb) titers, IgG seroconversion, and neutralizing antibodies after inactivated COVID-19 vaccination compared with healthy controls. They also had more local and systemic adverse events after the first dose of inactivated vaccination compared with healthy controls. After COVID-19 mRNA vaccination, patients with autoimmune diseases had lower TAb titers and IgG seroconversion compared with healthy controls.
PubMed: 37766132
DOI: 10.3390/vaccines11091456 -
European Radiology Dec 2023To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic accuracy.
METHODS
A systematic and detailed literature review was performed through PubMed, EMBASE, and the Cochrane library. Similar descriptors to embody the identical image finding were labeled as a single CT characteristic. We calculated the pooled diagnostic odds ratios (DORs) of each CT characteristic using a bivariate random-effects model.
RESULTS
A total of 145 various descriptors from 15 studies (including 562 AIP and 869 PDAC patients) were categorized into 16 CT characteristics. According to the pooled DOR, 16 CT characteristics were classified into three groups (suggesting AIP, suggesting PDAC, and not informational). Seven characteristics suggesting AIP were diffuse pancreatic enlargement (DOR, 48), delayed homogeneous enhancement (DOR, 46), capsule-like rim (DOR, 34), multiple pancreatic masses (DOR, 16), renal involvement (DOR, 15), retroperitoneal fibrosis (DOR, 13), and bile duct involvement (DOR, 8). Delayed homogeneous enhancement showed a pooled sensitivity of 83% and specificity of 85%. The other six characteristics showed relatively low sensitivity (12-63%) but high specificity (93-99%). Four characteristics suggesting PDAC were discrete pancreatic mass (DOR, 23), pancreatic duct cutoff (DOR, 16), upstream main pancreatic duct dilatation (DOR, 8), and upstream parenchymal atrophy (DOR, 7).
CONCLUSION
Eleven CT characteristics were informational to distinguish AIP from PDAC. Diffuse pancreatic enlargement, delayed homogeneous enhancement, and capsule-like rim suggested AIP with the highest DORs, whereas discrete pancreatic mass suggested PDAC. However, pooled sensitivities of informational CT characteristics were moderate.
CLINICAL RELEVANCE STATEMENT
This meta-analysis underscores eleven distinctive CT characteristics that aid in differentiating autoimmune pancreatitis from pancreatic adenocarcinoma, potentially preventing misdiagnoses in patients presenting with focal/diffuse pancreatic enlargement.
KEY POINTS
• Diffuse pancreatic enlargement (pooled diagnostic odds ratio [DOR], 48), delayed homogeneous enhancement (46), and capsule-like rim (34) were CT characteristics suggesting autoimmune pancreatitis. • The CT characteristics suggesting autoimmune pancreatitis, except delayed homogeneous enhancement, had a general tendency to show relatively low sensitivity (12-63%) but high specificity (93-99%). • Discrete pancreatic mass (pooled diagnostic odds ratio, 23) was the CT characteristic suggesting pancreatic ductal adenocarcinoma with the highest pooled DORs.
Topics: Humans; Pancreatic Neoplasms; Autoimmune Pancreatitis; Pancreatitis; Adenocarcinoma; Tomography, X-Ray Computed; Autoimmune Diseases; Carcinoma, Pancreatic Ductal; Diagnosis, Differential
PubMed: 37466708
DOI: 10.1007/s00330-023-09959-5 -
European Journal of Neurology Jul 2024This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was undertaken to provide a comprehensive review of neuroimaging characteristics and corresponding clinical phenotypes of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A), a rare but severe neuroinflammatory disorder, to facilitate early diagnosis and appropriate treatment.
METHODS
A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis)-conforming systematic review and meta-analysis was performed on all available data from January 2016 to June 2023. Clinical and neuroimaging phenotypes were extracted for both adult and paediatric forms.
RESULTS
A total of 93 studies with 681 cases (55% males; median age = 46, range = 1-103 years) were included. Of these, 13 studies with a total of 535 cases were eligible for the meta-analysis. Clinically, GFAP-A was often preceded by a viral prodromal state (45% of cases) and manifested as meningitis, encephalitis, and/or myelitis. The most common symptoms were headache, fever, and movement disturbances. Coexisting autoantibodies (45%) and neoplasms (18%) were relatively frequent. Corticosteroid treatment resulted in partial/complete remission in a majority of cases (83%). Neuroimaging often revealed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities (74%) as well as perivascular (45%) and/or leptomeningeal (30%) enhancement. Spinal cord abnormalities were also frequent (49%), most commonly manifesting as longitudinally extensive myelitis. There were 88 paediatric cases; they had less prominent neuroimaging findings with lower frequencies of both T2/FLAIR hyperintensities (38%) and contrast enhancement (19%).
CONCLUSIONS
This systematic review and meta-analysis provide high-level evidence for clinical and imaging phenotypes of GFAP-A, which will benefit the identification and clinical workup of suspected cases. Differential diagnostic cues to distinguish GFAP-A from common clinical and imaging mimics are provided as well as suitable magnetic resonance imaging protocol recommendations.
Topics: Humans; Astrocytes; Autoantibodies; Autoimmune Diseases of the Nervous System; Glial Fibrillary Acidic Protein; Neuroimaging; Neuroinflammatory Diseases; Phenotype
PubMed: 38506182
DOI: 10.1111/ene.16284 -
Epilepsia Open Dec 2023Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the... (Review)
Review
Several reports have described the autoimmune encephalitis' (AE) possible onset during pregnancy. In this systematic review, we summarize the available data on the diagnostic and therapeutic approach to AE during pregnancy, highlighting the associated maternal and fetal clinical outcomes. A systematic search of the literature was performed. The following databases were used: PubMed, Google Scholar, EMBASE, and CrossRef. The revision was registered on the PROSPERO platform (CRD42022336357). Forty-nine patients were included. AE onset was mainly observed during the first and the second trimester of pregnancy with psychiatric manifestations and seizures as main onset symptoms. CSF analysis showed AE-specific autoantibody positivity in 33 patients (anti-NMDA receptor as the most frequent). EEG generally showed normal findings. MRI revealed pathological findings in less than half of patients. Tumor screening was positive in 14 cases. First-line immunotherapy (single or combined) was generally employed while second line was administered in a minority of patients. Levetiracetam was the most used antiseizure medication. Cesarean section was performed in 18 women. Most of the women had an excellent early outcome after delivery but 22 showed persistent neurological deficits in long-term follow-up. Fetal outcome was positive in 33 cases, whereas 12 cases of fetal death were reported. A logistic regression showed that no variable significantly influenced the odds of good/bad maternal and fetal clinical outcome. Diagnosis and treatment of AE during pregnancy is challenging. The rate of miscarriage in women with AE seems to be higher than the general population. In addition, mothers may show long-term neurological deficits.
Topics: Humans; Pregnancy; Female; Cesarean Section; Encephalitis; Abortion, Spontaneous; Autoimmune Diseases of the Nervous System
PubMed: 37562964
DOI: 10.1002/epi4.12806