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Journal of Neurology Feb 2023Retina thickness has been studied in patients with neuromyelitis optica spectrum disorders (NMOSD) without distinguishing serostatus and limited data are available in... (Meta-Analysis)
Meta-Analysis Review
Retina thickness in clinically affected and unaffected eyes in patients with aquaporin-4 immunoglobulin G antibody seropositive neuromyelitis optica spectrum disorders: a systematic review and meta-analysis.
BACKGROUND AND PURPOSE
Retina thickness has been studied in patients with neuromyelitis optica spectrum disorders (NMOSD) without distinguishing serostatus and limited data are available in unaffected eyes. We aimed to investigate retina thickness in eyes of aquaporin-4 immunoglobulin G antibody seropositive (AQP4-IgG) NMOSD patients with optic neuritis (AQP4-ON) and without (AQP4-NON).
METHODS
Eligible studies were identified by searching PubMed and Embase. Mean difference (MD, μm) with corresponding 95% confidence interval (CI) was pooled with random-effect models. The primary measures were average thickness of peripapillar retinal nerve fiber layer (pRNFL) centered on optic disc and the combination of ganglion cell layer and inner plexiform layer (GCIPL) at macula.
RESULTS
We included 21 studies enrolling 787 AQP4-IgG NMOSD patients. Compared with healthy control, pRNFL was thinner in eyes of AQP4-ON (- 32.78, 95% CI [- 36.24, - 29.33]) and AQP4-NON (- 2.76, 95% CI [- 3.94, - 1.58]), so was GICPL in AQP4-ON (-21.38, 95% CI [- 24.01, - 18.74]) and AQP4-NON (95% CI - 2.96, [- 3.91, - 2.00]). Compared with multiple sclerosis with ON, AQP4-ON had thinner pRNFL (- 13.56, 95%CI [- 16.51, - 10.60]) and GCIPL (- 9.12, 95% CI [- 11.88, - 6.36]). AQP4-ON and myelin oligodendrocyte glycoprotein antibody-associated demyelination with ON (MOG-ON) had similar pRNFL (0.59, 95% CI [- 6.61, 7.79]) and GCIPL thickness (- 0.55, 95% CI [- 2.92, 1.82]). AQP4-NON had similar pRNFL and GCIPL thickness to MOG-NON and multiple sclerosis without ON.
CONCLUSIONS
The average thickness of pRNFL and GICPL decreased both in AQP4-ON and AQP4-NON eyes. AQP4-ON eyes had a similar level of pRNFL and GICPL thinning to MOG-ON eyes, so did AQP4-NON to MOG-NON eyes.
Topics: Humans; Neuromyelitis Optica; Immunoglobulin G; Aquaporin 4; Tomography, Optical Coherence; Retina; Optic Neuritis; Multiple Sclerosis; Autoantibodies; Myelin-Oligodendrocyte Glycoprotein
PubMed: 36355186
DOI: 10.1007/s00415-022-11482-4 -
Fundamental & Clinical Pharmacology Apr 2023Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of... (Meta-Analysis)
Meta-Analysis Review
Cell therapy procedure using anti-inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta-analysis study.
Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta-analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on Clinical Score and motor impairment in EAE-induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using "Experimental Autoimmune Encephalomyelitis," "Multiple Sclerosis," and "Macrophage M2" keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of Clinical Score (score 0-5) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and I index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. P < 0.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta-analysis. Difference in means, P value, and I for Onset, Peak, and Recovery phases were 0.082 (CI95%: -0.323-0.159, P value: 0.504, I : 67.961%), -0.606 (CI95%: -1.518 to -0.305, P value: 0.192, I : 96.070%), and -1.103 (CI95%: -1.390 to -0.816, P value: 0.000, I : 30.880%), respectively and Overall Effect was found -0.509 (CI95%: -0.689 to -0.328, P value < 0.001). Also, P value (two-tailed) indices for publication bias were 0.366 and 0.583 for Egger's regression intercept and Begg rank correlation, respectively. The P value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the Clinical Scores Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG , MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell-therapy process (3). After injection through the tail vein or intra-peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti-inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund's adjuvant; MOG , myelin oligodendrocyte glycoprotein; MT, Mycobacterium tuberculosis; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.
Topics: Humans; Mice; Animals; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Anti-Inflammatory Agents; Macrophages; Mice, Inbred C57BL; Peptide Fragments
PubMed: 36300567
DOI: 10.1111/fcp.12844 -
Journal of Neurology, Neurosurgery, and... Jan 2023Rituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of rituximab in myelin oligodendrocyte glycoprotein antibody-associated disorders compared with neuromyelitis optica spectrum disorder: a systematic review and meta-analysis.
BACKGROUND
Rituximab (RTX) efficacy in patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disorders (MOGADs) is still poorly understood, though it appears to be lower than in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4-IgG+NMOSDs). The aim of this systematic review and meta-analysis is to assess the efficacy and safety profile of RTX in patients with MOGAD and to compare RTX efficacy between MOGAD and AQP4-IgG+NMOSD.
METHODS
We searched original English-language articles published between 2012 and 2021 in MEDLINE, Cochrane, Central Register of Controlled Trials and clinicaltrials.gov, reporting data on RTX efficacy in patients with MOGAD. The main outcome measures were annualised relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score mean differences (MDs) after RTX. The meta-analysis was performed with a random effects model. Covariates associated with the outcome measures were analysed with a linear meta-regression.
RESULTS
The systematic review included 315 patients (138 women, mean onset age 26.8 years) from 32 studies. Nineteen studies (282 patients) were included in the meta-analysis. After RTX, a significant decrease of ARR was found (MD: -0.92, 95% CI -1.24 to -0.60, p<0.001), markedly different from the AQP4-IgG+NMOSD (MD: -1.73 vs MOGAD -0.92, subgroup difference testing: Q=9.09, p=0.002). However, when controlling for the mean ARR pre-RTX, this difference was not significant. After RTX, the EDSS score decreased significantly (MD: -0.84, 95% CI -1.41 to -0.26, p=0.004). The frequency of RTX-related adverse events was 18.8% (36/192) and overall RTX-related mortality 0.5% (1/192).
CONCLUSIONS
RTX showed effective in MOGAD, although to a lesser extent than in AQP4-IgG+NMOSD, while the safety profile warrants some caution in its prescription. Randomised-controlled trials are needed to confirm these findings and provide robust evidence to improve treatment strategies in patients with MOGAD.
PROSPERO REGISTRATION NUMBER
CRD42020175439.
Topics: Female; Humans; Neuromyelitis Optica; Rituximab; Myelin-Oligodendrocyte Glycoprotein; Aquaporin 4; Recurrence; Immunoglobulin G; Autoantibodies
PubMed: 36283808
DOI: 10.1136/jnnp-2022-330086 -
Multiple Sclerosis and Related Disorders Dec 2022Myelin oligodendrocyte glycoprotein (MOG) antibodies mediate inflammatory demyelinating diseases of the central nervous system. This study aimed to understand the...
BACKGROUND
Myelin oligodendrocyte glycoprotein (MOG) antibodies mediate inflammatory demyelinating diseases of the central nervous system. This study aimed to understand the clinical characteristics of MOG antibody-associated aseptic meningitis (MOGAM).
METHODS
Here, we report the cases of two children with MOGAM. A systematic literature review was conducted and included patients who had MOGAM only, without neurological parenchymal lesions. The clinical characteristics that may have affected the outcome were statistically analyzed.
RESULTS
We reviewed 12 cases of MOGAM; male: female = 9: 3. Prolonged fever lasting over 7 days (11/12) was the most frequent symptom, followed by headache (10/12), vomiting (5/12), and seizures (4/12). None of the patients had focal neurological manifestations or parenchymal lesions on imaging. Cerebrospinal fluid (CSF) leukocytosis was observed in all patients (12/12), and blood leukocytosis and elevated CSF pressure was observed in all patients who had corresponding results (9/9 and 4/4, respectively). Seizures occurrence was lower than that of MOG antibody-associated cortical encephalitis. Seven cases progressed to other MOG antibody-associated diseases (MOGADs) in the later phase of MOGAM. Patients who did not progress to other MOGADs had a shorter disease duration from onset to the initiation of intravenous methylprednisolone than those who did. All the patients achieved full recovery after steroid treatment. One patient had relapses.
CONCLUSIONS
MOGAM without inflammatory demyelination is a rare but distinct phenotype of MOGAD, with fewer clinical manifestations mimicking bacterial or viral meningitis/encephalomeningitis. Delayed diagnosis and treatment may induce the progression to other severe MOGADs. Early recognition of this unique autoimmune aseptic meningitis may contribute to early diagnosis, treatment, and better outcomes.
Topics: Female; Humans; Male; Autoantibodies; Encephalitis; Meningitis, Aseptic; Myelin-Oligodendrocyte Glycoprotein; Seizures; Child
PubMed: 36115288
DOI: 10.1016/j.msard.2022.104126 -
Biomedicines Jun 2022Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic... (Review)
Review
Autoimmune pancreatitis (AIP) is a rare etiological type of chronic pancreatitis. The clinical and radiological presentation of AIP often resembles that of pancreatic cancer. Identifying non-invasive markers for their early distinction is of utmost importance to avoid unnecessary surgery or a delay in steroid therapy. Thus, this systematic review was conducted to revisit all current evidence on the clinical utility of different serum biomarkers in diagnosing AIP, distinguishing AIP from pancreatic cancer, and predicting disease course, steroid therapy response, and relapse. A systematic review was performed for articles published up to August 2021 by searching electronic databases such as MEDLINE, Web of Science, and EMBASE. Among 5123 identified records, 92 studies were included in the qualitative synthesis. Apart from immunoglobulin (Ig) G4, which was by far the most studied biomarker, we identified autoantibodies against the following: lactoferrin, carboanhydrase II, plasminogen-binding protein, amylase-α2A, cationic (PRSS1) and anionic (PRSS2) trypsinogens, pancreatic secretory trypsin inhibitor (PSTI/SPINK1), and type IV collagen. The identified novel autoantigens were laminin 511, annexin A11, HSP-10, and prohibitin. Other biomarkers included cytokines, decreased complement levels, circulating immune complexes, -glycan profile changes, aberrant miRNAs expression, decreased IgA and IgM levels, increased IgE levels and/or peripheral eosinophil count, and changes in apolipoprotein isoforms levels. To our knowledge, this is the first systematic review that addresses biomarkers in AIP. Evolving research has recognized numerous biomarkers that could help elucidate the pathophysiological mechanisms of AIP, bringing us closer to AIP diagnosis and its preoperative distinction from pancreatic cancer.
PubMed: 35884816
DOI: 10.3390/biomedicines10071511 -
Frontiers in Immunology 2022Anti--methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis... (Review)
Review
Anti--methyl-d-aspartate receptor encephalitis (NMDARe), a common autoimmune encephalitis, can be accompanied by demyelinating disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). To compare the clinical characteristics of patients with different overlapping syndromes, we searched the PubMed database and performed a systematic review. Of the 79 patients with overlapping syndromes, 15 had MS, 18 had aquaporin-4-antibody-positive NMOSD (AQP4-Ab-positive NMOSD), and 46 had MOGAD. Compared with classical NMDARe, overlapping syndromes showed atypical symptoms, such as limb weakness, sensory disturbance, and visual impairments in addition to the main symptoms of NMDARe and a lower ratio of ovarian teratoma. Patients with MOGAD overlap were the youngest, while patients with MS and AQP4-Ab-positive NMOSD overlap tended to be older than patients with classical NMDARe. A majority of patients with NMDARe who overlapped with MS or AQP4-Ab-positive NMOSD were female, but this was not the case for patients overlapped with MOGAD. When NMDARe and demyelinating diseases occurred sequentially, the interval was the longest in patients with NMDARe overlapped with MS. A favorable outcome was observed in patients overlapping with MOGAD, but no robust comparison can be drawn with the patients overlapping with AQP4-Ab-positive NMOSD and MS regarding the small number of available data. The long-term prognosis of overlapping syndromes needs further investigation.
Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Female; Humans; Male; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Neuromyelitis Optica; Receptors, N-Methyl-D-Aspartate
PubMed: 35837405
DOI: 10.3389/fimmu.2022.857443 -
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 -
Expert Opinion on Drug Safety Jul 2022The autoimmune-induced thyroid eye disease (TED) is a frequent extrathyroidal manifestation of Graves' disease and less frequently of Hashimoto's thyroiditis....
INTRODUCTION
The autoimmune-induced thyroid eye disease (TED) is a frequent extrathyroidal manifestation of Graves' disease and less frequently of Hashimoto's thyroiditis. Pathognomonic clinical signs, i.e. exophthalmos, double vision, and inflammation of the orbital tissue cause physical, ophthalmic, and socio-psychological limitations.
AREAS COVERED
PubMed and MeSH database were searched for specific guidelines, randomized controlled trials, prospective clinical studies, systematic reviews, and meta-analyses pertaining to the safety profile of currently administered immunosuppressive agents for the treatment of TED. Occurred adverse events (AE), severe AE (SAE), side effects (SE), and severe SE (SSE) were classified according to the standardized medical dictionary for regulatory activities (MedDRA).
EXPERT OPINION
This novel systematic analysis offers an overview of potential AE, SAE, and SE for currently recommended immunosuppressive drugs for the treatment of TED. Nonspecific, anti-inflammatory drugs and more specific, targeted biologicals are treatment options for active and severe TED. Critical evaluation of the pertinent literature confirms an evidence-based, beneficial efficacy/risk ratio of the current first-line and second-line treatment recommendations endorsed by the European Society of Endocrinology. However, further large, well-conceived trials are mandatory to enhance our knowledge and experience with novel specific small molecules and/or monoclonal antibodies targeting the key autoantigens in TED.
Topics: Antibodies, Monoclonal; Graves Disease; Graves Ophthalmopathy; Humans; Immunosuppressive Agents; Prospective Studies
PubMed: 35447047
DOI: 10.1080/14740338.2022.2069239 -
Nephrologie & Therapeutique Apr 2022The use of traditional immunosuppressive medicines for the treatment of membranous nephropathy is being challenged, owing to its limited efficacy and tolerability.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The use of traditional immunosuppressive medicines for the treatment of membranous nephropathy is being challenged, owing to its limited efficacy and tolerability. Research on M-type phospholipase A2 receptor antibodies has provided a new way for evaluating the efficiency and prognosis of treatment of membranous nephropathy. However, the relationship between rituximab, a monoclonal antibody against CD20, and antiphospholipase A2 receptor antibodies and the drug regimen of rituximab for membranous nephropathy is uncertain. We conducted a meta-analysis to evaluate the efficacy of rituximab treatments in membranous nephropathy and compared the clinical effects of first-line and second-line rituximab therapies.
METHODS
PubMed, Embase, Web of Science, Scopus, the Cochrane Central Register ofControlled Trials, and ClinicalTrials.gov were searched to find articles about rituximab treatment of patients with membranous nephropathy between January 2000 and August 2020. The outcomes included remission, antiphospholipase A2 receptor antibodies, relapse, and adverse events. The Grading of Recommendations Assessment Development and Evaluation criteria were used to evaluate the strength of evidence.
RESULTS
A total of 723 participants from 11 trials were included in this meta-analysis. The other treatments included cyclosporine, cyclophosphamide, steroids, and non-immunosuppressive antiproteinuric treatment. Rituximab significantly improved cumulative remission (P=0.007; Odds Ratio [OR]=3.06; 95% confidence interval [CI]=1.35-6.94) compared with other treatments. It significantly reduced relapse (P<0.00001; OR=0.06; 95% CI=0.02-0.19), antiphospholipase A2 receptor antibody levels (P=0.0009; SMD=-0.52; 95% CI=-0.83 to -0.21), and the proportion of patients positive for anti-PLA2R antibodies (P=0.003; OR=6.11; 95% CI=1.85-20.24) compared with other treatments. Compared with the second-line, first-line rituximab therapy achieved a higher rate of cumulative remission (P=0.03; OR=0.32, 95% CI=0.11-0.91).
CONCLUSIONS
Rituximab can improve the rate of clinical remission in patients with membranous nephropathy. Rituximab was more effective than other treatments in reducing relapse, antiphospholipase A2 receptor antibody levels, and the proportion of patients positive for antiphospholipase A2 receptor antibodies. The clinical remission rate following first-line rituximab therapy was better than that of second-line rituximab therapy for membranous nephropathy.
Topics: Autoantibodies; Autoantigens; Cyclophosphamide; Cyclosporine; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Receptors, Phospholipase A2; Recurrence; Rituximab
PubMed: 35074299
DOI: 10.1016/j.nephro.2021.10.002 -
Journal of Neuroimmunology Mar 2022Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD) is neuroimmunological disorder manifesting as episodes of ADEM, optic... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of rituximab for relapse prevention in myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD): A systematic review and meta-analysis.
INTRODUCTION
Myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG)-associated disorders (MOGAD) is neuroimmunological disorder manifesting as episodes of ADEM, optic neuritis, transverse myelitis, brainstem encephalitis, and other CNS manifestations and notably, distinct from multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Current treatment strategy is high-dose intravenous methylprednisolone followed by maintenance immunotherapy for relapse prevention. The purpose of this study is to systematically create compelling evidence addressing the role of rituximab in relapse prevention among patient with MOGAD.
METHODS
This study follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. We searched PubMed, Embase, and Google Scholar for English language papers published between 2010 and 2021. Individual study proportions were meta-analyzed to yield the pooled relapse-free patient proportion. Individual studies' mean pre- and post-treatment annualized relapse ratio (ARR) and Expanded Disability Status Scale (EDSS) were used to calculate the overall mean difference.
RESULTS
Our meta-analysis includes 13 studies with 238 subjects. After rituximab treatment, 55% (95% CI: 0.49-0.61) of MOGAD patients remained relapse-free. Our study found that after rituximab therapy, ARR was lowered by 1.36 (95% CI 1.02-1.71, p < 0.001). Similarly, we detected a 0.52 (95% CI: 0.08 to 0.96, p = 0.02) difference in EDSS score after starting rituximab medication. Because only a handful of the included studies documented adverse events, the safety profile of rituximab for the treatment of MOGAD could not be effectively determined.
CONCLUSION
Our meta-analysis shows that rituximab effectively prevents relapses in MOGAD patients.
Topics: Autoantibodies; Autoantigens; Demyelinating Autoimmune Diseases, CNS; Humans; Immunoglobulin G; Immunologic Factors; Myelin-Oligodendrocyte Glycoprotein; Recurrence; Rituximab
PubMed: 35063726
DOI: 10.1016/j.jneuroim.2022.577812