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Human Reproduction Update 2014Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Increasing numbers of children are being conceived by assisted reproductive technology (ART). A number of studies have highlighted an altered epigenetic status in gametes from infertile couples and the possibility of an increased risk of imprinting defects and somatic epigenetic changes in ART conceived children, but the results have been heterogeneous. We performed a systematic review of existing studies to compare the incidence of imprinting disorders and levels of DNA methylation in key imprinted genes in children conceived through in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with those in children conceived spontaneously.
METHODS
A detailed search strategy was used to conduct electronic literature searches (spanning 1978 to 2013) on Medline, EMBASE, the Cochrane Library and Web of Science. Abstracts of relevant conference papers were identified. As randomized trials are not feasible in this context, we included observational (cohort and case-control) studies comparing outcomes in children conceived through ART with those conceived spontaneously, irrespective of the language of publication. The outcome measures were DNA methylation and the incidence of imprinting disorders.
RESULTS
A total of 351 publications were identified by the initial search. Of these, 26 were excluded as duplicates and 241 were excluded after reviewing the abstracts, then of those remaining 66 were excluded after review of the full text. A total of 18 papers were included in the review. Apart from one case-control study, all were cohort studies. There was a degree of clinical heterogeneity in terms of the study population, type of infertility treatment, and samples obtained from exposed and unexposed children. DNA methylation levels were either presented as categorical data (hypo-, hyper- or normally methylated DNA) or continuous data (i.e. percentage of methylated DNA). The combined odds ratio (95% confidence intervals) of any imprinting disorder in children conceived through ART was 3.67 (1.39, 9.74) in comparison with spontaneously conceived children. Meta-analysis of data from relevant studies revealed that the weighted mean difference (95% confidence intervals) in methylation percent between IVF/ICSI versus spontaneously conceived children were as follows: H19: -0.46(-1.41, 0.49), PEG1-MEST: 0.47 (-2.07, 3.01), GRB10: -0.05 (-0.43, 0.33), IGF2: -0.15 (-1.09, 0.79), SNRPN: -0.55 (-1.55, 0.46), KvDMR/KCNQ10T1: -0.16 (-0.34, 0.02) and PEG3: -0.24 (-1.72, 1.24).
CONCLUSIONS
There was an increase in imprinting disorders in children conceived though IVF and ICSI but insufficient evidence for an association between ART and methylation in other imprinted genes. Heterogeneity in the types of fertility treatment, the imprinted regions studied, the tissues used and the methods of measurement, reduce our ability to assess the full effect of ART on DNA methylation and imprinting. More controlled studies, using standardized methodologies, in larger, better clinically defined populations are needed.
Topics: Child; Cohort Studies; DNA Methylation; Fertilization in Vitro; GRB10 Adaptor Protein; Genomic Imprinting; Humans; Infertility; Potassium Channels, Voltage-Gated; Proteins; RNA, Long Noncoding; Sperm Injections, Intracytoplasmic; snRNP Core Proteins
PubMed: 24961233
DOI: 10.1093/humupd/dmu033 -
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 -
Seminars in Arthritis and Rheumatism Apr 2020ImmunoglobulinG4-related disease (IgG4-RD) is a recently recognized disease and, as such, there is a pressing need to identify biomarkers for diagnosis, monitoring...
OBJECTIVE
ImmunoglobulinG4-related disease (IgG4-RD) is a recently recognized disease and, as such, there is a pressing need to identify biomarkers for diagnosis, monitoring disease activity, and predicting prognosis and response to therapy. Here, we review the recent development and identification of biomarkers for IgG4-RD.
METHODS
Through extensive literature review and analysis, we updated the biomarkers for IgG4-RD and further put forward our own viewpoints.
RESULTS
In addition to traditional biomarkers, such as serum IgG4 concentration and typical histological characteristics, several novel indicators, including IgG2, serum soluble IL-2 receptor (sIL2R), and cc-chemokine ligand 18 (CCL18), indicate inflammation and fibrosis and can be used to accurately diagnose and predict treatment response. Studies to identify target autoantigens in IgG4-RD have shed light on the unmet need for biomarkers that can identify this disorder. Additionally, both serological and histopathologic immune cells involved in antigen-induced responses, innate immune cells (macrophages, mast cells, and the I-IFN/ IL-33 pathway), as well as subsequent acquired immune cells (T and B cell subsets), may also serve as new biomarkers for IgG4-RD. Since IgG4-RD often clinically manifests with multiple organs involvement, non-invasive PET-CT can improve diagnosis and antidiastole levels.
CONCLUSION
These novel biomarkers provide information to help diagnose IgG4-RD, monitor disease activity, as well as predict prognosis and response to therapy.
Topics: Biomarkers; Chemokines, CC; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Receptors, Interleukin-2
PubMed: 31280934
DOI: 10.1016/j.semarthrit.2019.06.018 -
Journal of Affective Disorders Jul 2016While thyroid autoantibodies have been linked to depression in general population samples, it is unclear if the immunological milieu of pregnancy alters this... (Review)
Review
BACKGROUND
While thyroid autoantibodies have been linked to depression in general population samples, it is unclear if the immunological milieu of pregnancy alters this association. As a result, we systematically reviewed the literature to determine if abnormal levels of autoantibodies that target thyroperoxidase (TPO-AB) during the perinatal period are associated with an increased risk of antenatal and postnatal depression.
METHODS
MEDLINE, EMBASE, PsycINFO, and CINAHL databases were searched through February 2016. Primary studies that examined TPO-AB titers during pregnancy or the postpartum period, and antenatal or postnatal depression were eligible. The quality of each study was assessed using the Newcastle-Ottawa Scale.
RESULTS
Among the eleven articles selected for synthesis, three of these examined associations between TPO-AB and depression both during pregnancy and in the postpartum period. Three of five studies reported statistically significant associations between elevated TPO-AB titers (TPO-AB+) and concurrent depression at 12-25 weeks gestation. Four of five studies found significant associations between TPO-AB+ status at 12-25 weeks gestation and depression in the postpartum period. Two of four studies found links between postpartum TPO-AB and depression concurrently in the puerperium.
LIMITATIONS
Lack of adjustment for confounding variables limits causal inference and conclusions about the predictive power of TPO-AB.
CONCLUSIONS
Studies suggest that TPO-AB+ in early to mid-pregnancy is associated with concurrent depression and may be predictive of depression in the postpartum period. Future studies with improved methodology are required to better understand the full pathophysiological implications and predictive utility of TPO-AB in perinatal depression.
Topics: Autoantibodies; Autoantigens; Depression; Depression, Postpartum; Female; Humans; Iodide Peroxidase; Iron-Binding Proteins; Pregnancy; Risk Factors
PubMed: 27011366
DOI: 10.1016/j.jad.2016.03.021 -
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 -
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 -
Lupus Nov 2017Objective This article aims to determine the serological biomarkers which can be considered as risk factors of systemic lupus erythematosus (SLE)-associated pulmonary... (Meta-Analysis)
Meta-Analysis Review
Objective This article aims to determine the serological biomarkers which can be considered as risk factors of systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension by a systematic review and meta-analysis. Methods This study was conducted in accordance with the PRISMA statement. The search database included MEDLINE, EMBASE, Cochrane Library and Scopus. The Newcastle-Ottawa scale was used for the quality assessment. The odds ratio was the primary measure of effect of the risk factors. Results Twelve studies were included in this meta-analysis. The results identified the anti-RNP antibody and anti-Sm antibody as risk factors for SLE-associated pulmonary arterial hypertension with the pooled odds ratios 3.68 (95% confidence interval 2.04-6.63, P < 0.0001) and 1.71 (95% confidence interval 1.06-2.76, P = 0.03), respectively. Conclusion Pulmonary arterial hypertension is a serious complication of SLE with a worse prognosis than SLE patients without pulmonary arterial hypertension. The early recognition of pulmonary arterial hypertension with transthoracic echocardiography routinely performed in SLE patients with risk factors is necessary, especially in Asian patients.
Topics: Autoantibodies; Biomarkers; DNA; Humans; Hypertension, Pulmonary; Lupus Erythematosus, Systemic; Ribonucleoproteins; Risk Factors; snRNP Core Proteins
PubMed: 28409522
DOI: 10.1177/0961203317702255 -
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 -
Multiple Sclerosis and Related Disorders Jul 2020Recent reports have suggested that seizures may be a component of the clinical presentation in myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Recent reports have suggested that seizures may be a component of the clinical presentation in myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease. We aimed to conduct a systematic review and meta-analysis to comprehensively evaluate the occurrence of epileptic seizures in the disease.
METHODS
We searched PubMed, MEDLINE and EMBASE for studies reporting the occurrence of acute symptomatic seizures in MOG-Ab-associated disease. Fixed or random effects model was used to pool results across studies with a meta-analysis.
RESULTS
A total of 14 studies met the inclusion criteria. Overall, acute symptomatic seizures were observed in 20.5% (95% confidence interval [CI] 13.7%-30.7%, I=60.6%) patients with MOG-Ab-associated disease, and in a similar proportion of children respectively (20.0%; 95% CI 14.3%-27.8%, I=7.0%). The pooled probability of seizure occurrence in males was 30.1% (95% CI 17.5%-52%, I=0.0%) while that in females was much lower (12.0%; 95% CI 5.5%-26.4%, I=0.0%). Furthermore, when we focused on those with acute disseminated encephalomyelitis-like phenotype, 37.3% patients experienced seizures (95% CI 21.0%-66.3%, I=55.8%).
CONCLUSIONS
Our study suggested that epileptic seizures were common in MOG-Ab-associated disease and offered insight into associated factors that contribute to the occurrence of seizures. Future studies with explicit evaluation are required.
Topics: Autoantibodies; Child; Encephalomyelitis, Acute Disseminated; Epilepsy; Female; Humans; Male; Myelin-Oligodendrocyte Glycoprotein; Seizures
PubMed: 32222694
DOI: 10.1016/j.msard.2020.102057 -
Multiple Sclerosis and Related Disorders Nov 2021Aim to perform a systematic review of the literature on treatment of paediatric patients with MOG-IgG associated disease (MOGAD). Method We followed the guidelines of... (Review)
Review
Aim to perform a systematic review of the literature on treatment of paediatric patients with MOG-IgG associated disease (MOGAD). Method We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The search was conducted in Pubmed (MEDLINE) seeking articles of treatment of MOGAD in patients ≤ 18 years published between January 2012 and April 25th, 2020. Results We found 72 non-controlled studies (observational studies, case reports and expert recommendations). There were no randomized controlled trials (RCTs). The most commonly reported acute phase treatment was intravenous methylprednisolone in 88% followed by oral steroids in 67%, intravenous human immunoglobulin (IVIG) in 66% and plasma exchange in 33% of the studies. Long-term maintenance treatment was described by 53 studies mainly in relapsing disease course. The most frequently reported treatments were prolonged oral corticosteroids in 53% of the studies followed by azathioprine (51%), mycophenolate mofetil (45%), rituximab (41%) and periodic intravenous immunoglobulin (26%). Interpretation long-term treatment was reported mainly in relapsing MOGAD paediatric patients. However, the most frequently used medications are not those that have shown higher reduction in the annualised relapse rate in observational studies. RCTs with standardized outcomes are needed to confirm the safety and efficacy of current and new treatments.
Topics: Autoantibodies; Azathioprine; Child; Humans; Immunoglobulins, Intravenous; Myelin-Oligodendrocyte Glycoprotein; Plasmapheresis
PubMed: 34450460
DOI: 10.1016/j.msard.2021.103216