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RMD Open Feb 2024In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and...
BACKGROUND
In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), histopathological assessment of affected tissue is often necessary for diagnosis and assessment of disease extent. There is a requirement for validated non-invasive biomarkers to avoid the need for serial tissue biopsies.
METHODS
A systematic review of scientific databases from 2012 until present was performed to identify studies fulfilling the inclusion criteria. Studies were assessed for quality using the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cohort, case-control and cross-sectional studies and the Risk of Bias Assessment tool for Non-randomised Studies, or the Cochrane Risk of Bias tool 2.0 for randomised controlled trials. A descriptive synthesis of the data for non-invasive (blood-based or urinary) biomarkers of AAV-related disease activity and organ damage was performed.
RESULTS
Twenty-two high quality studies were included. These articles reported the value of blood-based and urinary biomarkers including anti-neutrophil cytoplasmic antibodies, immune cells, complement factors, gene expression profiles, cytokines, chemokines and other proteins in the assessment of disease activity and/or organ damage in patients with AAV. Many of these biomarkers involve the alternative complement pathway, neutrophil activation and macrophage activation.
CONCLUSION
This is the first contemporary systematic review synthesising the value of non-invasive biomarkers of AAV-related disease activity and organ damage. The incorporation of individual markers in combined biomarker profiles might enhance clinical decision-making. Many unmet needs were identified; few studies involve oeosinophilic granulomatosis with polyangiitis and patients with childhood-onset AAV. Further validation of the candidate biomarkers is warranted in large prospective studies to bridge the existing knowledge gaps and apply precision health to systemic vasculitis.
Topics: Humans; Child; Granulomatosis with Polyangiitis; Prospective Studies; Cross-Sectional Studies; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biomarkers; Antibodies, Antineutrophil Cytoplasmic; Cytokines
PubMed: 38341193
DOI: 10.1136/rmdopen-2023-003579 -
Thyroid : Official Journal of the... Mar 2024Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone... (Meta-Analysis)
Meta-Analysis
Hashimoto thyroiditis (HT) is the most common cause of hypothyroidism in iodine-sufficient areas. Selenium is an essential trace element required for thyroid hormone synthesis and exerts antioxidant effects. Therefore, it may be of relevance in the management of HT. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of selenium supplementation on thyroid function (thyrotropin [TSH], free and total thyroxine [fT4, T4], free and total triiodothyronine [fT3, T3]), thyroid antibodies (thyroid peroxidase antibodies [TPOAb], thyroglobulin antibodies [TGAb], thyrotropin receptor antibody [TRAb]), ultrasound findings (echogenicity, thyroid volume), immune markers, patient-reported outcomes, and adverse events in HT. The study protocol was registered on PROSPERO (CRD42022308377). We systematically searched MEDLINE, Embase, CINHAL, Web of Science, Google Scholar, and the Cochrane CENTRAL Register of Trials from inception to January 2023 and searched citations of eligible studies. Two independent authors reviewed and coded the identified literature. The primary outcome was TSH in patients without thyroid hormone replacement therapy (THRT); the others were considered secondary outcomes. We synthesized the results as standardized mean differences (SMD) or odds ratio (OR), assessed risk of bias using the Cochrane RoB 2 tool, and rated the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We screened 687 records and included 35 unique studies. Our meta-analysis found that selenium supplementation decreased TSH in patients without THRT (SMD -0.21 [confidence interval, CI -0.43 to -0.02]; 7 cohorts, 869 participants; = 0%). In addition, TPOAb (SMD -0.96 [CI -1.36 to -0.56]; 29 cohorts; 2358 participants; = 90%) and malondialdehyde (MDA; SMD -1.16 [CI -2.29 to -0.02]; 3 cohorts; 248 participants; = 85%) decreased in patients with and without THRT. Adverse effects were comparable between the intervention and control groups (OR 0.89 [CI 0.46 to 1.75]; 16 cohorts; 1339 participants; = 0%). No significant changes were observed in fT4, T4, fT3, T3, TGAb, thyroid volume, interleukin (IL)-2, and IL-10. Overall, certainty of evidence was moderate. In people with HT without THRT, selenium was effective and safe in lowering TSH, TPOAb, and MDA levels. Indications for lowering TPOAb were found independent of THRT.
Topics: Humans; Autoantibodies; Dietary Supplements; Hashimoto Disease; Randomized Controlled Trials as Topic; Selenium; Thyrotropin
PubMed: 38243784
DOI: 10.1089/thy.2023.0556 -
Cellular & Molecular Biology Letters Jan 2024Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine...
Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease's systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials.
Topics: Humans; Adenosine; Adenosine Deaminase; Arthritis, Rheumatoid; Inflammation; Quercetin; Adenosine Deaminase Inhibitors
PubMed: 38225555
DOI: 10.1186/s11658-024-00531-7 -
Medicine Dec 2023Hashimoto's thyroiditis (HT) is the prevailing form of autoimmune thyroiditis and the leading cause of hypothyroidism in iodine-sufficient regions worldwide. This study... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hashimoto's thyroiditis (HT) is the prevailing form of autoimmune thyroiditis and the leading cause of hypothyroidism in iodine-sufficient regions worldwide. This study aims to evaluate the efficacy of vitamin D supplementation on HT through a meta-analysis of randomized controlled trials (RCTs).
METHODS
The databases searched included PubMed, and others. We included RCTs that the treatment group received vitamin D, while the control group received either a placebo or no treatment. The studies measured the baseline and endpoint levels of 25-hydroxyvitamin D [25(OH)D], thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), anti-thyroid peroxidase antibody (TPO-Ab), and thyroglobulin antibody (TG-Ab). We performed a meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval (CI).
RESULTS
A total of 12 studies involving 862 individuals were included. Vitamin D supplementation has a significant impact on reducing the titers of TPO-Ab (SMD = -1.084, 95% CI = -1.624 to -0.545) and TG-Ab (SMD = -0.996, 95% CI = -1.579 to -0.413) in patients with HT, and it also improves thyroid function by decreasing TSH level (SMD = -0.167, 95% CI = -0.302 to 0.031) and increasing FT3 (SMD = 0.549, 95% CI = 0.077-1.020) and FT4 (SMD = 0.734, 95% CI = 0.184-1.285) levels. Active vitamin D (calcitriol) significantly reduces the titer of TPO-Ab compared to naive forms of vitamin D (vitamin D2 or D3); treatment durations > 12 weeks result in a more effective reduction of TPO-Ab levels and a more significant increase in FT4 and FT3 levels in patients with HT (meta-regression P < .05).
CONCLUSION
Vitamin D supplementation may have beneficial effects on HT patients by modulating immune responses and improving thyroid function.
Topics: Humans; Autoantibodies; Dietary Supplements; Hashimoto Disease; Thyrotropin; Vitamin D
PubMed: 38206745
DOI: 10.1097/MD.0000000000036759 -
Gastroenterology Apr 2024Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Current international guidelines recommend duodenal biopsies to confirm the diagnosis of celiac disease in adult patients. However, growing evidence suggests that immunoglobulin A (IgA) anti-tissue transglutaminase (tTg) antibody levels ≥10 times the upper limit of normal (ULN) can accurately predict celiac disease, eliminating the need for biopsy. We performed a systematic review and meta-analysis to evaluate the accuracy of the no-biopsy approach to confirm the diagnosis of celiac disease in adults.
METHODS
We systematically searched MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1998 to October 2023 for studies reporting the sensitivity and specificity of IgA-tTG ≥10×ULN against duodenal biopsies (Marsh grade ≥2) in adults with suspected celiac disease. We used a bivariate random effects model to calculate the summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The positive and negative likelihood ratios were used to calculate the positive predictive value of the no-biopsy approach across different pretest probabilities of celiac disease. The methodological quality of the included studies was evaluated using the QUADAS-2 tool. This study was registered with PROSPERO, number CRD42023398812.
RESULTS
A total of 18 studies comprising 12,103 participants from 15 countries were included. The pooled prevalence of biopsy-proven celiac disease in the included studies was 62% (95% confidence interval [CI], 40%-83%). The proportion of patients with IgA-tTG ≥10×ULN was 32% (95% CI, 24%-40%). The summary sensitivity of IgA-tTG ≥10×ULN was 51% (95% CI, 42%-60%), and the summary specificity was 100% (95% CI, 98%-100%). The area under the summary receiver operating characteristic curve was 0.83 (95% CI, 0.77 - 0.89). The positive predictive value of the no-biopsy approach to identify patients with celiac disease was 65%, 88%, 95%, and 99% if celiac disease prevalence was 1%, 4%, 10%, and 40%, respectively. Between-study heterogeneity was moderate (I =30.3%), and additional sensitivity analyses did not significantly alter our findings. Only 1 study had a low risk of bias across all domains.
CONCLUSION
The results of this meta-analysis suggest that selected adult patients with IgA-tTG ≥10×ULN and a moderate to high pretest probability of celiac disease could be diagnosed without undergoing invasive endoscopy and duodenal biopsy.
Topics: Adult; Humans; Celiac Disease; Transglutaminases; Protein Glutamine gamma Glutamyltransferase 2; Immunoglobulin A; GTP-Binding Proteins; Biopsy; Sensitivity and Specificity; Autoantibodies
PubMed: 38176661
DOI: 10.1053/j.gastro.2023.12.023 -
International Journal of Molecular... Dec 2023Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This... (Review)
Review
Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases that widely spread and share the same patterns of pro-inflammatory cytokines. This systematic review aims to evaluate the effects of non-surgical periodontal treatment (NSPT) on RA and, conversely, the impact of disease-modifying anti-rheumatic drugs (DMARDs) on periodontitis. PubMed, Embase, and Web of Science were searched using the MESH terms "periodontitis" and "rheumatoid arthritis" from January 2012 to September 2023. A total of 49 articles was included in the final analysis, 10 of which were randomized controlled trials. A total of 31 records concerns the effect of NSPT on parameters of RA disease activity, including a 28-joint disease activity score, anti-citrullinated protein antibodies, rheumatoid factor, C reactive protein, erythrocyte sedimentation rate, pro-inflammatory cytokines and acute phase proteins in serum, saliva, gingival crevicular fluid, and synovial fluid. A total of 18 articles investigated the effect of DMARDs on periodontal indexes and on specific cytokine levels. A quality assessment and risk-of-bias of the studies were also performed. Despite some conflicting results, there is evidence that RA patients and periodontitis patients benefit from NSPT and DMARDs, respectively. The limitations of the studies examined are the small samples and the short follow-up (usually 6 months). Further research is mandatory to evaluate if screening and treatment of periodontitis should be performed systematically in RA patients, and if the administration of DMARDs is useful in reducing the production of cytokines in the periodontium.
Topics: Humans; Antirheumatic Agents; Periodontitis; Arthritis, Rheumatoid; Rheumatoid Factor; Cytokines
PubMed: 38139057
DOI: 10.3390/ijms242417228 -
Medicine Dec 2023To investigate the risk factors for the development of pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE). (Meta-Analysis)
Meta-Analysis
BACKGROUND
To investigate the risk factors for the development of pulmonary arterial hypertension (PAH) in patients with systemic lupus erythematosus (SLE).
METHODS
The literature related to risk factors for the development of PAH in SLE patients was searched by the computer on China national knowledge infrastructure (CNKI), PubMed, and Embase, and the literature search was limited to the period of library construction to October 2022. Two researchers independently performed literature screening and literature information extracting, including first author, publication time, case collection time, sample size, and study factors, and used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the literature. The relationship between each clinical manifestation and laboratory index and the occurrence of PAH in SLE patients was evaluated based on the ratio (OR value) and its 95% CI.
RESULTS
A total of 24 publications were included, including 23 case-control studies and 1 cohort study with NOS ≥ 6, and the overall quality of the literature was high. The risk of PAH was higher in SLE patients who developed Raynaud phenomenon than in those who did not [OR = 2.39, 95% CI (1.91, 2.99), P < .05]; the risk of PAH was higher in SLE patients who were positive for anti-RNP antibodies than in those who were negative for anti-RNP antibodies [OR = 1.77, 95% CI (1.17, 3.2.65), P < .05]; the risk of PAH was higher in SLE patients with interstitial lung lesions than in those without combined interstitial lung lesions [OR = 3.28, 95% CI (2.37, 4.53), P < .05]; the risk of PAH was higher in SLE patients with combined serositis than in those without serositis [OR = 2.28, 95% CI (1.83, 2.84), P < .05]. The risk of PAH was higher in SLE patients with combined pericardial effusion than in those without pericardial effusion [OR = 2.97, 95% CI (2.37, 3.72), P < .05]; the risk of PAH was higher in SLE patients with combined vasculitis than in those without vasculitis [OR = 1.50, 95% CI (1.08, 2.07), P < .05]; rheumatoid factor-positive SLE patients had a higher risk of PAH than those with rheumatoid factor-negative [OR = 1.66, 95% CI (1.24, 2.24), P < .05].
CONCLUSION
Raynaud phenomenon, vasculitis, anti-RNP antibodies, serositis, interstitial lung lesions, rheumatoid factor, and pericardial effusion are risk factors for the development of PAH in patients with SLE.
Topics: Humans; Pulmonary Arterial Hypertension; Cohort Studies; Hypertension, Pulmonary; Serositis; Pericardial Effusion; Rheumatoid Factor; Lupus Erythematosus, Systemic; Familial Primary Pulmonary Hypertension; Risk Factors; Raynaud Disease; Vasculitis
PubMed: 38134088
DOI: 10.1097/MD.0000000000036654 -
Encephalitis (Seoul, Korea) Jan 2024Neurological complications related to coronavirus disease 2019 (COVID-19) infection have been increasingly reported. One of the most serious neurological complications...
Neurological complications related to coronavirus disease 2019 (COVID-19) infection have been increasingly reported. One of the most serious neurological complications is encephalitis, which could be due either to direct viral invasion or an immune-mediated inflammatory reaction. In this study, we conducted a systematic review of reported cases of autoimmune encephalitis mediated by N-methyl-ᴅ-aspartate receptor antibodies in conjunction with or after diagnosis of COVID-19 infection.
PubMed: 38126079
DOI: 10.47936/encephalitis.2023.00171 -
RMD Open Dec 2023Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing...
OBJECTIVE
Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing reported data on the CD38-targeting antibody daratumumab as a new therapeutic approach in autoantibody-mediated autoimmune diseases.
METHODS
A protocolised systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases (Medline and Embase) were searched for suitable studies. Usage of daratumumab in non-oncological or non-transplantation associated diseases with autoimmune pathophysiology was analysed including patient characteristics, therapeutic regimen, adverse events and patient outcome.
RESULTS
38 publications reporting the clinical course of 83 patients met the inclusion criteria. Daratumumab usage was reported in therapy-refractory cases (median of 5 different previous therapies) in 24 different autoimmune diseases. The median number of applications of daratumumab was 4, mainly via intravenous applications (87%). Concomitant treatment included glucocorticoids in 64% of patients, intravenous immunoglobulins (33%) and rituximab (17%). Remission or improvement of disease was reported in 81% of patients. Autoantibody depletion or reduction was stated in 52% of patients. Death occurred in three patients (3%). Adverse events were reported in 45% of patients including application-associated reaction (20%), infection (19%) and hypogammaglobulinaemia (33%).
CONCLUSION
Targeting CD38 via daratumumab is a new promising therapeutic option in therapy refractory autoimmune diseases. Efficacy as well as optimal therapeutic regimen and management or prevention of adverse events require further investigation. Therefore, systematic clinical trials of this therapeutic approach are needed.
Topics: Humans; Antibodies, Monoclonal; Rituximab; Autoimmune Diseases; Autoantibodies
PubMed: 38101819
DOI: 10.1136/rmdopen-2023-003604 -
BMJ Open Respiratory Research Nov 2023Interstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Interstitial lung disease (ILD) is an important manifestation of autoimmune diseases that can lead to morbidity and mortality. Although several autoantibodies have been linked with ILD presentation and adverse outcomes, the association of anti-Ro52 antibody with ILD is less studied. Hence, we investigated this association in various autoimmune diseases in the current study.
DESIGN
We designed a systematic review and meta-analysis and did a comprehensive search from inception until 2 January 2023.
DATA SOURCES
A systematic search was conducted in four electronic databases: PubMed, Web of Science, Scopus and Embase.
ELIGIBILITY CRITERIA
Observational studies that reported ILD diagnosis (outcome) and anti-Ro antibody (exposure) status in any autoimmune conditions (population) were included. The association between rapidly progressive ILD (RP-ILD) and anti-Ro52 was studied in idiopathic inflammatory myopathies (IIM).
DATA EXTRACTION AND SYNTHESIS
Collected data included study characteristics and ORs with 95% CIs. Quality assessment was performed using a modified version of the Newcastle-Ottawa Scale for cross-sectional studies. Random effects meta-analysis was used to pool the effect estimates.
RESULTS
A total of 2353 studies were identified, from which 59 articles met the eligibility criteria. Anti-Ro52/SSA positivity was associated with ILD in all autoimmune disease subgroups: IIM (OR=3.08; 95% CI: 2.18 to 4.35; p value<0.001; I=49%), systemic lupus (OR=2.43; 95% CI: 1.02 to 5.79; p=0.046; I=71%), Sjogren (OR=1.77; 95% CI: 1.09 to 2.87; p=0.021; I=73%), systemic sclerosis (OR=1.71; 95% CI: 1.04 to 2.83; p=0.036; I=43%), mixed connective tissue disease (OR=3.34; 95% CI: 1.82 to 6.13; p<0.001; I=0%). Additionally, anti-Ro52-positive myopathy patients were more likely to have simultaneous RP-ILD (OR=2.69; 95% CI:1.50 to 4.83; p<0.001; I=71%).
CONCLUSION
Anti-Ro52/SSA positivity is associated with a higher frequency of ILD diagnosis in various autoimmune diseases. Anti-Ro52/SSA is also linked with a more severe lung involvement (RP-ILD). Future studies can investigate the benefits of screening for anti-Ro52 and its association with ILD development.
PROSPERO REGISTRATION NUMBER
CRD42022381447.
Topics: Humans; Autoantibodies; Cross-Sectional Studies; Autoimmune Diseases; Lung Diseases, Interstitial; Scleroderma, Systemic; Myositis
PubMed: 38030264
DOI: 10.1136/bmjresp-2023-002076