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Nutrients Nov 2023Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The... (Meta-Analysis)
Meta-Analysis Review
Iron deficiency (ID) is the most prevalent nutritional deficiency worldwide. Low levels of serum ferritin (SF) could affect the thyroid gland and its functioning. The purpose of this systematic review and meta-analysis is to summarize the main currently available evidence and analyze data on the relationship between ID and thyroid function. This study included all articles evaluating the relationship between ID and thyroid function. Quality assessment was performed using Cambridge Quality Checklists. The search strategy included the following combination of Medical Subjects Headings terms and keywords: "iron deficiency", "thyroid function", "thyroid disease", "thyroid dysfunction", and "hypothyroidism". A meta-analysis was performed to evaluate whether thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels differed between patients with ID and healthy controls without ID. For statistical comparison between cases and controls, the mean difference (MD) was calculated, and a subgroup analysis of pregnant and non-pregnant women was performed. Cochran's Q testing and heterogeneity indices () were used to assess statistical heterogeneity. Sensitivity analysis and publication bias analyses were also performed, both qualitatively and quantitatively. Finally, a meta-regression analysis was performed to evaluate the correlation between serum TSH or FT4 levels and SF in the study population. Ten cross-sectional studies were identified and reviewed. Patients with ID showed TSH (MD: -0.24 mIU/L; 95% CI -0.41, -0.07; = 100%, = 0.005), FT4 (MD: -1.18 pmol/L; 95% CI -1.43, -0.94; = 99%, < 0.000001), and FT3 (MD: -0.22 pmol/L; 95% CI -0.32, -0.12; = 99%, < 0.00001) levels that were significantly lower. Subgroup analysis confirmed significantly lower TSH, FT4, and FT3 levels in pregnant women. Non-pregnant women showed significantly lower serum FT4 and FT3 levels but no difference in TSH values. Meta-regression analysis showed that serum TSH and FT4 levels were positively correlated with SF levels. Our systematic review of the literature found that ID significantly increases the prevalence of thyroid autoantibody (anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies) positivity both individually and collectively. Studies currently published in the literature indicate a possible relationship between ID, thyroid function, and autoimmunity, especially in some patient groups. Data analysis shows that thyroid hormone levels are lower in patients with ID and, in particular, in pregnant women. Further studies are needed to understand the role played by iron in thyroid metabolism.
Topics: Humans; Female; Pregnancy; Thyroxine; Thyroid Function Tests; Cross-Sectional Studies; Thyroid Hormones; Thyroid Diseases; Thyrotropin; Iron Deficiencies
PubMed: 38004184
DOI: 10.3390/nu15224790 -
Frontiers in Endocrinology 2023Hashimoto's thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hashimoto's thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other gluten-related conditions (GRC). In the last years, interest about gluten-free diet (GFD) has increased for its supposed extraintestinal anti-inflammatory effect; thus, many patients with HT initiate GFD on their own.
OBJECTIVES
The aim of this meta-analysis is to examine all available data in literature about the effect of a GFD on TgAb, TPOAb, TSH, FT4, and FT3 levels in patients with HT and no symptoms or histology of CD.
METHODS
The study was conducted according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology). The search was performed on databases PubMed and Scopus. The last search was performed on 7 February 2023. Quality assessment was performed. Meta-analyses were performed using the random-effect model. Hedges' was used to measure the effect size (ES). Statistical analyses were performed using StataSE 17.
RESULTS
The online search retrieved 409 articles, and 4 studies with a total of 87 patients were finally included for quantitative analysis. The risk of bias was generally low. The mean period of GFD was almost 6 months. The meta-analyses showed reduction in antibody levels with ES: -0.39 for TgAb (95% CI: -0.81 to +0.02; = 0.06; ² = 46.98%) and -0.40 for TPOAb (95% CI: -0.82 to +0.03; = 0.07; ² = 47.58%). TSH showed a reduction with ES: -0.35 (95% CI: -0.64 to -0.05; = 0.02; ² = 0%) and FT4 showed an increase with ES: +0.35% (95% CI: 0.06 to 0.64; = 0.02; ² = 0%). FT3 did not display variations (ES: 0.05; 95% CI: -0.38 to +0.48; = 0.82; ² = 51%). The heterogeneity of TgAb, TPOAb, and FT3 data was solved performing sub-analyses between patients with or without GRC (TgAb = 0.02; TPOAb = 0.02; FT3 = 0.04) and only for FT3, performing a sub-analysis between patients taking and not taking LT4 ( = 0.03).
CONCLUSION
This is the first meta-analysis investigating the effect of GFD on HT. Our results seem to indicate a positive effect of the gluten deprivation on thyroid function and its inflammation, particularly in patients with HT and GRC. However, current lines of evidence are not yet sufficient to recommend this dietary approach to all patients with a diagnosis of HT.
Topics: Humans; Thyroiditis, Autoimmune; Diet, Gluten-Free; Celiac Disease; Autoantibodies; Hashimoto Disease; Thyrotropin
PubMed: 37554764
DOI: 10.3389/fendo.2023.1200372 -
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 -
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 -
Cardiovascular Diabetology Nov 2023There is uncertainty regarding the role of obesity in type 1 diabetes development. The aim of this systematic review and meta-analysis was to collect and synthesize... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is uncertainty regarding the role of obesity in type 1 diabetes development. The aim of this systematic review and meta-analysis was to collect and synthesize evidence regarding BMI and the risk of developing type 1 diabetes.
METHODS
A systematic review and meta-analysis were conducted to assess the association between BMI and incident type 1 diabetes. Databases were searched up to June 2022. Cohort studies were included reporting the association between overweight and/or obesity, as measured by BMI after age 2 years, with incident type 1 diabetes. Independent reviewers extracted data and assessed study quality. Risk estimates were pooled using a random-effects model.
RESULTS
Ten cohort studies met the inclusion criteria. The seven studies that classified BMI into categories were of high quality and involved 1,690,660 individuals and 1979 incident type 1 diabetes cases. The pooled risk ratio (RR) for type 1 diabetes was 1.35 (95% CI 0.93-1.97) among people with overweight (3 studies); 2.17 (95% CI 1.75-2.69) among people with obesity (5 studies); and 1·87 (95% CI 1.52-2.29) among people with overweight/obesity (two studies merged the categories). These point estimates persisted in sensitivity analyses that addressed the duration of follow-up, variability in baseline risk for incident type 1 diabetes, and potential misclassifications related to exposure or outcome definitions. People with overweight/obesity had a 2.55 (95% CI 1.11-5.86) greater risk for incident type 1 diabetes with positive islet autoantibodies.
CONCLUSION
This systematic review and meta-analysis of high-quality observational cohort studies indicated an association between high BMI and the risk of type 1 diabetes, in a graded manner.
Topics: Humans; Child, Preschool; Overweight; Diabetes Mellitus, Type 1; Body Mass Index; Obesity; Cohort Studies
PubMed: 37919779
DOI: 10.1186/s12933-023-02007-y -
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 -
Journal of Stroke and Cerebrovascular... Nov 2023Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke diagnosis is dependent on lengthy clinical and neuroimaging assessments, while rapid treatment initiation improves clinical outcome. Currently, more sensitive biomarker assays of both non-coding RNA- and protein biomarkers have improved their detectability, which could accelerate stroke diagnosis. This systematic review and meta-analysis compares non-coding RNA- with protein biomarkers for their potential to diagnose and differentiate acute stroke (subtypes) in (pre-)hospital settings.
METHODS
We performed a systematic review and meta-analysis of studies evaluating diagnostic performance of non-coding RNA- and protein biomarkers to differentiate acute ischemic and hemorrhagic stroke, stroke mimics, and (healthy) controls. Quality appraisal of individual studies was assessed using the QUADAS-2 tool while the meta-analysis was performed with the sROC approach and by assessing pooled sensitivity and specificity, diagnostic odds ratios, positive- and negative likelihood ratios, and the Youden Index.
SUMMARY OF REVIEW
112 studies were included in the systematic review and 42 studies in the meta-analysis containing 11627 patients with ischemic strokes, 2110 patients with hemorrhagic strokes, 1393 patients with a stroke mimic, and 5548 healthy controls. Proteins (IL-6 and S100 calcium-binding protein B (S100B)) and microRNAs (miR-30a) have similar performance in ischemic stroke diagnosis. To differentiate between ischemic- or hemorrhagic strokes, glial fibrillary acidic protein (GFAP) levels and autoantibodies to the NR2 peptide (NR2aAb, a cleavage product of NMDA neuroreceptors) were best performing whereas no investigated protein or non-coding RNA biomarkers differentiated stroke from stroke mimics with high diagnostic potential.
CONCLUSIONS
Despite sampling time differences, circulating microRNAs (< 24 h) and proteins (< 4,5 h) perform equally well in ischemic stroke diagnosis. GFAP differentiates stroke subtypes, while a biomarker panel of GFAP and UCH-L1 improved the sensitivity and specificity of UCH-L1 alone to differentiate stroke.
Topics: Humans; Hemorrhagic Stroke; Stroke; Biomarkers; Ischemic Stroke; Glial Fibrillary Acidic Protein; MicroRNAs; RNA, Untranslated
PubMed: 37778160
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107388 -
RMD Open Aug 2023The first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The first biomarker associated with the rheumatoid arthritis is rheumatoid factor (RF) and since the earliest reports a role has been proposed in the diagnosis and in the prediction of clinical features and outcome. The study of RF isotypes has further attempted to improve diagnostic accuracy and identify specific subgroups of patients. The main objective of this study is to provide an analysis of the literature on the role of RF isotypes in the diagnosis and prognosis of rheumatoid arthritis (RA).
METHODS
We performed a systematic literature review and meta-analysis on the role of RF isotypes in RA (only in English, from PubMed, search terms: "rheumatoid factor isotypes", "diagnosis", "prognosis" and "rheumatoid arthritis", last search 31 July 2022, two independent assessment of quality and biases, results included in tables and in the meta-analysis).
RESULTS
Thirty-six articles were examined (7517 patients). Testing all RF isotypes with latex test or nephelometry allows for the highest sensitivity (68.6%, 95% CI 66.2% to 71.0%); nonetheless, the determination of IgA isotype provides the highest specificity (91.4%, 95% CI 90.8% to 92.0%) and the highest positive likelihood ratio (7.7, 95% CI 5.7 to 10.4). When testing IgM isotype the highest diagnostic OR (21.7, 95% CI 16.1 to 29.3) is reached. When analysing anti-citrullinated protein antibodies, RF isotype determination increases diagnostic accuracy. On the other hand, these do not provide relevant prognostic information, as results are conflicting.
CONCLUSIONS
Testing RF allows the highest sensitivity, while IgA isotype the highest specificity and positive likelihood ratio for RA diagnosis. On the other hand, determination of RF isotypes dose not allow prognostic information, as data are limited and heterogeneous.
Topics: Humans; Rheumatoid Factor; Arthritis, Rheumatoid; Immunoglobulin Isotypes; Anti-Citrullinated Protein Antibodies; Immunoglobulin A
PubMed: 37541740
DOI: 10.1136/rmdopen-2022-002817 -
Autoimmunity Reviews Oct 2023Juvenile idiopathic inflammatory myopathies (JIIM) are a group of connective tissue disorders characterized by muscle inflammation and variable systemic involvement,... (Review)
Review
OBJECTIVE
Juvenile idiopathic inflammatory myopathies (JIIM) are a group of connective tissue disorders characterized by muscle inflammation and variable systemic involvement, including interstitial lung disease (ILD). Available data on JIIM-associated ILD are very limited. We performed a systematic review of the available clinical, laboratory, and radiological features of JIIM-associated ILD.
METHODS
A systematic literature review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
A total of 90 patients were identified, of whom 77.8% had JDM, 10% amyopathic JDM, 7.8% anti-synthetase syndrome, 3.3% overlap syndrome, and 1.1% juvenile polymyositis. Anti-melanoma differentiation-associated gene 5 (MDA-5/CADM-140) was the most frequently reported myositis-specific antibody (32.2%). At diagnosis of ILD, 55.5% of patients had respiratory symptoms. Ground glass opacity was the most reported radiological feature (52.9%). Thirty-three % of patients developed rapidly progressive (RP) lung disease; 26.7% were admitted to the intensive care unit (ICU); 28.9% died; all deaths were due to ILD, with a median interval of 2 months (IQR 1.5-4.7) between the onset of respiratory symptoms and death. Patients admitted to the ICU and who died of ILD were more likely to be male, to have a rapidly progressive pattern, progression of radiological features, and a higher level of KL-6.
CONCLUSIONS
MDA-5/CADM-14 is associated with RP-ILD. ILD is a rare but severe manifestation among the spectrum of systemic involvement associated with JIIM, with a high rate of ICU admission and mortality. Early recognition and aggressive treatment are needed to prevent a severe outcome.
Topics: Humans; Male; Female; Dermatomyositis; Myositis; Polymyositis; Lung Diseases, Interstitial; Lung; Autoantibodies; Retrospective Studies
PubMed: 37611886
DOI: 10.1016/j.autrev.2023.103416 -
Journal of Clinical Immunology Oct 2023Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We...
PURPOSE
Anti-interferon gamma antibody (AIGA) is a rare cause of adult onset immunodeficiency, leading to severe disseminated opportunistic infections with varying outcomes. We aimed to summarize the disease characteristics and to explore factors associated with disease outcome.
METHODS
A systematic literature review of AIGA associated disease was conducted. Serum-positive cases with detailed clinical presentations, treatment protocols, and outcomes were included. The patients were categorized into controlled and uncontrolled groups based on their documented clinical outcome. Factors associated with disease outcome were analyzed with logistic regression models.
RESULTS
A total of 195 AIGA patients were retrospectively analyzed, with 119(61.0%) having controlled disease and 76 (39.0%) having uncontrolled disease. The median time to diagnosis and disease course were 12 months and 28 months, respectively. A total of 358 pathogens have been reported with nontubercular mycobacterium (NTM) and Talaromyces marneffei as the most common pathogens. The recurrence rate was as high as 56.0%. The effective rates of antibiotics alone, antibiotics with rituximab, and antibiotics with cyclophosphamide were 40.5%, 73.5%, and 75%, respectively. In the multivariate logistic analysis, skin involvement, NTM infection, and recurrent infections remained significantly associated with disease control, with ORs of 3.25 (95% CI 1.187 ~ 8.909, P value = 0.022), 4.74 (95% CI 1.300 ~ 17.30, P value = 0.018), and 0.22 (95% CI 0.086 ~ 0.551, P value = 0.001), respectively. The patients with disease control had significant AIGA titer reduction.
CONCLUSIONS
AIGA could cause severe opportunistic infections with unsatisfactory control, particularly in patients with recurrent infections. Efforts should be made to closely monitor the disease and regulate the immune system.
Topics: Humans; Adult; Mycobacterium Infections, Nontuberculous; Retrospective Studies; Reinfection; Autoantibodies; Interferon-gamma; Immunologic Deficiency Syndromes; Opportunistic Infections; Anti-Bacterial Agents
PubMed: 37365453
DOI: 10.1007/s10875-023-01537-0