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Nutrients Sep 2023Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from... (Review)
Review
Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.
Topics: Adult; Humans; Vitamin D; Autoimmunity; COVID-19; Immune System; Autoimmune Diseases; Vitamins; Vitamin D Deficiency
PubMed: 37686873
DOI: 10.3390/nu15173842 -
Neuroscience and Biobehavioral Reviews Mar 2018Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subtype of acute-onset obsessive-compulsive disorder (OCD)...
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subtype of acute-onset obsessive-compulsive disorder (OCD) thought to be caused by an autoimmune response to group A streptococcal infection. Based on this proposed pathophysiology, alternative treatments for acute-onset OCD have been introduced, including antibiotics and immunomodulatory interventions. However, the literature on treatment of PANDAS is diverse, and clinical consensus regarding optimal treatment strategy is lacking. We conducted a systematic review of articles in PubMed, Cochrane Library, and Scopus that addressed treatment for PANDAS and related disorders. Twelve research studies involving the following treatments met inclusion criteria: penicillin, azithromycin, intravenous immunoglobulin, plasma exchange, tonsillectomy, cognitive behavior therapy, NSAID and corticosteroids. In addition, 65 case reports in which patients received immunomodulatory treatments, antibiotics, and/or psychotropics were identified. We determined that rigorously conducted research regarding treatments for PANDAS is scarce, and published studies have a high risk of bias. Further research is needed in which promising treatment strategies for PANDAS and other variants of OCD with proposed autoimmune etiology are rigorously investigated.
Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Autoimmune Diseases; Cognitive Behavioral Therapy; Humans; Obsessive-Compulsive Disorder; Plasma Exchange; Streptococcal Infections; Tonsillectomy
PubMed: 29309797
DOI: 10.1016/j.neubiorev.2018.01.001 -
JAMA Psychiatry Jun 2018With a prevalence of 4% to 13% in the United States, autoimmune thyroiditis (AIT) is a major health problem. Besides somatic complications, patients with AIT can also... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
With a prevalence of 4% to 13% in the United States, autoimmune thyroiditis (AIT) is a major health problem. Besides somatic complications, patients with AIT can also experience psychiatric disorders. The extent of these organic psychiatric diseases in patients with AIT, however, is so far not commonly known.
OBJECTIVE
To provide meta-analytic data on the association of depression and anxiety with AIT.
DATA SOURCES
Google Scholar, the EBSCO Host databases, the Web of Knowledge, and PubMed were searched from inception through December 5, 2017. Articles identified were reviewed and reference lists were searched manually.
STUDY SELECTION
Case-control studies that reported the association between AIT and either depression or anxiety disorders or both were included.
DATA EXTRACTION AND SYNTHESIS
Data extraction was performed by multiple observers following the PRISMA guidelines. Two univariate random-effects meta-analyses were performed, and moderators were tested with Bonferroni-corrected meta-regression analysis. Heterogeneity was assessed with the I2 statistic. Sensitivity analyses tested the robustness of the results. Small study effects were assessed with funnel plots and the Egger test.
MAIN OUTCOMES AND MEASURES
The odds ratio of patients with AIT and depression compared with a healthy control group, as well as the odds ratio of patients with AIT and anxiety disorders compared with a healthy control group.
RESULTS
Nineteen studies comprising 21 independent samples were included, with a total of 36 174 participants (35 168 for depression and 34 094 for anxiety). Patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had significantly higher scores on standardized depression instruments, with an odds ratio of 3.56 (95% CI, 2.14-5.94; I2 = 92.1%). For anxiety disorders, patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had an odds ratio of 2.32 (95% CI, 1.40-3.85; I2 = 89.8%). Funnel plot asymmetry was detected for studies of depression. Study quality assessed with the Newcastle-Ottawa Scale for case-control studies (mean [SD] score: anxiety, 5.77 [1.17]; depression, 5.65 [1.14]; of a possible maximum score of 9) and proportion of females did not modulate the meta-analytic estimate, whereas mean age did.
CONCLUSIONS AND RELEVANCE
This meta-analysis establishes the association between AIT and depression and anxiety disorders. Patients with AIT exhibit an increased chance of developing symptoms of depression and anxiety or of receiving a diagnosis of depression and anxiety disorders. This finding has important implications for patients and could lead to the choice of early treatment-and not only psychotherapeutic treatment-of the organic disorder.
Topics: Anxiety Disorders; Depressive Disorder; Humans; Thyroiditis, Autoimmune
PubMed: 29800939
DOI: 10.1001/jamapsychiatry.2018.0190 -
Nutrients Jan 2018Zinc is an essential trace element for living organisms and their biological processes. Zinc plays a key role in more than 300 enzymes and it is involved in cell... (Meta-Analysis)
Meta-Analysis Review
Zinc is an essential trace element for living organisms and their biological processes. Zinc plays a key role in more than 300 enzymes and it is involved in cell communication, proliferation, differentiation and survival. Zinc plays also a role in regulating the immune system with implications in pathologies where zinc deficiency and inflammation are observed. In order to examine the experimental evidence reported in the literature regarding zinc levels in the body of patients with autoimmune disorders compared to control individuals, a systematic review and meta-analysis were performed. From 26,095 articles identified by literature search, only 179 of them were considered potentially relevant for our study and then examined. Of the 179 articles, only 62 satisfied the inclusion criteria. Particularly for Fixed Model, Zn concentration in both serum (mean effect = -1.19; confidence interval: -1.26 to -1.11) and plasma (mean effect = -3.97; confidence interval: -4.08 to -3.87) samples of autoimmune disease patients was significantly lower than in controls. The data presented in our work, although very heterogeneous in the manner of collecting and investigating samples, have proved to be extremely consistent in witnessing a deficiency of zinc in serum and plasma of patients compared to controls.
Topics: Autoimmune Diseases; Autoimmunity; Deficiency Diseases; Humans; Risk Factors; Zinc
PubMed: 29324654
DOI: 10.3390/nu10010068 -
PLoS Medicine Feb 2018There is uncertainty about the influence of diet during pregnancy and infancy on a child's immune development. We assessed whether variations in maternal or infant diet... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is uncertainty about the influence of diet during pregnancy and infancy on a child's immune development. We assessed whether variations in maternal or infant diet can influence risk of allergic or autoimmune disease.
METHODS AND FINDINGS
Two authors selected studies, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) between January 1946 and July 2013 for observational studies and until December 2017 for intervention studies that evaluated the relationship between diet during pregnancy, lactation, or the first year of life and future risk of allergic or autoimmune disease. We identified 260 original studies (964,143 participants) of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies (542,672 participants) of other maternal or infant dietary exposures, including 80 trials of maternal (n = 26), infant (n = 32), or combined (n = 22) interventions. Risk of bias was high in 125 (48%) milk feeding studies and 44 (25%) studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with nonpathogenic micro-organisms (probiotics) during late pregnancy and lactation may reduce risk of eczema (Risk Ratio [RR] 0.78; 95% CI 0.68-0.90; I2 = 61%; Absolute Risk Reduction 44 cases per 1,000; 95% CI 20-64), and 6 trials suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitisation to egg (RR 0.69, 95% CI 0.53-0.90; I2 = 15%; Absolute Risk Reduction 31 cases per 1,000; 95% CI 10-47). GRADE certainty of these findings was moderate. We found weaker support for the hypotheses that breastfeeding promotion reduces risk of eczema during infancy (1 intervention trial), that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus (28 observational studies), and that probiotics reduce risk of allergic sensitisation to cow's milk (9 intervention trials), where GRADE certainty of findings was low. We did not find that other dietary exposures-including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake-influence risk of allergic or autoimmune disease. For many dietary exposures, data were inconclusive or inconsistent, such that we were unable to exclude the possibility of important beneficial or harmful effects. In this comprehensive systematic review, we were not able to include more recent observational studies or verify data via direct contact with authors, and we did not evaluate measures of food diversity during infancy.
CONCLUSIONS
Our findings support a relationship between maternal diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitisation to food, respectively.
Topics: Autoimmune Diseases; Diet; Female; Humans; Hypersensitivity; Infant; Infant Nutritional Physiological Phenomena; Infant, Newborn; Maternal Nutritional Physiological Phenomena; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors
PubMed: 29489823
DOI: 10.1371/journal.pmed.1002507 -
EBioMedicine Apr 2023The cytokine interleukin-2 (IL-2) can stimulate both effector immune cells and regulatory T (Treg) cells. The ability of selectively engaging either of these effects has...
BACKGROUND
The cytokine interleukin-2 (IL-2) can stimulate both effector immune cells and regulatory T (Treg) cells. The ability of selectively engaging either of these effects has spurred interest in using IL-2 for immunotherapy of cancer and autoimmune diseases. Thus, numerous IL-2-based biologic agents with improved bias or delivery towards effector immune cells or Treg cells have been developed. This study systematically reviews clinical results of improved IL-2-based compounds.
METHODS
We searched the ClinicalTrials.gov database for registered trials using improved IL-2-based agents and different databases for available results of these studies.
FINDINGS
From 576 registered clinical trials we extracted 36 studies on different improved IL-2-based compounds. Adding another nine agents reported in recent literature reviews and based on our knowledge totalled in 45 compounds. A secondary search for registered clinical trials of each of these 45 compounds resulted in 141 clinical trials included in this review, with 41 trials reporting results.
INTERPRETATION
So far, none of the improved IL-2-based compounds has gained regulatory approval for the treatment of cancer or autoimmune diseases. NKTR-214 is the only compound completing phase 3 studies. The PIVOT IO-001 trial testing the combination of NKTR-214 plus Pembrolizumab compared to Pembrolizumab monotherapy in metastatic melanoma missed its primary endpoints. Also the PIVOT-09 study, combining NKTR-214 with Nivolumab compared to Sunitinib or Cabozantinib in advanced renal cell carcinoma, missed its primary endpoint. Trials in autoimmune diseases are currently in early stages, thus not allowing definite conclusions on efficacy.
FUNDING
This work was supported by public funding agencies.
Topics: Humans; Antineoplastic Agents; Interleukin-2; Carcinoma, Renal Cell; Kidney Neoplasms; Immunotherapy; Autoimmune Diseases
PubMed: 37004361
DOI: 10.1016/j.ebiom.2023.104539 -
Annals of Internal Medicine Jan 2018Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with...
BACKGROUND
Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease.
PURPOSE
To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions.
STUDY SELECTION
Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs.
DATA EXTRACTION
2 reviewers independently extracted data and assessed the quality of reporting.
DATA SYNTHESIS
123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have fewer adverse events than those not receiving treatment. Most flares and irAEs were managed with corticosteroids; 16% required other immunosuppressive therapies. Adverse events improved in more than half of patients without discontinuation of CPI therapy. Three patients died of adverse events.
LIMITATIONS
The quality and quantity of data were limited. Case reports typically describe unique manifestations and are not generalizable to the population at large. Because there were no prospective observational studies, incidence could not be determined.
CONCLUSION
Flares and irAEs in patients with autoimmune disease who are receiving CPIs can often be managed without discontinuing therapy, although some events may be severe and fatal. Prospective longitudinal studies are needed to establish incidence of adverse events and evaluate risk-benefit ratios and patient preferences in this population.
PRIMARY FUNDING SOURCE
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Topics: Antineoplastic Agents, Immunological; Autoimmune Diseases; Cell Cycle Checkpoints; Humans; Immunotherapy; Neoplasms
PubMed: 29297009
DOI: 10.7326/M17-2073 -
Frontiers in Immunology 2020Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous...
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous system and the haematopoietic system, with a large number of complications. Despite years of study, the etiology of SLE remains unclear; thus, safe and specifically targeted therapies are lacking. In the last 20 years, researchers have explored the potential of nutritional factors on SLE and have suggested complementary treatment options through diet. This study systematically reviews and evaluates the clinical and preclinical scientific evidence of diet and dietary supplementation that either alleviate or exacerbate the symptoms of SLE. For this review, a systematic literature search was conducted using PubMed, Scopus and Google Scholar databases only for articles written in the English language. Based on the currently published literature, it was observed that a low-calorie and low-protein diet with high contents of fiber, polyunsaturated fatty acids, vitamins, minerals and polyphenols contain sufficient potential macronutrients and micronutrients to regulate the activity of the overall disease by modulating the inflammation and immune functions of SLE.
Topics: Animals; Diet; Diet Therapy; Dietary Supplements; Fatty Acids, Unsaturated; Humans; Immunomodulation; Lupus Erythematosus, Systemic; Minerals; Polyphenols
PubMed: 32793202
DOI: 10.3389/fimmu.2020.01477 -
RMD Open 2019To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League Against Rheumatism treatment recommendations.
METHODS
The MEDLINE, EMBASE and Cochrane databases were searched for case-control/prospective cohort studies, randomised controlled trials (RCTs) and systematic reviews.
RESULTS
Current evidence in primary SjS patients fulfilling the 2002 criteria is based on the data from 9 RCTs, 18 prospective cohort studies and 5 case-control studies. Two Cochrane systematic literature reviews (SLRs) have reported that topical treatments for dry mouth and dry eye are safe and effective. Ocular cyclosporine A was safe and effective in two RCTs including 1039 patients with dry eye syndrome. Two Cochrane SLRs on serum tear drops and plugs showed inconsistency in possible benefits, both for symptoms and objective measures. Five RCTs reported significant improvements in oral dryness and salivary flow rates for pilocarpine and cevimeline. An RCT showed no significant placebo-differences for hydroxychloroquine 400 mg/day for the primary outcome (visual analogue scale (VAS) composite of dryness, fatigue and pain). We identified seven RCTs carried out in primary SjS patients. RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes. The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome (VAS composite), while prospective studies suggested efficacy in systemic disease.
CONCLUSION
The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid, while limited data from RCTs are available to guide systemic therapies.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Sjogren's Syndrome; Treatment Outcome
PubMed: 31749986
DOI: 10.1136/rmdopen-2019-001064 -
International Journal of Molecular... Nov 2022Autoimmune thyroid diseases (AITDs) are chronic autoimmune disorders that cause impaired immunoregulation, leading to specific immune responses against thyroid antigens.... (Meta-Analysis)
Meta-Analysis Review
Autoimmune thyroid diseases (AITDs) are chronic autoimmune disorders that cause impaired immunoregulation, leading to specific immune responses against thyroid antigens. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are the major forms of AITDs. Increasing evidence suggests a possible role of microbiota alterations in the pathogenesis and progression of AITDs. This systematic review was designed to address the following question: "Is microbiota altered in patients with AITDs?" After screening the selected studies using the inclusion and exclusion criteria, 16 studies were included in this review (in accordance with PRISMA statement guidelines). A meta-analysis revealed that patients with HT showed significantly higher values of diversity indices (except for the Simpson index) and that patients with GD showed significant tendencies toward lower values of all assessed indices compared with healthy subjects. However, the latter demonstrated a higher relative abundance of and at the phylum level and thus and at the genus level, respectively. Thyroid peroxidase antibodies showed the most significant positive and negative correlations between bacterial levels and thyroid functional parameters. In conclusion, significant alterations in the diversity and composition of the intestinal microbiota were observed in both GD and HT patients.
Topics: Humans; Hashimoto Disease; Graves Disease; Autoimmune Diseases; Microbiota
PubMed: 36362236
DOI: 10.3390/ijms232113450