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1.
Selenium Deficiency Due to Diet, Pregnancy, Severe Illness, or COVID-19-A Preventable Trigger for Autoimmune Disease.
Schomburg, L
International journal of molecular sciences. 2021;(16)
Abstract
The trace element selenium (Se) is an essential part of the human diet; moreover, increased health risks have been observed with Se deficiency. A sufficiently high Se status is a prerequisite for adequate immune response, and preventable endemic diseases are known from areas with Se deficiency. Biomarkers of Se status decline strongly in pregnancy, severe illness, or COVID-19, reaching critically low concentrations. Notably, these conditions are associated with an increased risk for autoimmune disease (AID). Positive effects on the immune system are observed with Se supplementation in pregnancy, autoimmune thyroid disease, and recovery from severe illness. However, some studies reported null results; the database is small, and randomized trials are sparse. The current need for research on the link between AID and Se deficiency is particularly obvious for rheumatoid arthritis and type 1 diabetes mellitus. Despite these gaps in knowledge, it seems timely to realize that severe Se deficiency may trigger AID in susceptible subjects. Improved dietary choices or supplemental Se are efficient ways to avoid severe Se deficiency, thereby decreasing AID risk and improving disease course. A personalized approach is needed in clinics and during therapy, while population-wide measures should be considered for areas with habitual low Se intake. Finland has been adding Se to its food chain for more than 35 years-a wise and commendable decision, according to today's knowledge. It is unfortunate that the health risks of Se deficiency are often neglected, while possible side effects of Se supplementation are exaggerated, leading to disregard for this safe and promising preventive and adjuvant treatment options. This is especially true in the follow-up situations of pregnancy, severe illness, or COVID-19, where massive Se deficiencies have developed and are associated with AID risk, long-lasting health impairments, and slow recovery.
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2.
Epidemiology of Ocular Manifestations in Autoimmune Disease.
Glover, K, Mishra, D, Singh, TRR
Frontiers in immunology. 2021;:744396
Abstract
The global prevalence of autoimmune diseases is increasing. As a result, ocular complications, ranging from minor symptoms to sight-threatening scenarios, associated with autoimmune diseases have also risen. These ocular manifestations can result from the disease itself or treatments used to combat the primary autoimmune disease. This review provides detailed insights into the epidemiological factors affecting the increasing prevalence of ocular complications associated with several autoimmune disorders.
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3.
Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity.
Mansueto, P, Soresi, M, Candore, G, Garlisi, C, Fayer, F, Gambino, CM, La Blasca, F, Seidita, A, D'Alcamo, A, Lo Sasso, B, et al
The American journal of gastroenterology. 2021;(5):1015-1023
Abstract
INTRODUCTION Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS. METHODS Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were measured. Human leukocyte antigen haplotypes were determined, and duodenal histology performed in all patients carrying the DQ2/DQ8 haplotypes. Participants completed a questionnaire, and their medical records were reviewed to identify those with ADs. RESULTS Twenty-three patients with NCWS (25.3%) presented with ADs; autoimmune thyroiditis (16 patients, 17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD (P = 0.002) and in patients with IBS (P = 0.05). In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both). The frequency of extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS (21.9%) than in HBD (0%) and patients with IBS (3.6%) (P = 0.0001 and P = 0.004, respectively). Among the patients with NCWS, 9.9% tested positive for antithyroglobulin, 16.5% for antithyroid peroxidase, and 14.3% for antiparietal cell antibodies; frequencies were not statistically different from controls. The presence of ADs was related to older age at NCWS diagnosis, female sex, duodenal lymphocytosis, and eosinophil infiltration. DISCUSSION One in 4 patients with NCWS suffered from AD, and serum antinuclear antibodies were positive in a very high percentage of cases. These data led us to consider NCWS to be associated to ADs.
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4.
Nutri-epigenetics: the effect of maternal diet and early nutrition on the pathogenesis of autoimmune diseases.
Bangarusamy, DK, Lakshmanan, AP, Al-Zaidan, S, Alabduljabbar, S, Terranegra, A
Minerva pediatrics. 2021;(2):98-110
Abstract
Autoimmune diseases comprise a wide group of diseases involving a self-response of the immune system against the host. The etiopathogenesis is very complex involving disease-specific factors but also environmental factors, among which the diet. Maternal diet during pregnancy as well as early nutrition recently attracted the interest of the scientists as contributing to the immune programming. In this paper, we reviewed the most recent literature on the effect of maternal diet and early nutrition in modulating the immune system in a selected subset of autoimmune diseases: type 1 diabetes, celiac disease, inflammatory bowel disease, juvenile idiopathic arthritis and rheumatoid arthritis. Particularly, we focused our narrative on the role of maternal and perinatal nutrition in the epigenetic mechanisms underlying the auto-immune response. Maternal diet during pregnancy as well as breastfeeding and early nutrition play a big role in many epigenetic mechanisms. Most of the nutrients consumed by the mother and the infant are known exerting epigenetic functions, such as folate, methionine, zinc, vitamins B12 and D, fibers, casein and gliadin, and they were linked to gene expression changes in the immune pathways. Despite the common role of maternal diet, breastfeeding and early nutrition in almost all the autoimmune diseases, each disease seems to have specific diet-driver epigenetic mechanisms that require further investigations. The research in this field is opening new routes to establishing a precision nutrition approach to the auto-immune diseases.
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5.
Effects of physical activity on vascular function in autoimmune rheumatic diseases: a systematic review and meta-analysis.
Peçanha, T, Bannell, DJ, Sieczkowska, SM, Goodson, N, Roschel, H, Sprung, VS, Low, DA
Rheumatology (Oxford, England). 2021;(7):3107-3120
Abstract
OBJECTIVES To summarize existing evidence and quantify the effects of physical activity on vascular function and structure in autoimmune rheumatic diseases (ARDs). METHODS Databases were searched (through March 2020) for clinical trials evaluating the effects of physical activity interventions on markers of micro- and macrovascular function and macrovascular structure in ARDs. Studies were combined using random effects meta-analysis, which was conducted using Hedges' g. Meta-analyses were performed on each of the following outcomes: microvascular function [i.e. skin blood flow or vascular conductance responses to acetylcholine (ACh) or sodium nitropusside (SNP) administration]; macrovascular function [i.e. brachial flow-mediated dilation (FMD%) or brachial responses to glyceryl trinitrate (GTN%); and macrovascular structure [i.e. aortic pulse wave velocity (PWV)]. RESULTS Ten studies (11 trials) with a total of 355 participants were included in this review. Physical activity promoted significant improvements in microvascular [skin blood flow responses to ACh, g = 0.92 (95% CI 0.42, 1.42)] and macrovascular function [FMD%, g = 0.94 (95% CI 0.56, 1.02); GTN%, g = 0.53 (95% CI 0.09, 0.98)]. Conversely, there was no evidence for beneficial effects of physical activity on macrovascular structure [PWV, g = -0.41 (95% CI -1.13, 0.32)]. CONCLUSIONS Overall, the available clinical trials demonstrated a beneficial effect of physical activity on markers of micro- and macrovascular function but not on macrovascular structure in patients with ARDs. The broad beneficial impact of physical activity across the vasculature identified in this review support its role as an effective non-pharmacological management strategy for patients with ARDs.
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6.
Effect of synbiotics and probiotics supplementation on autoimmune diseases: A systematic review and meta-analysis of clinical trials.
Askari, G, Ghavami, A, Shahdadian, F, Moravejolahkami, AR
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3221-3234
Abstract
BACKGROUND & AIMS Today synbiotics are considered as immunomodulatory agents. The current systematic review and meta-analysis investigated the effect of synbiotics and probiotics on inflammatory and oxidative stress markers in autoimmune disease. MATERIALS & METHODS The English literature search was performed using PubMed, Scopus, Web of Science, and the Central Cochrane Library through March 2020. Random effects models and generic inverse variance methods were used to synthesize quantitative data by STATA14. RESULTS From a total of 623 entries identified via searches, ten RCTs (n = 440; 216 as intervention, 224 as controls) were included. An additional eleven studies with same intervention and different markers were also explained systematically. The pooled effect size showed that Interleukin (IL)-6 (WMD = -7.79 pg/ml; 95% CI = -13.81, -1.77, P = 0.011), Tumor Necrosis Factor (TNF)-α (WMD = -1.05 pg/ml; 95% CI = -2.01, -0.10, P = 0.030), high sensitivity C-Reactive Protein (hs-CRP) (SMD = -0.58; 95% CI = -0.79, -0.37, P < 0.001), Malondialdehyde (MDA) (SMD = -0.36; 95% CI = -0.68, -0.04; P = 0.026), Homeostasis Model of Assessment-estimated Insulin Resistance (HOMA-IR) (WMD = -0.71; 95% CI = -1.05, -0.37, P < 0.001), and beta cell function (HOMA-β) (WMD = -15.18; 95% CI = -22.08, -8.28, P < 0.001) changed following probiotics (or synbiotics) supplementation. Also supplementation with doses more than 2 billion CFU could reduce IL-10 concentrations (WMD = -1.84; 95% CI = -2.23, 1.87; P < 0.001). Glutathione (GSH) and Total Antioxidant Capacity (TAC) levels did not influence by synbiotics and probiotics; insignificancy was remained after subgrouping for participants' age, study duration, and disease duration. CONCLUSION Our findings revealed that synbiotics and probiotics supplementation has significant effect on some inflammatory and oxidative stress markers; although, the number of trials was too small to powerful conclusion and further investigations may be needed.
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7.
Vitamin D in autoimmune bullous disease.
Tukaj, S
Acta biochimica Polonica. 2020;(1):1-5
Abstract
Numerous epidemiological studies have suggested a link between vitamin D deficiency and the development of various autoimmune diseases, including diabetes mellitus type 1, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis or systemic lupus erythematosus. More recently, such a link has been also proposed for autoimmune bullous diseases (AIBD). This is a relatively rare and potentially life-threatening, organ-specific group of inflammatory skin diseases characterized by the presence of tissue-bound and circulating autoantibodies against various molecules present in desmosomes (in pemphigus diseases) or hemidesmosomes (in pemphigoid diseases). In addition to the well-known role of vitamin D in calcium and phosphate homeostasis, the hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (calcitriol), exerts potent effects on cellular differentiation and regulation of immune responses via binding to the vitamin D receptor present in most cells of the immune system. Since cells of both, the innate and adaptive immune systems, are known to be relevant in AIBD, the role of vitamin D analogues in the treatment of patients with these disorders deserves much attention. This mini-review summarizes recent epidemiological and experimental studies on vitamin D involvement in the autoimmune bullous diseases.
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8.
How does methotrexate work?
Alqarni, AM, Zeidler, MP
Biochemical Society transactions. 2020;(2):559-567
Abstract
Developed over 70 years ago as an anti-folate chemotherapy agent, methotrexate (MTX) is a WHO 'essential medicine' that is now widely employed as a first-line treatment in auto-immune, inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and Crone's disease. When used for these diseases patients typically take a once weekly low-dose of MTX - a therapy which provides effective inflammatory control to tens of millions of people worldwide. While undoubtedly effective, our understanding of the anti-inflammatory mechanism-of-action of low-dose MTX is incomplete. In particular, the long-held dogma that this disease-modifying anti-rheumatic drug (DMARD) acts via the folate pathway does not appear to hold up to scrutiny. Recently, MTX has been identified as an inhibitor of JAK/STAT pathway activity, a suggestion supported by many independent threads of evidence. Intriguingly, the JAK/STAT pathway is central to both the inflammatory and immune systems and is a pathway already targeted by other RA treatments. We suggest that the DMARD activity of MTX is likely to be largely mediated by its inhibition of JAK/STAT pathway signalling while many of its side effects are likely associated with the folate pathway. This insight into the mechanism-of-action of MTX opens the possibility for repurposing this low cost, safe and effective drug for the treatment of other JAK/STAT pathway-associated diseases.
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9.
Transfer of monoclonal antibodies into breastmilk in neurologic and non-neurologic diseases.
LaHue, SC, Anderson, A, Krysko, KM, Rutatangwa, A, Dorsey, MJ, Hale, T, Mahadevan, U, Rogers, EE, Rosenstein, MG, Bove, R
Neurology(R) neuroimmunology & neuroinflammation. 2020;(4)
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Abstract
OBJECTIVE To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. METHODS We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women. RESULTS Drug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (<10% is generally considered safe), was evaluated for certolizumab (<1%), rituximab (<1%), and natalizumab (maximum of 5.3%; cumulative effects of monthly dosing are anticipated). Importantly, a total of 368 infants were followed for ≥6 months after exposure to breastmilk of mothers treated with mAbs; none experienced reported developmental delay or serious infections. CONCLUSIONS The current data are reassuring for low mAb drug transfer to breastmilk, but further studies are needed, including of longer-term effects on infant immunity and childhood development.
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10.
Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.
Koźmiński, P, Halik, PK, Chesori, R, Gniazdowska, E
International journal of molecular sciences. 2020;(10)
Abstract
Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discussed.