Risk of autoimmune diseases in patients with RASopathies: systematic study of humoral and cellular immunity

Abstract Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of patients affected by RASopathies.Study Design. A cohort of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at “ScuolaMedicaSalernitana”, Salerno. An age- and sex-matched control group was also enrolled. Autoimmune disorders were investigated in the study cohort according to international consensus criteria. Immune framework was also evaluated by immunoglobulin levels,CD3, CD4, CD8, CD19, CD56 lymphocyte subpopulations, autoantibodies levels and panel of inflammatory molecules, in both patients and controls.Results. Frequent upper respiratory tract infections were recorded in 2 patients; pneumonia, psoriasis and alopecia in single patients. Low IgA levels were detected in 8/44 patients (18.18%),low CD8 T cells in 13/35 patients (37.14%).Anti-tg and anti-TPO antibodies were detected in 3/24 patients (12.5%), anti r-TSH in 2 cases (8.33%), all in euthyroidism. Serum IgA and CD8 levels were significantly lower in patients than in controls (p 0,00685; p 0,000656 respectively). All tested patients showed increased inflammatory molecules compared to controls. These findings may anticipate the detection of overt autoimmune disease.Conclusions. Patients affected by RASopathiesare at risk to develop autoimmune disorders. Routine screening for autoimmunity is recommendedin patients with RASopathy.

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Risk of autoimmune diseases in patients with RASopathies: systematic study of humoral and cellular immunity

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-021-02050-6 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

M. A. Siano ◽

V. Marchetti ◽

S. Pagano ◽

F. Di Candia ◽

M. Alessio ◽

...

Keyword(s):

Immune System ◽

Autoimmune Disorders ◽

Control Group ◽

Upper Respiratory Tract ◽

International Consensus ◽

Humoral And Cellular Immunity ◽

Magna Graecia ◽

Immune System Dysfunction ◽

Tract Infections ◽

Inflammatory Molecules

Abstract Background Abnormalities of the immune system are rarely reported in patients affected by RASopathies. Aim of the current study was to investigate the prevalence of immune system dysfunction in a cohort of patients affected by RASopathies. Study design A group of 69 patients was enrolled: 60 at the Federico II University, Naples, 7 at University Magna Graecia of Catanzaro, 2 at “Scuola Medica Salernitana”, Salerno. An age- and sex-matched control group was also enrolled. Autoimmune disorders were investigated according to international consensus criteria. Immune framework was also evaluated by immunoglobulin levels, CD3, CD4, CD8, CD19, CD56 lymphocyte subpopulations, autoantibodies levels and panel of inflammatory molecules, in both patients and controls. Results Frequent upper respiratory tract infections were recorded in 2 patients; pneumonia, psoriasis and alopecia in single patients. Low IgA levels were detected in 8/44 patients (18.18%), low CD8 T cells in 13/35 patients (37.14%). Anti-tg and anti-TPO antibodies were detected in 3/24 patients (12.5%), anti r-TSH in 2 cases (8.33%), all in euthyroidism. Serum IgA and CD8 levels were significantly lower in patients than in controls (p 0.00685; p 0.000656 respectively). All tested patients showed increased inflammatory molecules compared to controls. These findings may anticipate the detection of overt autoimmune disease. Conclusions Patients affected by RASopathies are at risk to develop autoimmune disorders. Routine screening for autoimmunity is recommended in patients with RASopathy.

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The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid

Viruses ◽

10.3390/v13071287 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1287

Author(s):

T. Walter ◽

Jennifer Iudicello ◽

Debra Cookson ◽

Donald Franklin ◽

Bin Tang ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Immune System ◽

Public Health Problem ◽

Control Group ◽

Csf Biomarkers ◽

Immune System Dysfunction ◽

Immune Biomarkers ◽

Plasma Factor ◽

History Of ◽

Hiv 1

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = −0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.

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A role of oropharyngeal microbiota in developing acute and chronic diseases of the upper respiratory tract

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-aro-809 ◽

2020 ◽

Vol 10 (2) ◽

pp. 359-367

Author(s):

I. I. Ababii ◽

L. A. Danilov ◽

M. K. Maniuc ◽

P. I. Ababii ◽

S. S. Ghinda ◽

...

Keyword(s):

Respiratory Tract ◽

Respiratory Tract Infections ◽

Chronic Tonsillitis ◽

Upper Respiratory Tract Infections ◽

Control Group ◽

Healthy Children ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Tract Infections

Currently, a rise in incidence of polyethological inflammation of the upper respiratory tract mucosa paralleled by altered resident and transient microbiota displaying in many cases increased antibiotic resistance has been noted. Opportunistic microbes play a major role in developing inflammatory process in Pirogov–Waldeyer’s ring. An inflammatory process occurring in the tonsillar lymphatic tissue results in host systemic complications. Fighting against acute and chronic infections of the upper respiratory tract holds the main task in pediatric otorhinolaryngology, as they can consequently elicit the cardiovascular, genitourinary and musculoskeletal complications. The results of studies examining this issue remain very contradictory, which accounted for a need to conduct our study on the territory of Moldova featured with mixed climatic conditions. Here, we wanted to study a role of microbial factor in etiopathogenesis of chronic tonsillitis in children. Bacteriological microbiota data for superficial palatine tonsils were obtained form 608 children subdivided into 5 groups: group I — 333 children with compensated chronic tonsillitis; group II — 87 children with decompensated chronic tonsillitis; group III — 91 children with acute upper respiratory tract infections (comparison group); group IV — 48 children with acute upper respiratory tract infections treated with antibiotic therapy; group V — 49 apparently healthy children (control group). It was found that β-hemolytic streptococcus exerting high sensitivity to virtually all antibiotics groups was detected in 17.4% of children with acute tonsilar inflammatory processes and decompensated defense in the lymphatic pharyngeal ring compared to 3.5% in control group. Streptococcus pneumoniae was isolated in all study groups ranging within 4.8–21.7%, including 14% in apparently healthy children characterized by reduced antibiotics sensitivity. The data obtained suggest that sickly children with acute and chronic upper respiratory tract infections constitute a risk group for developing somatic diseases. The high incidence of Streptococcus pneumoniae indicates a need for performing immunoprophylaxis, use of therapeutic vaccination as a up-to-date, combined approach in treatment of such pediatric cohort.

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The influence of a dietary advice on recurrent upper respiratory tract infections in children: a randomized controlled trial.

Proceedings of The Nutrition Society ◽

10.1017/s0029665120002554 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Ellen van der Gaag ◽

Ruben Brandsema ◽

Job van der Palen ◽

Thalia Hummel

Keyword(s):

Supportive Care ◽

Respiratory Tract Infections ◽

Controlled Trial ◽

Intervention Group ◽

Dietary Advice ◽

Control Group ◽

Upper Respiratory Tract ◽

Randomized Controlled ◽

Upper Respiratory ◽

Tract Infections

AbstractIntroductionSince there is no treatment for children suffering from upper respiratory tract infections (URTI) without immunological disorders, we searched for a possible tool to improve the health of these children.We evaluated whether a dietary advice including standard supportive care, can decrease the number and duration of URTI compared to standard supportive care in children aged 1–4 years with recurrent URTI.Material and MethodsDesign: A multicenter randomized controlled trial, with an intervention group receiving the dietary advice plus standard supportive care and a control group receiving standard supportive care alone.Setting: 3 Outpatient clinics in The Netherlands (urban and rural).Patients: 118 Children aged 1–4 years with recurrent URTIs.Intervention: A dietary advice consisting of five times per week green vegetables, 3 times per week beef, 300 mL whole milk per day, whole dairy butter on bread every day. Portion sizes are age appropriate. The intervention lasted for 6 months.ResultsChildren in the intervention group had 4.8 (1.6–9.5) days per month with symptoms of an URTI in the last three months of the study, compared to 7.7 (4.0–12.3) in the control group (p = 0.03). The total number of URTIs during the study period of 6 months was 5,7 (± 0,55) versus 6.8 (± 0,49) respectively (p = 0.068). Total use of antibiotics was markedly reduced in the intervention group (p = 0.034), as well as the visits to the general practitioner (p = 0.031), therefore possibly reducing healthcare costs.No adverse effects were observed in the lipid profiles, nor in growth parameters (weight, height, BMI).Discussion and conclusionsThis study shows a reduced number of days with symptoms of an URTI following a dietary advice consisting of green vegetables, beef and whole diary products. It did not significantly lower the number of infections. No adverse effects were observed.RegistrationThis trial is registered in the Dutch Trial Register, NTR4898, www.trialregister.nl.

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Lactobacillus rhamnosus GG can protect malnourished children

Beneficial Microbes ◽

10.3920/bm2018.0071 ◽

2019 ◽

Vol 10 (3) ◽

pp. 237-244 ◽

Cited By ~ 4

Author(s):

S.S. Kara ◽

B. Volkan ◽

I. Erten

Keyword(s):

Nutritional Status ◽

Lactobacillus Rhamnosus ◽

Control Group ◽

Study Group ◽

Upper Respiratory Tract ◽

Lactobacillus Rhamnosus Gg ◽

Malnourished Children ◽

Organ Systems ◽

Upper Respiratory ◽

Tract Infections

Malnutrition affects virtually all organ systems, and malnourished children are more prone to infections. These children have dysbiosis, but probiotics can restore the disrupted gut microbiome. We investigated the protective effects of Lactobacillus rhamnosus GG in malnourished children in terms of incidence of infection, and anthropometric and metabolic parameters. 50 intervention and 50 control patients, aged 6 months to 5 years, with body weight and height below -2 SD, were randomly and prospectively recruited. The controls received a calorie and protein-appropriate diet for 3 months, while the study group additionally received approximately 109 L. rhamnosus GG for 3 months. Infection episodes and nutritional status were compared between the groups. 38 intervention, 33 control patients completed the study and the two groups were similar at baseline. The study group had fewer upper respiratory tract infections and gastroenteritis episodes at each month and at the end of the study. Children in the study group experienced fewer total upper respiratory infections and urinary tract infections. Hospitalisation was more frequent in the control group during the third month and at the end of the study. Total infection numbers were higher in the control group at each month and at the end of the study (P<0.001 for each). Increments in body mass index (BMI) and BMI Z-scores were more pronounced in the study group (P=0.008 and P=0.02, respectively). Daily prophylactic use of L. rhamnosus GG at 109 bacteria in malnourished children prevents most infections and improves nutritional status when used together with appropriate diet.

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Probiotics Effect on the Immune System

10.20944/preprints202006.0248.v1 ◽

2020 ◽

Author(s):

Jonathan Cho Kin Ng

Keyword(s):

Immune System ◽

Respiratory Tract Infections ◽

Average Duration ◽

Small Sample Size ◽

Meta Analysis ◽

Small Sample ◽

Upper Respiratory Tract Infections ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Tract Infections

Background: Probiotics can provide health benefits to an individual by regulation of the immune system. Many clinical trials have found that probiotics can prevent upper respiratory tracts infections. Aim: To perform a systematic review and meta-analysis of available trials to investigate the effectiveness of probiotics in the prevention of upper respiratory tract infections in individuals of all ages. Conclusion: Probiotics were found to be better in reducing the number of participants who experienced acute URTI, the average duration per episode of acute URTI, use of antibiotics in URTI related cases and absence due to URTI. Side effects were found to be minor, making probiotics a good candidate for clinical use. This shows that probiotics are effective in preventing acute URTIs. However, due to limited studies and small sample size, the results are subjected to bias and should be interpreted with care.

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Whole Cell Euglena Gracilis Supplementation Reduces Upper Respiratory Tract Infection Symptoms in Healthy Adults (P19-009-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz049.p19-009-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Janaki Iyer ◽

Paul Falcone ◽

Kelli Herrlinger ◽

Joanne Lasrado ◽

Emily Pankow Fritz ◽

...

Keyword(s):

Immune System ◽

Respiratory Tract ◽

Euglena Gracilis ◽

Illness Severity ◽

Healthy Adults ◽

Upper Respiratory Tract ◽

Whole Cell ◽

Increased Risk ◽

Upper Respiratory ◽

Tract Infections

Abstract Objectives Upper respiratory tract infections (URTI) cause cold and flu-like symptoms, with roughly 70% of the general population experiencing at least one episode annually. The resultant lost productivity has a drastic impact with an estimated 40 M work or school days missed each year, translating to over $40B USD in lost potential. Certain populations, such as athletes and stressed workers are at an increased risk of URTIs. While diet, sleep, low stress and exercise are all important for a healthy functioning immune system, supplementation with natural ingredients could provide additional support. Euglena gracilis is a nutrient-rich natural microalgae (commonly consumed in Japan), containing immunomodulating beta 1,3-glucans, protein, some essential vitamins, and minerals. This double-blind, placebo-controlled, parallel study aimed at investigating the immunomodulating effects of a patented whole cell algae fermentate (WCF) in healthy active adults. Methods Thirty-four, healthy, active (1.5–3 hours/day of an aerobic sport, 5–6 days/week) participants were randomized to either WCF or placebo for 90 days. URTI symptoms were assessed Day (D) 1 to 90 using the Wisconsin Upper Respiratory Symptom Survey. Data are shown for the a priori defined per protocol population (n = 27). Results Participants supplemented with WCF reported a lower number of URTI symptoms from D1 to 30 (P = 0.042) and from D1 to 90 (P = 0.029), lower mean number of sick days between D1 and 30 (P = 0.047) and D1 and 90 (P = 0.041), lower mean number of URTI episodes per person (P = 0.032), and lower mean number of days with at least 1 reported URTI symptom per person (P = 0.019) between D1 and 90 compared to taking placebo. Evaluation of global illness severity found that the mean total AUC for daily symptoms was significantly lower in the WCF group compared to placebo at D1 to D30 (P = 0.043) and D1 to D90 (P = 0.049). Conclusions Supplementation with WCF positively influences the immune system by reducing URTI incidence, duration, and severity in healthy adults. It is noteworthy that in the absence of the intervention, active young adults reported more URTI episodes, sick days, and global illness severity, respectively. These data suggest the ability of WCF supplementation to strengthen the immune response as evidenced by reduced cold and flu symptoms. Funding Sources Kemin Foods L.C.

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Upper Respiratory Tract Infections in Sport and the Immune System Response. A Review

Biology ◽

10.3390/biology10050362 ◽

2021 ◽

Vol 10 (5) ◽

pp. 362

Author(s):

Antonio Cicchella ◽

Claudio Stefanelli ◽

Marika Massaro

Keyword(s):

Immune System ◽

Respiratory Tract ◽

Respiratory Tract Infections ◽

Upper Respiratory Tract Infections ◽

System Response ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Immune System Response ◽

Tract Infections ◽

Heavy Training

Immunity is the consequence of a complex interaction between organs and the environment. It is mediated the interaction of several genes, receptors, molecules, hormones, cytokines, antibodies, antigens, and inflammatory mediators which in turn relate and influence the psychological health. The immune system response of heavily trained athletes resembles an even more complex conditions being theorized to follow a J or S shape dynamics at times. High training loads modify the immune response elevating the biological markers of immunity and the body susceptibility to infections. Heavy training and/or training in a cold environment increase the athletes’ risk to develop Upper Respiratory Tract Infections (URTIs). Therefore, athletes, who are considered healthier than the normal population, are in fact more prone to infections of the respiratory tract, due to lowering of the immune system in the time frames subsequent heavy training sessions. In this revision we will review the behavioral intervention, including nutritional approaches, useful to minimize the “open window” effect on infection and how to cope with stressors and boost the immune system in athletes.

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ACTIVITY OF FREE RADICAL PROCESSES IN MIXED SALIVA OF PATIENTS WITH RECURRENT UPPER RESPIRATORY TRACT INFECTIONS

Clinical Practice ◽

10.17816/clinpract65014 ◽

2021 ◽

Author(s):

Tatiana S. Gomel State Medical University, Gomel ◽

Irina A. Novikova

Keyword(s):

Respiratory Tract ◽

Respiratory Tract Infections ◽

Upper Respiratory Tract Infections ◽

Antioxidant Systems ◽

Control Group ◽

Upper Respiratory Tract ◽

Diene Conjugates ◽

Upper Respiratory ◽

Tract Infections ◽

Mixed Saliva

The study conducted a comprehensive assessment of the state of the pro-/antioxidant mixed saliva system of 64 healthy individuals and 85 patients with recurrent upper respiratory tract infections RIURT. At the same time, the determination of the parameters of pro-/antioxidant systems was carried out using two methods (photometric: the content of lipid peroxidation products and the level of ceruloplasmin and luminal-dependent chemiluminescence (LDHL) was determined, which allows assessing the complex interaction of two systems - prooxidants and antioxidants). Studies have demonstrated that most patients with RIURT during remission on individual components of prooxidants (diene conjugates, ketodienes, Schiff bases;), as well as saliva antioxidant (ADS: ceruloplasmin) levels were elevated compared to controls. At the same time, the LDHL saliva parameters did not go beyond the reference interval, although they were changed relative to the median of the control group. This allows us to consider the observed fluctuations as a balance in the system of pro- and antioxidants.

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Viral Infections, the Microbiome, and Probiotics

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2020.596166 ◽

2021 ◽

Vol 10 ◽

Author(s):

Ashton Harper ◽

Vineetha Vijayakumar ◽

Arthur C. Ouwehand ◽

Jessica ter Haar ◽

David Obis ◽

...

Keyword(s):

Immune System ◽

Viral Infections ◽

Evidence Base ◽

Current Evidence ◽

Host Immune System ◽

Upper Respiratory Tract ◽

Viral Immunity ◽

Immunological Mechanisms ◽

Current Evidence Base ◽

Tract Infections

Viral infections continue to cause considerable morbidity and mortality around the world. Recent rises in these infections are likely due to complex and multifactorial external drivers, including climate change, the increased mobility of people and goods and rapid demographic change to name but a few. In parallel with these external factors, we are gaining a better understanding of the internal factors associated with viral immunity. Increasingly the gastrointestinal (GI) microbiome has been shown to be a significant player in the host immune system, acting as a key regulator of immunity and host defense mechanisms. An increasing body of evidence indicates that disruption of the homeostasis between the GI microbiome and the host immune system can adversely impact viral immunity. This review aims to shed light on our understanding of how host-microbiota interactions shape the immune system, including early life factors, antibiotic exposure, immunosenescence, diet and inflammatory diseases. We also discuss the evidence base for how host commensal organisms and microbiome therapeutics can impact the prevention and/or treatment of viral infections, such as viral gastroenteritis, viral hepatitis, human immunodeficiency virus (HIV), human papilloma virus (HPV), viral upper respiratory tract infections (URTI), influenza and SARS CoV-2. The interplay between the gastrointestinal microbiome, invasive viruses and host physiology is complex and yet to be fully characterized, but increasingly the evidence shows that the microbiome can have an impact on viral disease outcomes. While the current evidence base is informative, further well designed human clinical trials will be needed to fully understand the array of immunological mechanisms underlying this intricate relationship.

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