Aspects Of Immune Function Research Articles

34 The influence and interaction of nutrition with the immune system in companion animal models

Abstract Understanding the impacts of nutrients in a species-specific manner has both practical and academic benefits for improving animal health. Therefore, species-specific animal models and research reagents are crucial to understanding molecular and physiological pathways. However, limitations in repeatable, descriptive models, sample size, and the ethics of companion animal research result in often needing to make inferences from human, murine, and other related immunology and nutrition research models. Recent companion animal work has focused on the impact of key nutrients in animal diets, including fat-soluble vitamins D, and E, omega-3 polyunsaturated fatty acids (PUFA), overall amino acid and energy balance over the lifespan, minerals including zinc and selenium, and feed additives such as probiotics and beta glucans. The selected research model, samples able to be collected, and available reagents for sample analysis will impact potential outcomes and inferences made from the data, including both acute to chronic impacts. From a theoretical standpoint, the balance between nutrient supplementation and impact includes understanding nutrients and responses of a model system in both deficiency and therapeutic level settings. For example, when supplementing Vitamin D, Vitamin E, or omega-3 polyunsaturated fatty acids, inclusion above currently recommended levels may optimize immune function, such as pathogen clearance, improved vaccine titer responses, or reduce inflammation. For other nutrients associated with immunomodulation such as zinc, additional chronic pharmacological supplementation may inhibit certain aspects of immune function, much like a deficiency scenario. Overstimulation of the immune system through nutrient supplementation may also impact the necessary modulation and repair roles that immune cells such as macrophages play in wound healing and anti-inflammatory responses. Continued work in nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in companion animals.

Moving toward affective immunology: Legacy and future directions

The term “affective immunology” has recently been used to denote a field focused on the interplay between affective processes (including mood states, specific emotions, and regulatory processes) and various aspects of immune function. The overarching goals of this commentary are a) to provide historical underpinnings of this field with a focus on the profound impact of the work of Janice Kiecolt-Glaser, who is further honored in this special issue, b) to review important off-shoots of her legacy work in this domain, and c) to highlight important future directions for the field. Kiecolt-Glaser's work laid much of the foundation for affective immunology, with groundbreaking research related to depression, hostility and dyadic interactions, loneliness, and other affective patterns, often in the context of holistic models, novel experimental designs, and interventions. Her former mentees (and many of their mentees) have carried on her legacy in these domains, in ways that continue to advance appreciation of how affective processes relate to immune function. There are numerous remaining questions for the field to pursue, including better understanding of the role of emotion regulation, emotional reactivity and recovery, restorative processes, affective variability, and developmental and dynamic social processes. Such work will require greater use of longitudinal and within-person approaches and/or examination of processes in daily life, as well as models that account for interactive and reciprocal processes and which integrate behavior, social context, sociocultural factors, individual differences, and other aspects of health. As more work in these domains continues, building on Kiecolt-Glaser's rich legacy, we move toward the emergence of affective immunology as an important subfield in the domain of psychoneuroimmunology, one which will offer more nuanced understanding of the role of affective processes in immune health.

Ex Vivo Immune Function and Modulatory Effects of Calcitriol in Dogs with Naturally Occurring Diabetes Mellitus.

Human patients with type 1 diabetes mellitus (T1DM) are susceptible to several long-term complications that are related to glycemic control and immune dysregulation. Immune function remains relatively unexplored in dogs with naturally occurring diabetes mellitus (NODM). Calcitriol improves various aspects of immune function in a variety of species, but its effect in diabetic dogs remains unexplored. Therefore, the objectives of this study were to (i) evaluate immune function in dogs with NODM and determine if differences exist based on the level of clinical control and (ii) assess the immunomodulatory effects of calcitriol. Twenty diabetic dogs (clinically controlled, n = ten, not controlled, n = ten) and 20 non-diabetic, healthy control dogs were included in this prospective, case-control study. Whole blood was incubated with calcitriol (10-7 M) or negative control, after which the samples were divided for phagocytosis and leukocyte cytokine response experiments. The phagocytosis of opsonized Escherichia coli (E. coli) was evaluated with flow cytometry. The samples for leukocyte cytokine response evaluations were stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or phosphate buffer solution (PBS; negative control), and tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, and IL-10 were measured in supernatant using a canine-specific multiplex bead-based assay. The leukocytes from diabetic dogs produced higher concentrations of IL-10 (p = 0.01), IL-6 (p < 0.0001), and IL-8 (p < 0.0001) than the control dogs while controlling for the intervention and stimulant. Calcitriol decreased the supernatant concentrations of TNF-α (p < 0.001) and IL-8 (p = 0.04) with concomitant increases in IL-6 (p = 0.005). Diabetic dogs had a lower percentage of leukocytes undergoing phagocytosis (p < 0.0001) but a higher number of bacteria phagocytized per cell (p = 0.001) when compared to the control dogs. Calcitriol had no effect on phagocytic capacity. Lastly, the status of clinical control in diabetic dogs did not yield differences in immune function. These results support that dogs with NODM exhibit immune dysregulation and warrant additional investigation.

A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia.

Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

Defining and targeting patterns of T cell dysfunction in inborn errors of immunity.

Inborn errors of immunity (IEIs) are a group of more than 450 monogenic disorders that impair immune development and function. A subset of IEIs blend increased susceptibility to infection, autoimmunity, and malignancy and are known collectively as primary immune regulatory disorders (PIRDs). While many aspects of immune function are altered in PIRDs, one key impact is on T-cell function. By their nature, PIRDs provide unique insights into human T-cell signaling; alterations in individual signaling molecules tune downstream signaling pathways and effector function. Quantifying T-cell dysfunction in PIRDs and the underlying causative mechanisms is critical to identifying existing therapies and potential novel therapeutic targets to treat our rare patients and gain deeper insight into the basic mechanisms of T-cell function. Though there are many types of T-cell dysfunction, here we will focus on T-cell exhaustion, a key pathophysiological state. Exhaustion has been described in both human and mouse models of disease, where the chronic presence of antigen and inflammation (e.g., chronic infection or malignancy) induces a state of altered immune profile, transcriptional and epigenetic states, as well as impaired T-cell function. Since a subset of PIRDs amplify T-cell receptor (TCR) signaling and/or inflammatory cytokine signaling cascades, it is possible that they could induce T-cell exhaustion by genetically mimicking chronic infection. Here, we review the fundamentals of T-cell exhaustion and its possible role in IEIs in which genetic mutations mimic prolonged or amplified T-cell receptor and/or cytokine signaling. Given the potential insight from the many forms of PIRDs in understanding T-cell function and the challenges in obtaining primary cells from these rare disorders, we also discuss advances in CRISPR-Cas9 genome-editing technologies and potential applications to edit healthy donor T cells that could facilitate further study of mechanisms of immune dysfunctions in PIRDs. Editing T cells to match PIRD patient genetic variants will allow investigations into the mechanisms underpinning states of dysregulated T-cell function, including T-cell exhaustion.

Effect of Exercise on Inflammation in Hemodialysis Patients: A Systematic Review.

Background: In recent years, physical exercise has been investigated for its potential as a therapeutic tool in patients with end-stage renal disease (ESRD) undergoing hemodialysis maintenance treatment (HD). It has been shown that regular practice of moderate-intensity exercise can improve certain aspects of immune function and exert anti-inflammatory effects, having been associated with low levels of pro-inflammatory cytokines and high levels of anti-inflammatory cytokines. Purpose: The aim of this review is to examine the studies carried out in this population that analyzed the effect of intradialytic exercise on the inflammatory state and evaluate which exercise modality is most effective. Methods: The search was carried out in the MEDLINE, CINAHL Web of Science and Cochrane Central Register of Controlled Trials databases from inception to June 2022. The PEDro scale was used to assess methodological quality, and the Cochrane Risk of Bias Tool and MINORS were used to evaluate the risk of bias. The quality of evidence was assessed with GRADE scale. The outcome measures were systemic inflammation biomarkers. Results: Mixed results were found in terms of improving inflammation biomarkers, such as CRP, IL-6 or TNFα, after exercise. Aerobic exercise seems to improve systemic inflammation when performed at medium intensity while resistance training produced better outcomes when performed at high intensity. However, some studies reported no differences after exercise and these results should be taken with caution. Conclusions: The low quality of the evidence suggests that aerobic and resistance exercise during HD treatment improves systemic inflammation biomarkers in patients with ESRD. In any case, interventions that increase physical activity in patients with ESRD are of vital importance as sedentary behaviors are associated with mortality. More studies are needed to affirm solid conclusions and to make intervention parameters, such as modality, dose, intensity or duration, sufficiently clear.

Diabetes Mellitus and Periodontitis: Bidirectional Relationship

Type 2 diabetes mellitus and chronic periodontitis hold a close relationship that has been the focus of many researches. Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth. Evidences stated that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Oral and periodontal health should be promoted as integral components of diabetes management.

Developmental thyroid disruption causes long-term impacts on immune cell function and transcriptional responses to pathogen in a small fish model

Current evidence suggests thyroid hormones (THs) impact development of the immune system, but few studies have explored the connection between the thyroid and immune systems, especially in fish. This is important as some environmental contaminants disrupt TH homeostasis and may thus have negative impacts on the immune system. To determine the long-term consequences of early life stage (ELS) hypothyroidism on immune function, fathead minnows were exposed to the model thyroid hormone suppressant propylthiouracil (PTU) from < 1 to 30 days post hatch. Fish were transferred to clean water and raised to adulthood (5–7 months post hatch) at which time, several aspects of immune function were evaluated. Ex vivo assessment of immune cell function revealed significant decreases (1.2-fold) in the phagocytic cell activity of PTU-treated fish relative to the controls. Fish were also injected with Yersinia ruckeri to evaluate their in vivo immune responses across a suite of endpoints (i.e., transcriptomic analysis, leukocyte counts, spleen index, hematocrit, bacterial load and pathogen resistance). The transcriptomic response to infection was significantly different between control and PTU-treated fish, though no differences in bacterial load or pathogen resistance were noted. Overall, these results suggest that early life stage TH suppression causes long-term impacts on immune function at the molecular and cellular levels suggesting a key role for TH signaling in normal immune system development. This study lays the foundation for further exploration into thyroid-immune crosstalk in fish. This is noteworthy as disruption of the thyroid system during development, which can occur in response to chemicals present in the environment, may have lasting effects on immune function in adulthood.

Correlation of Plasma Zinc with Neutralising Antioxidant Enzymes and Cellular Immune Responses in Healthy Nigerian Adults

Background: Considerable information is available on the role of micronutrient Zinc in many aspects of immune function and protection of cell membranes from oxidative damage in diseased states. To our knowledge, there are no reports relating Zinc levels with different stages neutralizing antioxidant enzymes and cellular immune processes (leucocyte migration, engulfment and intracellular killing of phagocytosis) among healthy Nigerians. &#x0D; Methodology: In 50 healthy Nigerians, cellular phagocytic mechanism [percentage leucocyte migration (%LM) and intracellular killing (%NBT)] were determined by microscopy; inflammatory cytokines [Plasma interleukin 6 (IL-6) and 8 (IL-8)] were determined using ELISA; respiratory burst indices [plasma catalase (CAT), superoxide dismutase (SOD), myeloperoxidase (MPO), hydrogen peroxide (H2O2) and nitric oxide (NO)] were determined by spectrophotometry. Zinc (Zn) was determined using AAS. Phagocytic indices, cytokines and respiratory burst indices were correlated with plasma Zn levels using Spearmans Correlation analysis at α0.05.&#x0D; Results: The result of the study shows that plasma IL-8 level was negatively correlated with Zn level while catalase was positively correlated with Zn level in healthy Nigerians.&#x0D; Conclusion: Taken together, these findings suggest that immuno-potential effect of Zn may include production of protective antioxidant neutralizing enzyme (catalase) and reduction of IL-8 inflammatory cytokine.&#x0D; Recommendation: These findings raise the possibility that Zn supplementation or Zn containing diets may be beneficial to individuals with intracellular infection or inflammatory diseases.

Nutrient modulation of viral infection-implications for COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has put focus on the importance of a healthy immune system for recovery from infection and effective response to vaccination. Several nutrients have been under attention because their nutritional statuses showed associations with the incidence or severity of COVID-19 or because they affect several aspects of immune function. Nutritional status, immune function, and viral infection are closely interrelated. Undernutrition impairs immune function, which can lead to increased susceptibility to viral infection, while viral infection itself can result in changes in nutritional status. Here, we review the roles of vitamins A, C, D, and E, and zinc, iron, and selenium in immune function and viral infection and their relevance to COVID-19.

Contribution of Th17 cells to tissue injury in hypertension.

Hypertension has been demonstrated to be a chief contributor to morbidity and mortality throughout the world. Although the cause of hypertension is multifactorial, emerging evidence, obtained in experimental studies, as well as observational studies in humans, points to the role of inflammation and immunity. Many aspects of immune function have now been implicated in hypertension and end-organ injury; this review will focus upon the recently-described role of Th17 cells in this pathophysiological response. Studies in animal models and human genetic studies point to a role in the adaptive immune system as playing a contributory role in hypertension and renal tissue damage. Th17 cells, which produce the cytokine IL17, are strongly pro-inflammatory cells, which may contribute to tissue damage if expressed in chronic disease conditions. The activity of these cells may be enhanced by physiological factors associated with hypertension such as dietary salt or Ang II. This activity may culminate in the increased sodium retaining activity and exacerbation of inflammation and renal fibrosis via multiple cellular mechanisms. Th17 cells are a distinct component of the adaptive immune system that may strongly enhance pathways leading to increased sodium reabsorption, elevated vascular tone and end-organ damage. Moreover, this pathway may lend itself towards specific targeting for treatment of kidney disease and hypertension.

Effects of diets, foods and nutrients on immunity: Implications for COVID‐19?

AbstractThe COVID‐19 pandemic has sparked an increase in claims that particular food and drink products and nutritional supplements are able to ‘boost’ immunity. The immune system is highly complex, consisting of many different cell types and processes, and nutritional adequacy is undoubtedly required to support its function. Specific roles have been established for several micronutrients including vitamins A, B6, B12, C and D, copper, folate, iron, selenium and zinc, with documented impacts on particular aspects of immune function as a result of clinical deficiencies. Increased susceptibility to infections and poorer outcomes have been commonly observed in cases of undernutrition. However, high bodyweight, diabetes and ageing are also associated with immune dysfunction. The gut microbiota is intimately linked with the immune system and there is some evidence to suggest that food components that favourably modify its composition, such as pre‐ and probiotics, may be advantageous in immune modulation. Studies also indicate some benefits of specific supplements; for example, zinc and vitamin C supplements have been shown to reduce the duration of the common cold; probiotics have been suggested to reduce the duration and severity of acute infectious diarrhoea and prevent antibiotic‐associated diarrhoea; and anti‐inflammatory effects of long‐chain omega‐3 fatty acids have also been demonstrated. However, at present there are no authorised EU health claims for any of these effects. In the light of the recent media interest in the role of diet and lifestyle on the immune system following the COVID‐19 outbreak, this article will summarise why a healthy, balanced diet is key to supporting immune function with consideration given to the latest thinking in relation to COVID‐19.

Genetic background and thermal environment differentially influence the ontogeny of immune components during early life in an ectothermic vertebrate.

An understudied aspect of vertebrate ecoimmunology has been the relative contributions of environmental factors (E), genetic background (G) and their interaction (G×E) in shaping immune development and function. Environmental temperature is known to affect many aspects of immune function and alterations in temperature regimes have been implicated in emergent disease outbreaks, making it a critical environmental factor to study in the context of immune phenotype determinants of wild animals. We assessed the relative influences of environmental temperature, genetic background and their interaction on first-year development of innate and adaptive immune defences of captive-born garter snakes Thamnophis elegans using a reciprocal transplant laboratory experiment. We used a full-factorial design with snakes from two divergent life-history ecotypes, which are known to differ in immune function in their native habitats, raised under conditions mimicking the natural thermal regime-that is, warmer and cooler-of each habitat. Genetic background (ecotype) and thermal regime influenced innate and adaptive immune parameters of snakes, but in an immune-component specific manner. We found some evidence of G×E interactions but no indication of adaptive plasticity with respect to thermal environment. At the individual level, the effects of thermal environment on resource allocation decisions varied between the fast- and the slow-paced life-history ecotypes. Under warmer conditions, which increased food consumption of individuals in both ecotypes, the former invested mostly in growth, whereas the latter invested more evenly between growth and immune development. Overall, immune parameters were highly flexible, but results suggest that other environmental factors are likely more important than temperature per se in driving the ecotype differences in immunity previously documented in the snakes under field conditions. Our results also add to the understanding of investment in immune development and growth during early postnatal life under different thermal environments. Our finding of immune-component specific patterns strongly cautions against oversimplification of the highly complex immune system in ecoimmunological studies. In conjunction, these results deepen our understanding of the degree of immunological flexibility wild animals present, information that is ever more vital in the context of rapid global environmental change.

Effects of tumor necrosis factor on viral replication and pulmonary inflammation during acute mouse adenovirus type 1 respiratory infection

CD8 T cells contribute to effective clearance of mouse adenovirus type 1 (MAV-1) and to virus-induced pulmonary inflammation. We characterized effects of a CD8 T cell effector, TNF, on MAV-1 pathogenesis. TNF inhibited MAV-1 replication in vitro. TNF deficiency or immunoneutralization had no effect on lung viral loads or viral gene expression in mice infected intranasally with MAV-1. Absence of TNF delayed virus-induced weight loss and reduced histological evidence of pulmonary inflammation, although concentrations of proinflammatory cytokines and chemokines in bronchoalveolar lavage fluid (BALF) were not significantly affected. BALF concentrations of IL-10 were greater in TNF-deficient mice compared to controls. Our data indicate that TNF is not essential for control of viral replication in vivo, but virus-induced TNF contributes to some aspects of immunopathology and disease. Redundant CD8 T cell effectors and other aspects of immune function are sufficient for antiviral and pro-inflammatory responses to acute MAV-1 respiratory infection.

Immune function during early adolescence positively predicts adult facial sexual dimorphism in both men and women

Evolutionary theories suggest that humans prefer sexual dimorphism in faces because masculinity in men and femininity in women may be an indicator of immune function during development. In particular, the immunocompetence handicap hypothesis proposes that sexual dimorphism indicates good immune function during development because the sex hormones, particularly testosterone in men, required for the development of sexually dimorphic facial features also taxes the immune system. Therefore, only healthy males can afford the high level of testosterone for the development of sexually dimorphic traits without compromising their survival. Researchers have suggested that a similar mechanism via the effects of oestrogen might also explain male preferences for female femininity. Despite the prominence of the immunocompetence handicap hypothesis, no studies have tested whether immune function during development predicts adult facial sexual dimorphism. Here, using data from a longitudinal public health dataset, the Western Australian Pregnancy Cohort (Raine) Study (Generation 2), we show that some aspects of immune function during early adolescence (14 years) positively predict sexually dimorphic 3D face shape in both men and women. Our results support a fundamental assumption that facial sexual dimorphism is an indicator of immune function during the development of facial sexual dimorphism.

Effects of BDE-47 exposure on immune-related parameters of Mytilus galloprovincialis

The persistent pollutants polybrominated diphenyl ethers (PBDEs) have been demonstrated to produce several negative effects on marine organisms. Although Mytilus galloprovincialis was extensively studied as model system, the effects of PBDEs on the innate immune system of mussels remains unclear. In this study, except for the control treatment, specimens of M. galloprovincialis were fed with microalgae treated with increasing concentrations of PBDEs (maximum level 100 ng L−1 of BDE-47 per day). BDE-47 treatment was maintained for 15 days and then the animals were fed with the same control diet, without contaminants, for 15 days. Samples of haemolymph (HL) were obtained at T0, T15 and T30 days of the experiment to evaluate different parameters related to immunity, such as neutral red retention time, and peroxidase, protease, antiprotease, lysozyme and bactericidal activities. BDE-47 exposure for 15 days affected both the stability of haemocytes and humoral parameters. In addition, the obtained results indicated that, at 30 days, after 15 days of culture without contaminant, the immune parameters were still affected, as some of them did not return to the basal levels, and others remained stimulated. Overall the results indicate that BDE-47 exposures at environmentally realistic levels may affect various aspects of immune function in M. galloprovincialis, acting as stressor that can compromise the general welfare.

Immune function as predictor of infectious complications and clinical outcome in patients undergoing solid organ transplantation (the ImmuneMo:SOT study): a prospective non-interventional observational trial

BackgroundSolid organ transplantation (SOT) is a well-established and life-saving treatment for patients with end-stage organ failure. Organ rejection and infections are among the main complications to SOT and largely determines the clinical outcome. The correct level of immunosuppression is of major importance to prevent these complications. However, it is a consistent observation that in recipients on the same immunosuppressive regimens the clinical outcome varies, and no reliable marker exists to monitor immune function.MethodsIn a prospective, observational study, we plan to enroll 630 adult patients with a planned organ transplantation at Rigshospitalet, University of Copenhagen, Denmark. Prior to and on different time points up to two years after transplantation we will perform a complete immunological profile on the recipients. This profile will consist of classical descriptive immune phenotyping (flow cytometry and circulating biomarkers) and the functional assay TruCulture®. In TruCulture® whole blood is incubated ex vivo with stimulants imitating bacterial, viral and fungal infections, where after a panel of selected cytokines is quantified. Clinical data from electronic health records will be obtained from the PERSIMUNE (Centre of Excellence for Personalized Medicine of Infections Complications in Immune Deficiency at Rigshospitalet, Copenhagen) data repository, a warehouse of data generated as part of routine care including vital signs, biochemistry, microbiology, pathology as well as medication, demographics, diagnoses, hospital contacts, surgical procedures and mortality.DiscussionThis will be the first large scale study to determine several aspects of immune function and perform a complete immunological profiling in SOT recipients. It is expected that knowledge generated will provide information to generate prediction models identifying patients at increased risk of infection and/or rejection. If the study is successful, we will subsequently use the generated prediction models to propose personalized immunosuppressive regimens to be tested in future randomized controlled trials.Trial registrationThis study has been approved by the Regional ethical committee (H-17024315), the Danish Data Protection Agency (RH-2016-47, RH-2015-04, I-Suite 03605) and the Danish National board of Health (3–3013-1060/1). The trial is retrospectively registered at clinicaltrials.gov (NCT03847285) the 20th February 2019.

Abstract 1343: SNPs in the NFKB alternative pathway genes CD40, BAFFR and LTβR in CRC

Abstract We sought to assess the role of single nucleotide polymorphisms (SNPs) in genes of the alternative NF-KB pathway, important in regulating different aspects of immune functions in colorectal cancer (CRC). The study comprised DNA samples from 418 patients with CRC and 299 age-matched healthy individuals. Genotyping was performed with real time PCR followed by high resolution melt curve analysis for the following SNPs: CD40 rs1883832 (C/T), BAFFR rs7290134 (A/G), LTβR rs10849448 (A/G). Genotypes of random samples were confirmed by sequencing. Genotype frequencies differed between CRC and healthy individuals for CD40 rs1883832 and LTβR rs10849448 (p = 0.001 and p = 0.016, respectively) but were similar for BAFFR rs7290134. The LTβR rs10849448 G allele was more frequent in CRC patients compared to healthy controls and increased risk for CRC by 61% (p = 0.024). Moreover, the G allele was found more frequently in stage D patients compared to stages A and C while the A allele was more prevalent in stage B patients (p = 0.007). Additionally, most patients with grade III tumors were G allele carriers whereas the majority of grade I tumors were AA homozygotes (p = 0.019). The CD40 rs1883832 T allele was less frequent in CRC patients and reduced risk for CRC by 71% (p = 0.027). The CD40 rs1883832 SNP proved to be a prognostic factor for PFS with the CC individuals displaying a longer PFS compared to T carriers (p = 0.045). The BAFFR rs7290134 SNP was independent of all clinical parameters evaluated. Primary site was independent of genotypes for all three SNPs. SNPs within genes of receptors of the NF-KB alternative pathway, CD40 rs1883832 and LTβR rs10849448, influence PFS and risk for CRC development. Additionally, particular genotypes correlated with stage and grade. Citation Format: Anna Antonacopoulou, Anastasia Kottorou, Angelos Koutras, Foteinos-Ioannis Dimitrakopoulos, Thomas Makatsoris, Haralabos P. Kalofonos. SNPs in the NFKB alternative pathway genes CD40, BAFFR and LTβR in CRC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1343.

Differences in Interleukin-8 Plasma Levels between Diabetic Patients and Healthy Individuals Independently on Their Periodontal Status.

Chronic periodontitis (CP) and diabetes mellitus (DM) involve several aspects of immune functions, including neutrophil activity and cytokine biology. Considering the critical function of chemokine interleukin-8 (IL-8) in the inflammatory process, the aims of this study were to determine: (i) IL-8 plasma levels; (ii) IL-8 (−251A/T, rs4073) and its receptor 2 (CXCR2, +1208C/T, rs1126579) polymorphisms, and (iii) the presence of the selected periodontal bacteria in types 1 and 2 DM patients (T1DM and T2DM) and systemically healthy controls (HC) with known periodontal status. This case–control study comprises of 153 unrelated individuals: 36/44 patients suffering from T1DM+CP/T2DM+CP and 32/41 from HC+CP/non-periodontitis HC. Both the clinical and biochemical parameters were monitored. The genotypes were determined using qPCR, IL-8 plasma levels were measured using an ELISA kit. Subgingival bacterial colonization was analyzed with a DNA microarray detection kit. The IL-8 plasma levels differed significantly between non-periodontitis HC and T1DM+CP/T2DM+CP patients (P < 0.01). Even in HC+CP, IL-8 concentrations were significantly lower than in T1DM+CP/T2DM+CP patients (P ≤ 0.05). No significant associations between the IL-8 plasma levels and the studied IL-8 and CXCR2 polymorphisms or the occurrence of selected periodontal bacteria (P > 0.05) were found. CP does not influence the circulating IL-8 levels. Patients with T1DM+CP/T2DM+CP had higher circulating IL-8 levels than HC+CP/non-periodontitis HC.

The alternative NF-κB pathway in colorectal cancer: From genetic polymorphisms through mRNA to protein levels.

e15619Background: In colorectal cancer (CRC), there is scarce information regarding the alternative NF-κB pathway which regulates different aspects of immune functions. Methods: Formalin-fixed para...