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Fulltext Sexual Dimorphic Responses in Lymphocytes of Healthy Individuals after Carica papaya Consumption

Jumat NR, Chong MY, Seman Z, Jamaluddin R, Wong NK, Abdullah M

Front Immunol, 2017;8:680.
PMID: 28649252 DOI: 10.3389/fimmu.2017.00680

Sexual dimorphism in immune response is widely recognized, but few human studies have observed this distinction. Food with endo-immunomodulatory potential may reveal novel sex-biased in vivo interactions. Immunomodulatory effects of Carica papaya were compared between healthy male and female individuals. Volunteers were given fixed meals supplemented with papaya for 2 days. Changes in blood immune profiles and hormone levels were determined. In females, total natural killer (NK) cell percentages decreased (12.7 ± 4.4 vs 14.6 ± 5.8%, p = 0.018, n = 18) while B cells increased (15.2 ± 5.5 vs 14.5 ± 5.0, p = 0.037, n = 18) after papaya consumption. Increased 17β-estradiol (511.1 ± 579.7 vs 282.7 ± 165.0 pmol/l, p = 0.036, n = 9) observed in females may be crucial to this change. Differentiation markers (CD45RA, CD69, CD25) analyzed on lymphocytes showed naïve (CD45RA(+)) non-CD4(+) lymphocytes were reduced in females (40.7 ± 8.1 vs 46.8 ± 5.4%, p = 0.012, n = 8) but not males. A general suppressive effect of papaya on CD69(+) cells, and higher percentage of CD69(+) populations in females and non-CD4 lymphocytes, may be relevant. CD107a(+) NK cells were significantly increased in males (16.8 ± 7.0 vs 14.7 ± 4.8, p = 0.038, n = 9) but not females. Effect in females may be disrupted by the action of progesterone, which was significantly correlated with this population (R = 0.771, p = 0.025, n = 8) after papaya consumption. In males, total T helper cells were increased (33.4 ± 6.4 vs 32.4 ± 6.1%, p = 0.040, n = 15). Strong significant negative correlation between testosterone and CD25(+)CD4(+) lymphocytes, may play a role in the lower total CD4(+) T cells reported in males. Thus, dissimilar immune profiles were elicited in the sexes after papaya consumption and may have sex hormone influence.
Fulltext Cancer-Derived Exosomes as Effectors of Key Inflammation-Related Players

Othman N, Jamal R, Abu N

Front Immunol, 2019;10:2103.
PMID: 31555295 DOI: 10.3389/fimmu.2019.02103

Exosomes, a category of small lipid bilayer extracellular vesicles that are naturally secreted by many cells (both healthy and diseased), carry cargo made up of proteins, lipids, DNAs, and RNAs; all of which are functional when transferred to their recipient cells. Numerous studies have demonstrated the powerful role that exosomes play in the mediation of cell-to-cell communication to induce a pro-tumoral environment to encourage tumor progression and survival. Recently, considerable interest has developed in regard to the role that exosomes play in immunity; with studies demonstrating the ability of exosomes to either metabolically alter immune players such as dendritic cells, T cells, macrophages, and natural killer cells. In this review, we summarize the recent literature on the function of exosomes in regulating a key process that has long been associated with the progression of cancer-inflammation and immunity.
Fulltext Overview of anti-viral effects of probiotics via immune cells in pre-, mid- and post-SARS-CoV2 era

Kanauchi O, Low ZX, Jounai K, Tsuji R, AbuBakar S

Front Immunol, 2023;14:1280680.
PMID: 38116008 DOI: 10.3389/fimmu.2023.1280680

The COVID-19 outbreak has caused significant global changes and increased public awareness of SARS-CoV-2. Substantial progress in developing vaccines, enhancing sanitation practices, and implementing various measures to combat the virus, including the utilization of probiotics has been made. This comprehensive review examined the medical impact of clinically proven probiotics on infectious diseases, considering three crucial time periods: before (pre-), during (mid-), and after (post-) COVID-19 pandemic era. This review also showed a perspective on the use of probiotics to stimulate the innate immune system and prevent infectious diseases. In pre-COVID-19 era, several probiotic strains were found to be clinically effective in addressing gastrointestinal infectious diseases, the common cold and flu. However, the mechanism by which probiotics exerted their antiviral effects remained relatively unclear during that period. Nevertheless, probiotics, Lactococcus lactis strain Plasma (LC-Plasma), and others have gained attention for their unique ability to modulate the immune system and demonstrate antiviral properties. While some probiotics have shown promise in alleviating gastrointestinal symptoms linked to COVID-19, their direct effectiveness in treating or preventing COVID-19 progression has not yet been conclusively established. As we transition into the post-COVID-19 era, the relationship between COVID-19 and plasmacytoid dendritic cells (pDCs), a vital component of the innate immune system, has been gradually elucidated. These findings are now being applied in developing novel vaccines and treatments involving interferons and in immune activation research using probiotics as adjuvants, comparable to CpG-DNA through TLR9. The role of the local innate immune system, including pDCs, as the first line of defense against viral infections has gained increasing interest. Moving forward, insight of the immune system and the crosstalk between probiotics and the innate immune system is expected to highlight the role of probiotics in adjunctive immunoregulatory therapy. In combination with drug treatments, probiotics may play a more substantial role in enhancing immune responses. The immunoregulatory approach using probiotics such as LC-Plasma, which can induce anti-infectious factors such as interferons, holds promise as a viable therapeutic and prophylactic option against viral infectious diseases due to their good safety profile and protective efficacy.
Fulltext Immunomodulation resulting of helminth infection could be an opportunity for immunization against tuberculosis and mucosal pathogens

Chin KL, Fonte L, Lim BH, Sarmiento ME, Acosta A

Front Immunol, 2023;14:1091352.
PMID: 37020538 DOI: 10.3389/fimmu.2023.1091352
Fulltext Editorial: Expert opinions and perspectives in immunity to worms infection: 2022

Fonte L, Lim BH, Sarmiento ME, Acosta A

Front Immunol, 2023;14:1210743.
PMID: 37215137 DOI: 10.3389/fimmu.2023.1210743
Fulltext A Direct Role for the CD1b Endogenous Spacer in the Recognition of a Mycobacterium tuberculosis Antigen by T-Cell Receptors

Camacho F, Moreno E, Garcia-Alles LF, Chinea Santiago G, Gilleron M, Vasquez A, et al.

Front Immunol, 2020;11:566710.
PMID: 33162982 DOI: 10.3389/fimmu.2020.566710

Lipids, glycolipids and lipopeptides derived from Mycobacterium tuberculosis (Mtb) are presented to T cells by monomorphic molecules known as CD1. This is the case of the Mtb-specific sulfoglycolipid Ac2SGL, which is presented by CD1b molecules and is recognized by T cells found in tuberculosis (TB) patients and in individuals with latent infections. Our group, using filamentous phage display technology, obtained two specific ligands against the CD1b-Ac2SGL complex: (i) a single chain T cell receptor (scTCR) from a human T cell clone recognizing the CD1b-AcSGL complex; and (ii) a light chain domain antibody (dAbκ11). Both ligands showed lower reactivity to a synthetic analog of Ac2SGL (SGL12), having a shorter acyl chain as compared to the natural antigen. Here we put forward the hypothesis that the CD1b endogenous spacer lipid (EnSpacer) plays an important role in the recognition of the CD1b-Ac2SGL complex by specific T cells. To support this hypothesis we combined: (a) molecular binding assays for both the scTCR and the dAbκ11 antibody domain against a small panel of synthetic Ac2SGL analogs having different acyl chains, (b) molecular modeling of the CD1b-Ac2SGL/EnSpacer complex, and (c) modeling of the interactions of this complex with the scTCR. Our results contribute to understand the mechanisms of lipid presentation by CD1b molecules and their interactions with T-cell receptors and other specific ligands, which may help to develop specific tools targeting Mtb infected cells for therapeutic and diagnostic applications.
Fulltext Frequency and Manifestations of Autoimmunity Among Children Registered in the Kuwait National Primary Immunodeficiency Registry

Massaad MJ, Zainal M, Al-Herz W

Front Immunol, 2020;11:1119.
PMID: 32582199 DOI: 10.3389/fimmu.2020.01119

Objectives: To present a prospective report on the characteristics of autoimmune manifestations in patients with primary immunodeficient children registered in the Kuwait National PIDs Registry (KNPIDR). Methods: The data were obtained from the Kuwait National Primary Immunodeficiency Disorders Registry during the period of January 2004 to December 2019. Results: A total of 286 PID children were registered in KNPIDR during the study period with a predominance of immunodeficiencies affecting cellular and humoral immunity followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Fifty-seven (19.9%) patients presented with a total of 107 autoimmune manifestations. There was no significant statistical association between autoimmune manifestations and gender. Patients with autoimmune manifestations were older at onset of PID symptoms compared to those with no such manifestations, but this did not reach level of significance. The diagnosis delay was longer in patients with autoimmune manifestations compared to those with no such manifestations (p = 0.038). Forty-seven percent of these manifestations were among the presenting symptoms while 53% were documented later during the course of the disease. Fifty-seven percent of the patients developed 1 autoimmune manifestation, 30% developed 2 such manifestations, and 16% had ≥3 autoimmune manifestations. The most common autoimmune manifestation was cytopenia, followed by gastrointestinal manifestations and manifestations of the skin, hair, and nails. Autoimmune cytopenia were more common in patients with immune dysregulation syndromes, while gastrointestinal and skin manifestations predominate in patients with immunodeficiencies affecting cellular and humoral immunity and endocrine manifestations were more common in immune dysregulation syndromes. There were significant statistical associations between developing autoimmune manifestations and death as well as PID categories, being more common in patients with immune dysregulation. The frequency of autoimmunity was high among patients with RAG, WAS, STAT5b, NF-κB2, Fas, FasL, LRBA, APECED, IL-10, and C4 deficiencies. Conclusions: Autoimmunity is frequent in patients with PIDs in Kuwait. This should prompt the suspicion of a PID in patients who present initially with autoimmunity, especially autoimmune cytopenia. Such patients should be managed with extra care since they are at a higher risk of death.
Fulltext Association between alleles, haplotypes, and amino acid variations in HLA class II genes and type 1 diabetes in Kuwaiti children

Dashti M, Nizam R, Jacob S, Al-Kandari H, Al Ozairi E, Thanaraj TA, et al.

Front Immunol, 2023;14:1238269.
PMID: 37638053 DOI: 10.3389/fimmu.2023.1238269

Type 1 diabetes (T1D) is a complex autoimmune disorder that is highly prevalent globally. The interactions between genetic and environmental factors may trigger T1D in susceptible individuals. HLA genes play a significant role in T1D pathogenesis, and specific haplotypes are associated with an increased risk of developing the disease. Identifying risk haplotypes can greatly improve the genetic scoring for early diagnosis of T1D in difficult to rank subgroups. This study employed next-generation sequencing to evaluate the association between HLA class II alleles, haplotypes, and amino acids and T1D, by recruiting 95 children with T1D and 150 controls in the Kuwaiti population. Significant associations were identified for alleles at the HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci, including DRB1*03:01:01, DQA1*05:01:01, and DQB1*02:01:01, which conferred high risk, and DRB1*11:04:01, DQA1*05:05:01, and DQB1*03:01:01, which were protective. The DRB1*03:01:01~DQA1*05:01:01~DQB1*02:01:01 haplotype was most strongly associated with the risk of developing T1D, while DRB1*11:04-DQA1*05:05-DQB1*03:01 was the only haplotype that rendered protection against T1D. We also identified 66 amino acid positions across the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes that were significantly associated with T1D, including novel associations. These results validate and extend our knowledge on the associations between HLA genes and T1D in Kuwaiti children. The identified risk alleles, haplotypes, and amino acid variations may influence disease development through effects on HLA structure and function and may allow early intervention via population-based screening efforts.
Fulltext Primary immunodeficiencies (PID) Life Index in Southeast Asia: A comparative analysis of PID Principles of Care (PoC)

Chan CM, Mahlaoui N, Sánchez Ramón S, Pergent M, Solis L, Prevot J, et al.

Front Immunol, 2023;14:1151335.
PMID: 37063889 DOI: 10.3389/fimmu.2023.1151335

OBJECTIVE: To analyze the implementation of the Principles of Care (PoC) in primary immunodeficiencies (PID) in Southeast Asia (SEA) countries - six years after its call of action.
METHODOLOGY: Using the newly developed PID Life Index software, the index of implementation of principles of care in the management of PIDs patients involving the six participating SEA countries (Cambodia, Indonesia, Malaysia, Vietnam, Thailand, and Philippines) were extracted. For each of the six separate principles, the index from the six countries will be compared and presented based on the calculated index.
RESULTS: Comparative analysis of the six principles of care of PID in the SEA countries showed low diagnostic rate with minimal availability of diagnostic tests options. Generally, almost all SEA countries provide curative treatments, vaccines, and anti-infectious therapies although the reimbursement scheme varied in relieving patients' financial burden. We also highlighted the active involvement of patient organizations in SEA, with main areas of work focused on advocacy and increasing awareness among public and healthcare professionals.
DISCUSSION AND CONCLUSION: It is applaudable that the SEA continent is gradually strengthening its work in management of PID, especially in Thailand and Vietnam. However, more emphasis must be placed among stakeholders in SEA countries towards successful implementation of the PoC for a holistic management of PID patients.
Fulltext Transition practice for primary immunodeficiency diseases in Southeast Asia: a regional survey

Chan CM, Abdul Latiff AH, Noh LM, Ismail IH, Abd Hamid IJ, Liew WK, et al.

Front Immunol, 2023;14:1209315.
PMID: 37529038 DOI: 10.3389/fimmu.2023.1209315

INTRODUCTION: With increased diagnostic capabilities and treatment modalities in the field of primary immunodeficiencies (PID), many pediatric patients survive beyond childhood and experience a change of care to the adult-oriented healthcare system. Unfortunately, the transition pathways for PID are less clearly defined, resulting in deterioration of quality of care in adulthood. Hence, this is the first regional study to address PID clinicians' opinions on practices and challenges of transition care in 7 Southeast Asia (SEA) countries.
METHODS: We adopted a cross-sectional study design through an online survey platform to enquire opinions of transition practices from expert representatives in 7 SEA countries.
RESULTS: Regionally, 3 out 7 countries reported having no practice of transition care. Among cited challenges were reluctant adaptation by patients and caregivers to unfamiliarized adult healthcare systems, inadequate ratio of adult immunologists to patients and lack of facilities for transfer.
DISCUSSION AND CONCLUSION: Our study provides evidence to advocate policy makers on the importance of standardized integration of transition practice towards betterment of transiting PID patients into adulthood.
Fulltext Knowledge, awareness, and perception on genetic testing for primary immunodeficiency disease among parents in Malaysia: a qualitative study

Ahmad Azahari AHS, Hakim Zada F, Ismail IH, Abd Hamid IJ, Lim BWD, Ismail NAS, et al.

Front Immunol, 2023;14:1308305.
PMID: 38283358 DOI: 10.3389/fimmu.2023.1308305

BACKGROUND: Primary Immunodeficiency Disease (PID), also known as Inborn Errors of Immunity (IEI), comprises a group of rare genetic disorders that impair the body's immune responses. These conditions result from monogenic germline mutations that affect the function of genes governing the innate and adaptive immune system. Therefore, individuals with PID are more susceptible to infectious diseases, allergies, and autoimmune and autoinflammatory conditions. The prevalence of PID has been on the rise, with the number of classified diseases reaching 404, and 430 genetic defects reported to cause these conditions. However, in Malaysia, genetic testing for PID is currently limited and needs to be outsourced to overseas laboratories, posing financial challenges for families. Moreover, limited research has focused on the knowledge and awareness of genetic testing among parents of children with PID in Malaysia. This study aims to address this gap and provide valuable insights into the knowledge, awareness, and perception of genetic testing among this specific population.
METHOD: This qualitative cross-sectional study utilised online open-ended, semi-structured focus group interviews to explore the perceptions and experiences of parents of children with Primary Immunodeficiency (PID). Participants were recruited through convenience sampling from the Malaysian Patient Organisation for Primary Immunodeficiencies (MyPOPI), a non-governmental organisation dedicated to providing support and raising awareness about PID. The study spanned from May 2023 to July 2023 and included participants from diverse regions of Malaysia who had undergone different diagnostic journeys in various hospitals.
RESULT: The focus group discussions yielded 11 sub-themes that highlighted the experiences, understanding and challenges of the participants regarding genetic testing based on the semi-structured questions. These sub-themes were then grouped into four main themes that are awareness and understanding of genetic testing, the journey towards diagnosis and treatment, emotional impact and psychological factors, and the importance of medical experts in diagnosing and managing PID, as well as public perception and awareness.
CONCLUSION: In conclusion, this study highlights the diverse knowledge, awareness, and perception surrounding genetic testing for PID. Factors such as access to services, family history, and personal circumstances shape individuals' understanding of genetic testing. The importance of healthcare professionals, along with the need for improved accessibility and targeted communication strategies, is underscored to enhance understanding and reduce stigma surrounding genetic testing for rare diseases like PID.
Fulltext Parents' and healthcare professionals' perception toward the introduction of a new fully liquid hexavalent vaccine in the Malaysian national immunization program: a cross-sectional study instrument development and its application

Al Bashir L, Ismail A, Aljunid SM

Front Immunol, 2023;14:1052450.
PMID: 37180162 DOI: 10.3389/fimmu.2023.1052450

A newly developed fully liquid hexavalent vaccine that comprises six antigens for Diphtheria, Tetanus, acellular Pertussis, Inactivated Poliomyelitis, Haemophilus Influenza type b., and Hepatitis B, is proposed to be introduced in the Malaysian national immunization program, instead of the non-fully liquid pentavalent vaccine and monovalent Hepatitis B vaccine that is currently employed in the immunization schedule. Although the introduction of new vaccines is a necessary intervention, it still needs to be accepted by parents and healthcare professionals. Hence, this study aimed to develop three structured questionnaires and to investigate the participants' perception and acceptability toward the incorporation of the new fully liquid hexavalent vaccine. A cross-sectional study was conducted among a sample of 346 parents, 100 nurses, and 50 physicians attending twenty-two primary health care centers in the states of Selangor and the Federal Territory of Kuala Lumpur and Putrajaya during 2019-2020. The study found that Cronbach's alpha coefficients for the study instruments ranged from 0.825 to 0.918. Principal components analysis produced a good fit with KMO>0.6. For the parents' perception questionnaire, the only extracted factor explained 73.9 % of the total variance; for the nurses' perception toward a non-fully and fully liquid combined vaccine, there was a sole extracted factor that explained 65.2 % and 79.2% of the total variance, respectively. Whereas for the physicians' perception, there was one factor extracted that explains 71.8 % of the total variance. The median score for all the questionnaire items ranged from 4 to 5 (Q1 and Q3 vary between 3-5). Parents' ethnicity was significantly associated (P-value ≤ 0.05) with the perception that the new hexavalent vaccine would reduce their transportation expenses. Moreover, a significant association (P-value ≤ 0.05) was found between physicians' age and the perception of the hexavalent vaccine's ability to decrease patient overcrowding in primary healthcare centers. The instruments used in this study were valid and reliable. Parents of Malay ethnicity were the most concerned about transportation expenses since they have the lowest income and are more concentrated in rural areas compared to other races. Younger physicians were concerned about reducing patient crowding and hence reducing their workload and burnout.
Fulltext Negative Checkpoint Regulatory Molecule 2B4 (CD244) Upregulation Is Associated with Invariant Natural Killer T Cell Alterations and Human Immunodeficiency Virus Disease Progression

Ahmad F, Shankar EM, Yong YK, Tan HY, Ahrenstorf G, Jacobs R, et al.

Front Immunol, 2017;8:338.
PMID: 28396665 DOI: 10.3389/fimmu.2017.00338

The CD1d-restricted invariant natural killer T (iNKT) cells are implicated in innate immune responses against human immunodeficiency virus (HIV). However, the determinants of cellular dysfunction across the iNKT cells subsets are seldom defined in HIV disease. Herein, we provide evidence for the involvement of the negative checkpoint regulator (NCR) 2B4 in iNKT cell alteration in a well-defined cohort of HIV-seropositive anti-retroviral therapy (ART) naïve, ART-treated, and elite controllers (ECs). We report on exaggerated 2B4 expression on iNKT cells of HIV-infected treatment-naïve individuals. In sharp contrast to CD4(-)iNKT cells, 2B4 expression was significantly higher on CD4(+) iNKT cell subset. Notably, an increased level of 2B4 on iNKT cells was strongly correlated with parameters associated with HIV disease progression. Further, iNKT cells from ART-naïve individuals were defective in their ability to produce intracellular IFN-γ. Together, our results suggest that the levels of 2B4 expression and the downstream co-inhibitory signaling events may contribute to impaired iNKT cell responses.
Fulltext Could Perturbation of Gut Microbiota Possibly Exacerbate the Severity of COVID-19 via Cytokine Storm?

Vignesh R, Swathirajan CR, Tun ZH, Rameshkumar MR, Solomon SS, Balakrishnan P

Front Immunol, 2020;11:607734.
PMID: 33569053 DOI: 10.3389/fimmu.2020.607734
Fulltext Development of a Bioinformatics Framework for Identification and Validation of Genomic Biomarkers and Key Immunopathology Processes and Controllers in Infectious and Non-infectious Severe Inflammatory Response Syndrome

Tong DL, Kempsell KE, Szakmany T, Ball G

Front Immunol, 2020;11:380.
PMID: 32318053 DOI: 10.3389/fimmu.2020.00380

Sepsis is defined as dysregulated host response caused by systemic infection, leading to organ failure. It is a life-threatening condition, often requiring admission to an intensive care unit (ICU). The causative agents and processes involved are multifactorial but are characterized by an overarching inflammatory response, sharing elements in common with severe inflammatory response syndrome (SIRS) of non-infectious origin. Sepsis presents with a range of pathophysiological and genetic features which make clinical differentiation from SIRS very challenging. This may reflect a poor understanding of the key gene inter-activities and/or pathway associations underlying these disease processes. Improved understanding is critical for early differential recognition of sepsis and SIRS and to improve patient management and clinical outcomes. Judicious selection of gene biomarkers suitable for development of diagnostic tests/testing could make differentiation of sepsis and SIRS feasible. Here we describe a methodologic framework for the identification and validation of biomarkers in SIRS, sepsis and septic shock patients, using a 2-tier gene screening, artificial neural network (ANN) data mining technique, using previously published gene expression datasets. Eight key hub markers have been identified which may delineate distinct, core disease processes and which show potential for informing underlying immunological and pathological processes and thus patient stratification and treatment. These do not show sufficient fold change differences between the different disease states to be useful as primary diagnostic biomarkers, but are instrumental in identifying candidate pathways and other associated biomarkers for further exploration.
Fulltext Gut Immune System and the Implications of Oral-Administered Immunoprophylaxis in Finfish Aquaculture

Lee PT, Yamamoto FY, Low CF, Loh JY, Chong CM

Front Immunol, 2021;12:773193.
PMID: 34975860 DOI: 10.3389/fimmu.2021.773193

The gastrointestinal immune system plays an important role in immune homeostasis regulation. It regulates the symbiotic host-microbiome interactions by training and developing the host's innate and adaptive immunity. This interaction plays a vital role in host defence mechanisms and at the same time, balancing the endogenous perturbations of the host immune homeostasis. The fish gastrointestinal immune system is armed with intricate diffused gut-associated lymphoid tissues (GALTs) that establish tolerance toward the enormous commensal gut microbiome while preserving immune responses against the intrusion of enteric pathogens. A comprehensive understanding of the intestinal immune system is a prerequisite for developing an oral vaccine and immunostimulants in aquaculture, particularly in cultured fish species. In this review, we outline the remarkable features of gut immunity and the essential components of gut-associated lymphoid tissue. The mechanistic principles underlying the antigen absorption and uptake through the intestinal epithelial, and the subsequent immune activation through a series of molecular events are reviewed. The emphasis is on the significance of gut immunity in oral administration of immunoprophylactics, and the different potential adjuvants that circumvent intestinal immune tolerance. Comprehension of the intestinal immune system is pivotal for developing effective fish vaccines that can be delivered orally, which is less labour-intensive and could improve fish health and facilitate disease management in the aquaculture industry.
Fulltext Primary Immunodeficiencies: A Decade of Progress and a Promising Future

Meyts I, Bousfiha A, Duff C, Singh S, Lau YL, Condino-Neto A, et al.

Front Immunol, 2020;11:625753.
PMID: 33679719 DOI: 10.3389/fimmu.2020.625753
Fulltext Spectrum of Viral Infections Among Primary Immunodeficient Children: Report From a National Registry

Al-Herz W, Essa S

Front Immunol, 2019;10:1231.
PMID: 31191561 DOI: 10.3389/fimmu.2019.01231

Objective: To present the frequency and spectrum of viral infections in primary immunodeficient children. Methods: The data was obtained from the Kuwait National Primary Immunodeficiency Disorders (PIDs) Registry during the period of 2004-2018. Results: A total of 274 PID children were registered in KNPIDR during the study period with predominance of immunodeficiencies affecting cellular and humoral immunity, followed by combined immunodeficiencies with associated syndromic features and diseases of immune dysregulation. Overall infectious complications affected 82.4% of the patients, and viral infections affected 31.7% of the registered patients. Forty-five patients (16.4%) developed viral infections caused by at least 2 organisms, among those 20 patients were affected by three or more viral infections. There was a statistically significant association between viral infections and PID category. However, there was no statistically significant association between viral infections and gender or the patients' onset age. There was a total of 170 viral infections during the study period and the causes of these infections were predominated by CMV (22.2%), adenovirus (11.7%), EBV (11.1%), and enteroviruses (7.4%). CMV and parainfluenza infections were more common in the group of immunodeficiencies affecting cellular and humoral immunity while EBV and human papilloma virus (HPV) were more common in the immune dysregulation group and combined immunodeficiencies with associated syndromic features, respectively. The most common presentation was viremia (28.8%) followed by pneumonia (28.2%) and skin infections (17.6%). The most common causes of viremia were CMV followed by adenovirus and EBV, while the most common organisms causing pneumonia were CMV followed by rhinovirus and parainfluenza. There were 80 deaths among the registered patients, 10% were caused by viral infections. Conclusions: Viral infections are common in PIDs and result into a wide-range of clinical manifestations causing significant morbidity and mortality.
Fulltext Psychological Stresses in Children Trigger Cytokine- and Kynurenine Metabolite-Mediated Abdominal Pain and Proinflammatory Changes

Myint K, Jacobs K, Myint AM, Lam SK, Lim YA, Boey CC, et al.

Front Immunol, 2021;12:702301.
PMID: 34539633 DOI: 10.3389/fimmu.2021.702301

Recurrent abdominal pain (RAP) is a common medically unexplained symptom among children worldwide. However, the biological mechanisms behind the development of functional and behavioral symptoms and changes in blood markers have not been well explored. This study aimed to assess changes in the concentrations of inflammatory markers, including cytokines and tryptophan catabolites, in the serum of children with RAP compared to those with subclinical infections. Children with RAP but without organic diseases were included, and those with asymptomatic intestinal parasitic infections were used as a subclinical infection cohort. Blood samples were collected and used to measure the cytokine profile using Multiplex Immunoassay and tryptophan catabolites using high performance liquid chromatography. Children with RAP showed significantly higher concentrations of serum tumor necrotic factor-α, p<0.05, but lower concentrations of IL-10, p<0.001, IL-6, p<0.001 and brain-derived neurotrophic factors (BDNF) p<0.01. In addition, a significant increase in the metabolite of the kynurenine pathway, 3-hydroxyanthranilic acid (3-HAA) p<0.01, a significant decrease in the concentrations of anthranilic acid (AA) p<0.001, together with an increased ratio of serum 3-HAA to AA (3-HAA/AA) p<0.001, was found in this cohort. These findings indicate the significant activation of the immune system and presence of inflammation in children with RAP than those with subclinical parasitic infections. Moreover, children with RAP tested with the Strengths and Difficulties Questionnaire (SDQ), displayed high psychological problems though these SDQ scores were not statistically associated with measured cytokines and kynurenine metabolites. We however could hypothesize that the pro-inflammatory state together with concomitant low concentrations of BDNF in those children with RAP could play a role in psychological stress and experiencing medically unexplained symptoms.
Fulltext Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

Islam MA, Khandker SS, Kotyla PJ, Hassan R

Front Immunol, 2020;11:1477.
PMID: 32793202 DOI: 10.3389/fimmu.2020.01477

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.

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