American journal of clinical and experimental immunology最新文献

A particular group of children developed severe multisystem inflammation associated with current or recent SARS-CoV-2 infection or contact with a COVID-19 patient in the previous few weeks. The condition was defined as multisystem inflammatory syndrome (MIS) in children (MIS-C). As the definition of CDC and WHO is fast widely accepted, the lack of an international consensus on the definition of the syndrome cases, however, leads to some difficulties for clinicians. Additionally, MIS-C shares some immunological, pathological features with the conditions, such as cytokine storm, long COVID and/or post-COVID syndrome. The picture is further complicated by the existence of the syndrome in adults (MIS-A). Therefore, we have compared these conditions from the immunological point of view in our review based on the published case reports, studies, systematic reviews and metaanalyses. This knowledge is essential not only for immunologists. The paediatricians must be familiar with the immunological bases of the syndrome and implement it in on-time recognition and diagnosis and minimize systemic damage of this life-threatening condition at the earliest stage possible. Further investigations still need to be done to find and develop the best effective therapy and prophylactics.

Objectives: Rheumatoid arthritis (RA) is a chronic autoimmune disease, that involves both pro- and anti-inflammatory mechanisms. The purpose of the present study is to investigate T-cell immunoglobulin and mucin domain 3 (Tim-3) in RA.

Methods: Plasma levels of soluble (s) Tim-3 in early RA (n=98), were followed, to evaluate association with treatment and disease activity, acquired from a prospective collected biobank (clinicaltrials.gov (NCT00660647)). We also investigate the influence of Tim-3 on spontaneous cytokine production in synovial fluid mononuclear cells (SFMC) from RA patients after addition of neutralizing anti-Tim-3's antibodies, either alone or in combination with neutralizing anti-Programmed Cell death protein 1 (PD-1) antibodies.

Results: Long-time stimulated CD4 T-cells expressed high levels of Tim-3, but tended to decrease their PD-1 expression. Tim-3 expression was exclusively seen co-expressed with PD-1 by CD3, CD4, CD45RO positive cells in the inflamed RA joint. Addition of neutralizing Tim-3 antibodies increased the secretion of IFNγ and MCP-1, in SFMC cultures from RA. Whereas neutralizing anti-PD-1 antibodies showed a broader impact on cytokine production. Finally, we observed that soluble Tim-3 is increased in plasma and is associated with disease activity in early RA.

Conclusion: Taken together, our findings indicate disease-suppressive functions of Tim-3 in RA.

The pathogenesis of the severity of chikungunya infection is not yet fully understood.

Objective: To assess the role of the cytokines/chemokines and system of complement in the evolution of chikungunya infection.

Methods: In both acute and chronic phases, we measured the serum levels of 12 cytokines/chemokines and two complement mediators: mannose-binding lectin (MBL) and C3a, in 83 patients with chikungunya infection and ten healthy controls.

Results: During the acute phase, 75.9% of the patients developed musculoskeletal disorders, and in 37.7% of them, these disorders persisted until the chronic phase. In general, patients had higher levels of cytokines than healthy controls, with significant differences for IFN-γ, IL-6, IL-8, IL-10, and MIP-1. Most cytokines exhibited a downward trend during the chronic phase. However, only IL-10, and MIP-1 levels were significantly lower in the chronic phase. Additionally, these levels never decreased to concentrations found in healthy controls. Moreover, MBL levels were significantly higher in the acute phase compared with the chronic phase. C3a levels were significantly higher in patients with musculoskeletal disorder compared with patients without it, in both acute-phase 118.2 (66.5-252.9), and chronic phase 68.5 (64.4-71.3), P < 0.001. Interestingly, C3a levels were significantly higher when patients had a severe disease version. Besides, in the acute phase, C3a levels were higher in patients that suffer arthritis as opposed to when they suffer arthralgia, 194.3 (69.5-282.2), and 70.9 (62.4-198.8), P = 0.013, respectively.

Conclusions: Our results showed an immunological response that persisted until the chronic phase and the role of the complement system in the severity of the disease.

Background: Idiopathic chronic obstructive pulmonary disease (ICOPD) is a prevalent human disease. The etiology of the disease is yet to be clarified. The main aim of this project was to explore serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) in the ICOPD patients in comparison to healthy controls.

Methods: In this cross-sectional study, serum levels of IL-6, TNF-α and TGF-β were evaluated in the 70 non-smoker ICOPD patients and 70 sex and age matched controls, using ELISA technique by the commercial kits from Karmania Pars Gene Company. Analysis of data was performed by parametric independent and Pearson correlation test.

Results: Serum levels of IL-6 and TGF-β, but not TNF-α, were significantly decreased in the ICOPD patients in comparison to controls. Serum levels of IL-6, TNF-α and TGF-β were not altered in the ICOPD male in comparison to female and also in mild when compared to moderate ICOPD patients.

Conclusions: Down-regulation of TGF-β may be the main risk factor for deterioration of inflammation in the ICOPD patients. Decreased IL-6 may be related to the idiopathic type of COPD.

Background: There are insufficient data concerning COVID-19 severity among asthmatic children.

Aim: to evaluate the impact of asthma on COVID-19 severity and outcome.

Patients and methods: We carried out an observational study that comprised 2 matched groups of children with confirmed/probable COVID-19: 30 with and 32 without asthma aged 6-18 years, who were enrolled consecutively from Children's Hospital, Ain Shams University, Egypt. COVID-19 clinical presentations, laboratory and radiological abnormalities, severity and outcome were compared between the 2 groups. Asthma severity and control were assessed based on GINA 2020.

Results: The asthmatic COVID-19 children were 9 boys and 21 girls, with median age 9 years, IQR: 8-12 years. The non-asthmatic COVID-19 group included 18 males and 14 females with median age 9.5 years, IQR: 7-12.5 years. Clinical manifestations of COVID-19 were comparable among the 2 groups, except for wheezes which were more frequently encountered as a COVID-19 manifestation among the asthmatics (p=0.001). Multisystem inflammatory syndrome (MIS-c) was diagnosed in one asthmatic and 3 non-asthmatic patients. The asthmatic group had higher frequency of serum ferritin, LDH and D-dimer elevations compared to the non-asthmatic peers (p values 0.014, 0.001, and 0.015 respectively). Based on CO-RAD classification, 70% of the asthmatic patients had CO-RAD score of 5 versus 6.3 % among the non-asthmatic group with significant differences between the 2 groups in their CO-RAD scores (P=0.002). COVID-19 severity was comparable among the studied groups (P=0.775), as well as COVID-19 outcome and duration of hospital stay (p values 0.999, and 0.655, respectively).

Conclusion: From our limited sample sized study, childhood asthma did not pose a significant impact on COVID-19 severity and outcome. Further longitudinal studies are warranted to validate our conclusion and investigate the relation of COVID-19 severity and outcome to allergen immunotherapy and the use of biologicals for asthma treatment.

Background: definite figures of allergy to wheat and strawberries in Egypt are lacking. We investigated IgE-mediated sensitization to wheat and strawberry among a group of allergic children, and the relation between wheat and strawberry sensitization.

Patients and methods: This study comprised 256 children, with physician-diagnosed allergy: bronchial asthma (98 patients), allergic rhinitis (28 patients), atopic dermatitis (53 patients) and food allergy (10 patients). Sensitization to wheat and strawberry was assessed using prick testing, followed by oral challenge test to prove allergy.

Results: Wheat sensitization was observed in 9.4% of the studied children with confirmed allergy in 0.4%. Strawberry sensitization was observed in 7.8% of patients, with 2% confirmed allergy. Either sensitization did not influence response of allergy to treatment. Wheat and strawberry sensitizations were positively correlated.

Conclusion: Wheat and strawberry allergies are not common among Egyptian children with allergic disorders; and did not impact the response to allergy treatment.

Breast cancer is the most frequently happening cancer and the most typical cancer death among females. Despite the crucial progress in breast cancer therapy by using Chemotherapeutic agents, most anti-tumor drugs are insufficient to destroy exactly the breast cancer cells. The noble method of drug delivery using nanoparticles presents a great promise in treating breast cancer most sufficiently and with the least harm to the patient. Nanoparticles, with their spectacular characteristics, help overcome problems of this kind. Unique features of nanoparticles such as biocompatibility, bioavailability, biodegradability, sustained release, and, most importantly, site-specific targeting enables the Chemotherapeutic agents loaded in nanocarriers to differentiate between healthy tissue and cancer cells, leading to low toxicity and fewer side effects. This review focuses on evaluating and comprehending nanoparticles utilized in breast cancer treatment, including the most recent data related to the drugs they can carry. Also, this review covers all information related to each nanocarrier, such as their significant characteristics, subtypes, advantages, disadvantages, and chemical modification methods with recently published studies. This article discusses over 21 nanoparticles used in breast cancer treatment with possible chemical ligands such as monoclonal antibodies and chemotherapeutic agents binding to these carriers. These different nanoparticles and the unique features of each nanocarrier give the researchers all the data and insight to develop and use the brand-new drug delivery system.

Background: The pretreatment of dexamethasone on the efficacy and immune-related adverse events of immunotherapy involving programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PDL1) inhibitors is an effective option for the first-line treatment of advanced non-small-cell lung cancer (NSCLC). With the immunosuppressive effect, corticosteroids may be used to reduce the efficacy of PDL1 blockade, as well as prevent overactive immune responses, thereby reducing the occurrence of immune-related adverse events (irAEs). This study quantitatively summarized the current evidence, and compared the efficacy and toxicity of therapies involving chemotherapy plus PDL1 inhibitors plus dexamethasone pretreatment (I+C+D) with chemotherapy plus PDL1 inhibitors (I+C) and therapies involving PDL1 inhibitors or chemotherapy alone (I or C).

Methods: The protocol of this study was registered with PROSPERO (CRD42021227281). By using a network meta-analysis approach, the different treatments were compared and ranked based on their effectiveness and rates of irAEs at the different grades. Risk rates were determined through direct meta-analysis and indirect treatment comparison.

Results: 12 randomized clinical trials were included with a total of 7155 NSCLC patients. Network meta-analysis generated 15 comparisons. The combination treatment of I+C+D showed a longer progression-free survival and overall survival, while I+C was less toxic, and the toxicity of I+C+D or that of I+C had been significantly decreased, compared to that of monotherapy with either drug. According to the ranking analysis, I+C+D is consistently proved to be the most effective therapeutic strategy, while I+C is linked to the lowest rate of irAEs, with the rate of grade value of ≥3 irAEs.

Conclusion: The combination treatment of I+C+D is the most effective approach for the first-line treatment of NSCLC patients treated with I+C, I, or C.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with wide spectrum of symptoms and few effective therapies. Evidence is suggestive of an association between immune system dysfunction and autism spectrum disorders (ASD) among children with ASD. Immunoglobulins (Ig) are found to be increased in the circulation of individuals with autism. The prospective study was aimed to estimate and correlate the levels of IgG4 in blood and saliva of children with autism.

Methodology: Blood and unstimulated saliva were collected from 172 children (55 ASD, 57 healthy control, and 60 suspected parasitic infection) aged 0-18 years. Routine blood investigations were done. Serum and salivary IgG4 levels were analyzed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Data were subjected to statistical analysis.

Results: ELISA tests showed that the IgG4 levels in serum and saliva were significantly increased (P<0.05) in children with ASD as compared to normal control children. Both serum and saliva IgG4 levels showed a significant positive correlation (P<0.05).

Conclusion: IgG4 can be used as a potential biomarker for the early detection of ASD. Further, saliva can be a diagnostic, noninvasive assessment tool for health monitoring of children with autism. Lay summary: The collection of saliva is easy and painless compared to other sample collection methods. The present study shows that, among children with autism, brain-reactive antibody, immunoglobulin G4 (gG4), is increased both in blood and saliva, and there is a significant correlation between the two levels. Therefore, the study recommends IgG4 as a potential biomarker for the early detection of autism, and saliva can be helpful in diagnosis and health monitoring of children with ASD.

Background: IgA deficiency is the most common immunodeficiency disorder. Most affected individuals are asymptomatic, and since there are no routine diagnostic screening programs the prevalence of this disease has remained uncertain.

Methods and materials: Seven thousand blood donors who attended Fars Blood Transfusion Center, from September 2017 to March 2018, were selected randomly, and their serum IgA levels were checked by Immunoturbidimetry method. Cases with IgA levels <10 mg/dL were considered as serum IgA deficient patients. Serum IgM and IgG levels of IgA deficient cases were measured to determine selective IgA deficiency. The prevalent clinical findings of IgA deficiency were also investigated.

Results: Ten blood donors had selective IgA deficiency: 0.14% (CI 95%: 0.001, 0.002). All cases were male, with a mean age of 36.10±9.70 years. Investigating common clinical findings in the IgA deficient cases revealed the most prevalent symptoms were recurrent upper respiratory tract infections (50%) which were significantly higher in the study group compared to the control group (P-value =0.008) and allergic disorders (40%) with no statistical difference from the control cases.

Conclusion: The prevalence of selective IgA deficiency (SIgAD) among blood donors at Fars Transfusion Center was 0.14%. The most common clinical finding among the patients with SIgAD was recurrent upper respiratory infections, followed by allergic diseases.