IgE to wheat, prick test, and Patch test among children with celiac disease.

INTRODUCTION AND AIM: Celiac disease is one of the most common autoimmune disorders. This study aimed to evaluate the relationship between celiac disease and wheat sensitization. SUBJECTS AND METHODS: In the current study, children aged < 18 years with confirmed celiac disease were included. Data were analyzed using SPSS. RESULTS: Gastrointestinal problems were the most common indication for evaluation in terms of celiac disease. Prick and patch tests were positive in 43.4% and 34% respectively. CONCLUSION: Prick test and patch test for wheat sensitization were positive in about 30-45% of the children for celiac disease.

The molecular fingerprint of neuroinflammation in COVID-19: A comprehensive discussion on molecular mechanisms of neuroinflammation due to SARS-COV2 antigens.

BACKGROUND AND OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 attacks the neural system directly and indirectly via various systems, such as the nasal cavity, olfactory system, and facial nerves. Considering the high energy requirement, lack of antioxidant defenses, and high amounts of metal ions in the brain, oxidative damage is very harmful to the brain. Various neuropathic pain conditions, neurological disorders, and neuropsychiatric complications were reported in Coronavirus disease 2019, prolonged Coronavirus disease 2019, and after Coronavirus disease 2019 immunization. This manuscript offers a distinctive outlook on the interconnectedness between neurology and neuropsychiatry through its meticulous analysis of complications. DISCUSSION: After recovering from Coronavirus disease 2019, approximately half of the patients reported developing Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Long Coronavirus disease 2019 imaging reports illustrated the hypometabolism in various parts of the brain, such as olfactory bulbs, limbic/paralimbic domains, the brainstem, and the cerebellum. Ninety imaging and neuropathological studies of Coronavirus disease 2019 have shown evidence of white matter, brainstem, frontotemporal, and oculofrontal lesions. Emotional functions, such as pleasant, long/short-term memory, movement, cognition and cognition in decision-making are controlled by these regions. The neuroinflammation and the mechanisms of defense are well presented in the discussion. The role of microglia activation, Inducible NO synthase, Cyclooxygenases ½, Reactive oxygen species, neurotoxic toxins and pro-inflammatory cytokines, such as Interleukin-1 beta, Interleukin-6 and Tumor Necrosis Factor-alpha are highlighted in neuronal dysfunction and death. Nuclear factor kappa-light-chain-enhancer of activated B cells, Mitogen-activated protein kinase, Activator Protein 1, and Interferon regulatory factors are the main pathways involved in microglia activation in Coronavirus disease 2019 neuroinflammation. CONCLUSION: The neurological aspect of Coronavirus disease 2019 should be highlighted. Neurological, psychological, and behavioral aspects of Coronavirus disease 2019, prolonged Coronavirus disease 2019, and Coronavirus disease 2019 vaccines can be the upcoming issues. We need a global awareness where this aspect of the disease should be more considered in health research.

Implications of Complement Imbalance in COVID-19: A Molecular Mechanistic Discussion on the Importance of Complement Balance.

Two central questions in COVID-19 treatment which should be considered are: "How does the imbalance of the complement system affect the therapeutic approaches?" and "Do we consider complement inhibitors in therapeutic protocols?". The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms "COVID-19", "Complement", "Complement inhibitor", "SARS-CoV-2", and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in "KEGG pathway database". Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors.

Regulatory factors involved in Th17/Treg cell balance of immune thrombocytopenia.

Immune thrombocytopenia is a common heterogeneous autoimmune disease that is characterized by decreasing peripheral blood platelet counts and increasing risk of bleeding. Studies have shown that an imbalance between T helper 17 (Th17) and Regulatory T (Treg) cells differentiated from CD4+T-cells is a key factor influencing the development and pathogenesis of immune thrombocytopenia. Th17 cells promote the development of chronic inflammatory disorders and induce autoimmune diseases, whereas Treg cells regulate immune homeostasis and prevent autoimmune diseases. Several regulators affecting the production and maintenance of these cells are also essential for proper regulation of Th17/Treg balance; these regulatory factors include cell surface proteins, miRNAs, and cytokine signaling. In this review, we focus on the function and role of balance between Th17 and Treg cells in immune thrombocytopenia, the regulatory factors, and therapeutic goals of this balance in immune thrombocytopenia.

Oral Immunotherapy in Patients with IgE Mediated Reactions to Egg White: A Clinical Trial Study.

BACKGROUND: Oral immunotherapy (OIT) is under consideration as a promising treatment for desensitization of egg-allergic patients. The objective of this study was to assess the effectiveness of egg-white OIT in patients with IgE-mediated allergy to egg white and to compare the clinical and laboratory findings before and after OIT. METHODS: This clinical trial was performed from February to August 2018 in Rasool e Akram Hospital, Tehran, Iran. Patients' selection criteria included a history of allergic symptoms, skin prick test (SPT) reactivity to egg white, and the inability to pass the Oral Food Challenge (OFC). Egg-white OIT was done for eight patients in the OIT group for 6 months while egg-white-free products were administrated for controls. The SPT reactivity, specific IgE, and IgG4 for egg white and ovomucoid were evaluated before and after OIT. RESULTS: Hundred percent of the subjects in OIT group were desensitized and tolerated 40 cc raw egg white following 6-month maintenance whereas none of the controls was able to pass the OFC. The findings obtained from the evaluations indicated a significant decrease in the wheal size and specific IgE to egg white after OIT (P = .001). Furthermore, a significant decrease of IgE/IgG4 ratio to egg white was found in OIT group (P = .01). CONCLUSION: This OIT protocol was successful as all OIT patients were able to continue 6-month OIT process and the reaction threshold to egg white increased in the OIT group. Therefore, it could be regarded as an effective and safe protocol to treat egg-allergic patients.

A randomized clinical trial evaluating the immunomodulatory effect of convalescent plasma on COVID-19-related cytokine storm.

Evaluating the effect of convalescent plasma (CP) on some cytokine storm indices in severe COVID-19 patients. Totally, 62 patients were randomly assigned into two groups for this clinical trial. Patients in the intervention group received one unit (500 mL) plasma on the admission day plus standard drugs while the controls merely received standard treatments. Eventually, primary and secondary outcomes were evaluated. In the CP group, compared with controls, the mean levels of lymphocytes and IL-10 significantly increased while the levels of IL-6, TNF-α, and IFN-γ decreased (p < 0.05). The length of in-hospital stay, and mortality rate did not significantly reduce in the CP group compared with controls (p > 0.05) while WHO severity scores remarkably improved (p = 0.01), despite the higher frequency of underlying diseases among the CP group (66.7%) vs. controls (33.3%). Although CP has a remarkable immunomodulatory and antiviral potential to improve the cytokine storm and disease severity in COVID-19 patients, it did not considerably affect the mortality rate.

Innate and Adaptive Immunity Imbalance With Severe COVID-19 Pneumonia in Children and Adults.

Introduction: Little is known about the laboratory and radiological characteristics and clinical significance of peripheral immune alterations in patients with coronavirus disease 2019 (COVID-19). This study aims to clarify these aspects in children and adults with COVID-19. Methods: In this consecutive pilot study, COVID-19 patients with the confirmed pneumonia and real-time RT-PCR were recruited prospectively in June 2020. The clinical, chest CT, and laboratory features, such as lymphocyte subpopulations, were analyzed for each individual. Results: Forty confirmed COVID-19 patients, 11 severe children, 12 severe adults, and 17 critical adult patients, besides 20 healthy pediatrics and 14 healthy adults as controls, were enrolled prospectively. Adult patients, especially critical ones, had a much higher prevalence of laboratory and chest CT abnormalities. Data regarding immune cell subsets in children patients, compared with matched controls, had higher CD3+ CD8+ T cells (p = 0.004) and lower CD4+/CD8+ ratio (p = 0.042), while adult patients, compared with matched controls, had lower CD14+ monocytes (p = 0.032). Adult patients were also categorized as experiencing critical or severe illness on admission and, compared with severe patients, had lower total lymphocytes (p < 0.047), CD3+ T-lymphocytes (p < 0.002), and CD3+ CD8+ T cells (p = 0.001) and, on the other hand, had higher CD3+ CD4+ T cells (p = 0.012) and CD4+/CD8+ ratio (p = 0.003). Non survived adults, compared with survived patients, had significantly lower CD3+ T-lymphocyte (p = 0.005). Conclusion: Unlike adult patients, who compared with matched controls and had more comorbidities, higher frequency of severe clinical symptoms, laboratory abnormalities, and immune cells alteration, clinical manifestations of COVID-19 in children (compared with matched controls) were relatively mild, and fewer clinical complications were seen either, perhaps because of a milder inflammatory response following their peripheral innate and adaptive immune cell alteration pattern.

X-linked hyper-IgM syndrome associated with pulmonary manifestations: A very rare case of functional mutation in CD40L gene in Iran.

Hyper IgM (HIGM) syndromes are a complex of primary immunodeficiency disorders. A 4-years-old boy with recurrent fever and chills, dyspnea, sort throat for a month was admitted to emergency department. In the current case, whole exome sequencing followed by Sanger sequencing were employed in order to screen probable functional mutations. Molecular analysis revealed a functional mutation across the CD40L gene (NM_000074: exon5: c.T464C) resulted in amino acid change p.L155P attributed to X-linked hyper IgM syndrome. The findings of the current study signify the critical role of microbial infection as well as XHIGM screening, particularly in those children cases with respiratory symptoms.

Colonization and antifungals susceptibility patterns of Candida species isolated from hospitalized patients in ICUs and NICUs.

BACKGROUND: Several studies have shown that there are an increasing in invasive candidiasis during 2-3 last decades. Although, Candida albicans is considered as the most common candidiasis agents, other non-albicans such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis were raised as infectious agents. Resistance to fluconazole among non-albicans species is an important problem for clinicians during therapy and prophylaxis. OBJECTIVES: The aim of current study was to detect the Candida species from hospitalized neonatal and children in intensive care units (ICUs) and neonatal intensive care units (NICUs). In addition, the susceptibility of isolated agents were also evaluated against three antifungals. MATERIALS AND METHODS: In the present study 298 samples including 98 blood samples, 100 urines and 100 swabs from oral cavity were inoculated on CHROMagar Candida. Initial detection was done according to the coloration colonies on CHROMagar Candida . Morphology on cornmeal agar, germ tube formation and growth at 45°C were confirmed isolates. Amphotericin B, fluconazole and terbinafine (Lamisil) were used for the susceptibility tests using microdilution method. RESULTS: In the present study 21% and 34% of urines and swabs from oral cavity were positive for Candida species, respectively. The most common species was C. albicans (62.5%) followed by C. tropicalis (15.6%), C. glabrata (6.3%) and Candida species (15.6%). Our study indicated that the most tested species of Candida, 70.3% were sensitive to fluconazole at the concentration of ≤8 µg/mL. Whereas 9 (14.1%) of isolates were resistant to amphotericine B at ≥8 µg/mL. CONCLUSIONS: This study demonstrates the importance of species identification and antifungals susceptibility testing for hospitalized patients in ICUs and NICUs wards.

Distribution of haematological indices among subjects with Blastocystis hominis infection compared to controls.

INTRODUCTION: Some studies suggest Blastocystis hominis is a potentially pathogenic protozoa. Blastocystis hominis contributed to anaemia in children aged 8-10 years old in one study. AIM: To compare haematological indices in cases with blastocystis hominis infection with healthy controls. MATERIAL AND METHODS: From 2001 to 2012, 97600 stool examinations were done in 4 university hospitals. Parasites were observed in 46,200 specimens. Of these cases, subjects with complete laboratory investigation (complete blood count - CBC, ferritin, total iron binding capacity - TIBC, and serum) and blastocystis hominis infection were included in this study as the case group. Of these cases, 6851 cases had only B. hominis infection. In the control group, 3615 subjects without parasite infestation were included. Age, haemoglobin (Hb), serum iron, TIBC, white blood cell (WBC), platelet (PLT), mean corpuscular volume (MCV), haematocrit (HCT) and erythrocyte sedimentation rate (ESR) were recorded for cases and controls. SPSS software version 13.0 was used for analysis. Independent sample t-test and χ(2) tests were used for comparison. RESULTS: Erythrocyte sedimentation rate level was significantly higher in cases with B. hominis infection (p < 0.05). C-reactive protein level was positive in 1.46% of cases and 0.5% of controls, which was statistically significant (p < 0.05). Frequency of serum iron < 120 was significantly higher in cases with B. hominis infection compared to controls. Occult blood was positive in 0.93% of cases and in none of the controls (p < 0.05). CONCLUSIONS: The ESR, CRP and occult blood was significantly higher in cases with B. hominis infection.

Incremental diagnostic value of circulating pentraxin in patients with intermediate risk of coronary artery disease.

OBJECTIVES: Pentraxins are a superfamily of multifunctional conserved proteins, some of which are components of the humoral arm of innate immunity and behave as functional ancestors of antibodies. They are divided into short (C reactive protein) and long pentraxins (pentraxin 3; PTX3). We investigated the diagnostic values of systematic arterial and coronary sinus (PTX3) in developing prediction models for estimating pretest probability of coronary artery disease (CAD) among an intermediate-risk population of patients with chronic stable angina. DESIGN: Cross-sectional analysis. SETTING: Referral cardiology hospital. PARTICIPANTS: Patients with chronic stable angina, without evidence of previous CAD if they were referred for angiography. MAIN OUTCOME MEASURES: All participants underwent diagnostic angiography. Prevalence rate ratio (PRR) of angiographically-determined coronary artery stenosis was separately examined in association with coronary sinus and femoral artery PTX3 concentrations using a general linear model. Duke treadmill score (DTS) was derived from the results of treadmill exercise cardiac stress testing. PTX3 data were collected in 100 patients with DTS-determined intermediate-risk chronic stable angina (aged 56.1 (1.1) years, 51 female). RESULTS: Both coronary sinus (PRR: 2.33, 95% CIs 1.64 to 3.31) and femoral artery PTX3 (PRR: 2.09, 95% CIs 1.46 to 2.97) independently predicted the prevalence rate of coronary artery involved with stenosis independent of the established CAD risk factors. Femoral artery PTX3 was highly correlated with coronary sinus PTX3 (ß=0.8, 95% CIs 0.66 to 0.94; p value<0.001). When we added femoral artery PTX3 to the predictive models incorporating traditional CAD risk factors, net reclassification improvement indices were 40% (cutpoint-free) and 15% (cutpoint-based). In the presence of PTX3, high-density lipoprotein cholesterol (HDL-C) was no longer protective against CAD. CONCLUSIONS: Gathering information on systemic arterial PTX3 may help more accurately reclassify DTS-determined patients with intermediate-risk chronic stable angina into more appropriate risk categories. PTX3 possibly, at least in part, mediates the protective effect on CAD of HDL-C.

Study of serological and clinical factors among juvenile rheumatoid arthritis cases admitted to Mofid Children's Hospital and Imam Hossein Hospital, Tehran, Iran.

INTRODUCTION AND AIM: Juvenile Rheumatoid Arthritis is the most common rheumatologic disease of childhood period. The aim of study was to compare ANA positive and ANA negative cases. PATIENTS AND METHODS: This observation study was performed as correlation research. All cases with diagnosis ofJRA who visited Mofid Children's Hospital and Imam Hossein Hospital were included in this study. Duration of this study was from 2006, 1 October till 2008, 31 October. All patients were examined carefully by an experienced pediatric rheumatologist. Age, sex, disease onset, age at diagnosis, RF, ANA, HLA-B27, ESR, type of disease, disease activity, and duration of inactivity were included in this study. ANA titer was measured by immunoflurocence technique. Patients were categorized according to sex, ANA, and type of disease and then group was compared with each other. Data was analyzed by SPSS Ver. 16 (Chicago, IL, USA). This study was approved by Ethical Committee of university. RESULTS: In this study, 61 cases were enrolled. Twenty five cases (41%) were males and 36 cases were females. Mean of age at disease onset was 6.1 +/- 3.1 (Range 6 months to 12.5 years). Mean of age at disease diagnosis was 6.7 +/- 3.2. Mean of age at time of study was 7.6 +/- 3.5 (1.4 to 14 years). From all cases, 38 cases were oligoarticular, 18 cases were polyarticular and 5 cases were systemic onset. From 61 cases, 22 (36.1%) cases, had ANA positive JRA. Of these cases, 14 cases were oligoarticular and 8 cases were polyarticular. CONCLUSION: Except for sex and morning stiffness, there is significant correlation between type of disease and ANA,RF,HLA-B27, response to treatment, early onset erosion, subcutaneous nodule, and uveitis (P < 0.05). There is significant correlation between sex and ANA, RF, HLA-B27, early erosion, response to treatment, subcutaneous treatment, and uveitis (P < 0.05). There is significant correlation between ANA seropositivity and HLA-B27, early erosion, response to treatment, uveitis and subcutaneous nodule. Our results showed that there is significant correlation among ANA and other factors except morning stiffness. Another prospective study is recommended.