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Background: Data concerning impact of COVID-19 on children with rheumatic disorders in developing countries are limited. Methods: We conducted a retrospective analysis, examining the medical records of 49 children (15 males, 34 females) with rheumatologic disorders who got infected with SARS-CoV2. They were recruited, over a period of 17 months, from the Children’s Hospitals of Ain Shams, Mansoura and Assiut Universities in Egypt. Data recorded were the type and duration of rheumatologic, antirheumatic treatment received, and COVID-19 presentation including severity, and outcome. Complete blood count (CBC), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), lactate dehydrogenase enzyme (LDH), serum ferritin, and Ddimer levels were recorded. Results: Our series included 25 SLE, 16 JIA, two polyarteritis nodosa, two dermatomyositis, two mixed connective tissue disease, one systemic sclerosis, and one HSP patients. They had median (IQR) age of 13 (10-14) years. Twenty-nine (59.2%) patients had active disease flare. Fortyone (83.7%) patients were on corticosteroids, and 35 (71.4%) were on add-on immunosuppressives. Twenty-nine patients were hospitalized with median (IQR) admission duration of 25 (14-38) days. They included 8 mild/asymptomatic, 4 moderate, 6 severe, and 11 critical COVID-19 cases. Seven cases with critical COVID-19 passed away with mortality rate of 14.3 %. The deceased cases had higher neutrophil/lymphocyte ratio (p=0.003), higher CRP levels (p= 0.041) and higher D-dimer (p=0.001) and ferritin levels (0.002) as compared to survivors. Conclusion: Although reported to be milder in children, COVID-19 seems to have higher mortality among children with rheumatic disorders compared to rates reported in the general population. We could not find evidence for the impact of immunosuppressive treatment on COVID-19 related mortality, yet our findings need to be validated by wider scale prospective studies.

Background: Systemic lupus erythematosus (SLE) is a chronic multi-organ systemic autoimmune disease. Interleukin-17 (IL-17) is a powerful proinflammatory cytokine that is involved in the development of several autoimmune diseases, including SLE. Objective: We aimed to evaluate the serum IL-17 expression in pediatric SLE and correlate this to the disease activity and other biomarkers of disease activity . Methods: Thirty-six patients diagnosed with pediatric SLE were enrolled in the study and were classified according to the SLE disease activity index (SLEDAI) score into two subgroups; mild activity (SLEDAI

Predisposition to mycobacterial infection is a key presenting feature of several rare inborn errors of intrinsic and innate immunity. Hematopoietic stem cell transplantation (HSCT) can be curative for such conditions, but published reports are few. We present a retrospective survey of the outcome of 11 affected patients (7 males, 4 females) who underwent HSCT between 2007 and 2019. Eight patients had disseminated mycobacterial infection prior to transplant. Median age at first transplant was 48 months (9 -192); three patients were successfully re-transplanted due to secondary graft failure. Donors were matched family (1), matched unrelated (3), and mismatched unrelated and haploidentical family (5 each). Stem cell source was peripheral blood (9), bone marrow (4), and cord blood (1). TCRαβ/CD19 + depletion was performed in 6. Conditioning regimens were treosulfan, fludarabine (4), with additional thiotepa (in 8), and fludarabine, melphalan (2); all had serotherapy with alemtuzumab (8) or anti T-lymphocyte globulin (6). Median hospital stay was 113 days (36–330). Three patients developed acute grade I-II skin and one grade IV skin graft versus host disease. Four patients had immune-reconstitution syndrome. Two reactivated cytomegalovirus (CMV), 1 Epstein-Barr virus, and 3 adenovirus post HSCT. Nine are alive, 1 died early post-transplant from CMV, and the other was a late death from pneumococcal sepsis. Patients with active mycobacterial infection at HSCT continued anti-mycobacterial therapy for almost 12 months. In conclusion, HSCT is a successful treatment for patients with mycobacterial susceptibility even with disseminated mycobacterial infection and in the absence of an HLA matched donor.

BACKGROUND: Growing evidences highlight the role of the innate immune response in the pathogenesis of type 1 diabetes (T1D) vascular complications. Neutrophil lymphocytic ratio (NLR) and platelet lymphocytic ratio (PLR) are inexpensive but novel markers of chronic inflammation might have prognostic value in children with T1D. AIM: To study NLR and PLR levels in children with T1D in comparison to matched controls and correlate them with fraction-C of glycosylated hemoglobin (HbA1C) and micro-vascular complications. METHODOLOGY: Hundred children with T1D were compared to 100 matched healthy controls. History included diabetes duration, insulin dose and frequency of hypoglycemic attacks. Fundus examination and the simple rapid neuropathy disability score were done. HbA1C, fasting lipids, urinary albumin excretion and complete blood count were measured with assessment of NLR and PLR RESULTS: NLR was significantly higher (p = 0.008) and PLR was significantly lower (p = 0.007) in children with T1D than controls. NLR was positively correlated while PLR was negatively correlated with HbA1C, diabetes duration, fasting cholesterol, triglycerides and LDL. NLR was significantly higher (p

Background Systemic lupus Erythematous (SLE) is an autoimmune inflammatory disease characterized by antibodies directed against self-antigens, resulting in multi-organ damage. Up to 20% of cases are diagnosed during childhood with 55% of these patients are expected to develop lupus nephritis (LN). Objective At comparing the efficacy of mycophenolate mofetil versus pulse intravenous cyclophosphamide in induction of remission in pediatric patients with lupus nephritis. Subjects and Methods This is a retrospective study that was conducted in Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain-Shams University from the period of December 2007 to January 2017 on 65 pediatric patients with lupus nephritis taking either cyclophosphamide or Mycophenolate Mofetil as an induction therapy. Patients’ data was gathered from their medical records in the Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain-Shams University. Patients enrolled in the study after consideration of inclusion and exclusion criteria. Results Our studied patients were 65 patients divided into 58(89%) female and 7(11%) male with female: male ratio (8: 1) and their age ranged between (5- 18) years. There was no statistically significant difference between different laboratory parmaters used to compare between both groups (C3, 24 hour urinary protein, anti-DNA). However, the rate of change in SLEADI score was higher in patient receiving Cyclophosphamide and Mycophenolate mofetil, but with no significant difference. Conclusions No significant difference between group taking cyclophosphamide and mycophenolate mofetil.

Background The Ketogenic Diet (KD) is a high-fat, low-carbohydrate, and adequate-protein diet and a well-established treatment option for drug resistant childhood epilepsies. Neutrophils are important component of humans` innate phagocytic defense which usually arrive first at sites of infection and/or inflammation. Objectives The objective of this study was to assess the effect of ketosis induced by KD on neutrophils count. Methods This case control study was done in the Ketoclinic, Children’s Hospital, Ain Shams University, during the period of May 2018 till December 2019. It included 21 patients and 9 age and sex matched healthy children as a control group. Neutrophil counts were measured in both patients and controls both initially and after 6 months of KD usage. Results Although three patients reported increased incidence of infection after commencement of KD, the current study showed no significant change in the neutrophil count in studied patients compared to the controls after 6 months of KD. Conclusion KD has no effect on neutrophil number, however, further detailed studies for the full immunological profile including their function is needed to ensure that patients receiving this line of therapeutic nutrition aren`t susceptible to increased risk of infections.

Background Intravenous immunoglobulin G (IVIG) has been used as an antibody replacement therapy in primary immunodeficiency (PID) for more than 50 years. Most routinely, IVIG is used in patients with predominantly antibody deficiency such as: X-linked Agammaglobulinemia, common variable immunodeficiency and combined immunodeficiency such as: severe combined immunodeficiency. Aim To evaluate the efficacy and safety of regular IVIG therapy among patients with predominantly antibody deficiency in terms of frequency of infection and adverse effects. Methods Thirty patients diagnosed with predominantly antibody deficiency were recruited from the Pediatric Allergy and Immunology Unit, Children’s Hospital, Ain Shams University. These patients were followed up for one year in order to evaluate the frequency of infection and and adverse reactions of regular monthly IVIG therapy. The adequacy of IVIG dose was evaluated by the trough level of serum immunoglobulin G (IgG). Results Of the 30 patients, 21 (70%) were males and 9 (30%) were females. They had a median age of 87 months (range:15-294). Their median age at presentation and at diagnosis were 36 months (range :3-168) and 87 months (range:15-204) respectively. The mean ± SD of serum IgG before commencement of IVIG and after were 265.10 ± 108.39mg/dl and 572.04 ± 186.72 respectively. The rate of major infection dropped after starting replacement therapy with a median of 2 (1-2) before and 0 (0-1) after treatment. In spite of the reduction in the rate of pneumonia occurrence in patients with IgG trough level >500 mg/dl, it had no statistical significance. This could be attributable to small sample size. One patient developed anaphylaxis and was shifted to another brand. Conclusion IVIG is a safe and effective drug for patients with predominantly antibody deficiency. Compliance, adherence to therapy and appropriate dosage is needed to achieve better infection control.

Background Hydroxychloroquine (HCQ) is used in the management of a variety of autoimmune disorders, with well-established role in dermatology and rheumatology. However, Hydroxychloroquine and chloroquine (CQ) have been associated with irreversible visual loss due to retinal toxicity. Aim of the Work screening for field affection resulting from HCQ therapy in patients with SLE and assessing the diagnostic accuracy of the investigational methods employed. Subjects and Methods This is a cross-sectional controlled study that was carried out on 90 subjects ( Results In comparison to the normal field in the control group, 13 out of 45 (29%) of the patients treated with HCQ had visual field defects most commonly in the central/paracentral area in-spite of no complaint. Conclusion HCQ can affect the visual field and this was not related to the cumulative dose of the drug. Regular field assessment should be done for patients on regular HCQ treatment.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder of motile cilia dysfunction generally inherited as an autosomal recessive disease. Genetic testing is increasingly considered an early step in the PCD diagnostic workflow. We used targeted panel next-generation sequencing (NGS) for genetic screening of 33 Egyptian families with clinically highly suspected PCD. All variants prioritized were Sanger confirmed in the affected individuals and correctly segregated within the family. Targeted NGS yielded a high diagnostic output (70%) with biallelic mutations identified in known PCD genes. Mutations were identified in 13 genes overall, with CCDC40 and CCDC39 the most frequently mutated genes among Egyptian patients. Most identified mutations were predicted null effect variants (79%) and not reported before (85%). This study reveals that the genetic landscape of PCD among Egyptians is highly heterogeneous, indicating that a targeted NGS approach covering multiple genes will provide a superior diagnostic yield compared to Sanger sequencing for genetic diagnosis. The high diagnostic output achieved here highlights the potential of placing genetic testing early within the diagnostic workflow for PCD, in particular in developing countries where other diagnostic tests can be less available.

Background: Pediatric systemic lupus erythematosus (pSLE) accounts forabout 20% of all cases of Systemic Lupus Erythematosus (SLE), withnephritis occurring in approximately 50% of the patients. Objective: toevaluate the expression of CXCR3 in the kidneys and on CD4+ T cells inpSLE. Methods: This study was conducted on 45 patients with pSLEfollowing up at the Allergy and Immunology Clinic, Children’s Hospital, AinShams University and 45 age and sex matched healthy children as a controlgroup. Medical history, clinical examination and routine laboratoryinvestigations for assessment of disease activity were done for all patients,the frequency of CXCR3, CD4+ T cells was determined in all patients andcontrols. Twenty-five Paraffin blocks of patients with lupus nephritis (LN)(available at the time of the study) underwent immunohistochemistrystaining for the frequencies of Chemokine C receptor (CXCR3). Results:The absolute level and percentage of serum CD4+CXCR3+ weresignificantly lower among our patients as compared to healthy controls. Asignificant direct correlation was found between serum CD4+CXCR3+ andboth the lymphocytic count and quantitative Systemic Lupus erythematosusdisease activity index (SLEDAI), as well as a significant inverse correlationbetween it and 24 hours urinary proteins. Variable degrees of CXCR3expression seemed to have no impact on laboratory tests, British Isles LupusAssessment Group (BILAG) score and cumulative doses ofImmunosuppressives. Conclusion: Serum CD4+CXCR3+ and not renalCXCR3 may be a potential marker of LN activity.

No Abstract

Monogenic immune dysregulation diseases (MIDD) are caused by defective immunotolerance. This study was designed to increase knowledge on the prevalence and spectrum of MIDDs, genetic patterns, and outcomes in Middle East and North Africa (MENA). MIDD patients from 11 MENA countries (Iran, Turkey, Kuwait, Oman, Algeria, Egypt, United Arab Emirates, Tunisia, Jordan, Qatar, and Azerbaijan) were retrospectively evaluated. 343 MIDD patients (58% males and 42% female) at a median (IQR) age of 101 (42-192) months were enrolled. The most common defective genes were LRBA (23.9%), LYST (8.2%), and RAB27A (7.9%). The most prevalent initial and overall manifestations were infections (32.2% and 75.1%), autoimmunity (18.6% and 41%), and organomegaly (13.3% and 53.8%), respectively. Treatments included immunoglobulin replacement therapy (53%), hematopoietic stem cell transplantation (HSCT) (14.3%), immunosuppressives (36.7%), and surgery (3.5%). Twenty-nine (59.2%) patients survived HSCT. Along with infectious complications, autoimmunity and organomegaly may be the initial or predominant manifestations of MIDD., Alborz University of Medical Sciences, This work was supported by the vice chancellor for research, Alborz University of Medical Sciences.

This chapter briefly describes the universal intricacies caused by the COVID-19 pandemic, from the ineffectiveness of distance measures, the massive economic impacts, and the severe mental health challenges to the failure of finding a vaccine, a therapeutic agent or even accurately diagnosing the infection. The entire world is suffering, but every country is trying to combat this pandemic individually, and this deed is the main barrier that prevents reaching a peaceful end.

Ketogenic diet (KD) is one of the treatments in drug-resistant epilepsy (DRE). The current study aimed at assessing the effect of KD-induced ketosis on different immunological cells since ketosis is reported to affect neutrophil function. We recruited 21 pediatric patients diagnosed with DRE assigned to start KD. Anthropometric measurements, complete blood picture with differential count, phagocytic function, lymphocyte subsets, and IgG estimation were estimated initially and after 6 months of KD. There were no differences between the initial total leucocytic, neutrophil, and lymphocytic counts as well as the lymphocyte subsets, and the values after 6 months of KD. IgG values showed significant increase yet the values were still within the reference ranges. For the innate immune system, the phagocytic index was assessed and it showed a marked statistical reduction in patients after KD. KD has no effect on neutrophil and lymphocytic counts as well as the number of adaptive and immune cells; nevertheless, it causes a reduction in phagocytic index in DRE. Accordingly, further detailed study for the full immunological profile and function is needed to ensure the safety of this therapeutic line and correlate it with the clinical history.

Background: Obesity as a global public health problem is increasing in prevalence. Reports showed that obese children are more liable to infection than lean ones; it was claimed that obese subjects have altered peripheral blood total lymphocyte counts in addition to reduced lymphocyte proliferative response to mitogen stimulation as well as dysregulated cytokine expression. Objective: This study aimed to evaluate the effect of childhood obesity on cell mediated immunity as indicated by peripheral blood lymphocyte phenotyping. Methods: We enrolled 30 school-aged children (mean age 10±3.27 years). They comprised two groups; 20 obese children with a mean body mass index (BMI) of 39.2± 12.5 and 10 matched control subjects with mean BMI of 18.4± 1.9. They were subjected to detailed anthropometric evaluation including weight, height, and waist hip ratio in addition to calculation of BMI, complete blood counting, and flow cytometric assessment of T-helper (CD4), T-cytotoxic/suppressor (CD8), and natural killer (CD56) cell counts . Results : The absolute lymphocyte (CD3) and natural killer cell (CD56) counts were comparable in both groups. However, the CD4%, CD8%, CD4/CD8 ratio were significantly lower in the obese children ( p =0.02, 0.03, 0.015 respectively). A significant negative correlation could be elicited between the CD4 count and bodyweight, BMI, and hip waist ratio ( p = 0.00); the same was observed for CD4/CD8 ratio ( p = 0.00). On the contrary, CD8 correlated positively to the bodyweight, BMI, and waist hip ratio ( p = 0.00 for each) . Conclusion: Obesity has an impact on lymphocytic subset counts and further studies are needed to assess its effect on their function. Keywords: obesity, children immunology; CD markers; lymphocytes; BMI

Autoimmune lymphoproliferative syndrome (ALPS) is a rare immunodeficiency caused by mutations in genes affecting the extrinsic apoptotic pathway (FAS, FASL, CASP10). This study evaluated the clinical manifestations, laboratory findings, and molecular genetic results of 215 patients referred as possibly having ALPS. Double-negative T-cell (DNT) percentage and in vitro apoptosis functional tests were evaluated by fluorescence-activated cell sorting; interleukin 10 (IL-10) and IL-18 and soluble FAS ligand (sFASL) were measured by enzyme-linked immunosorbent assay. Genetic analysis was performed by next-generation sequencing. Clinical background data were collected from patients’ records. Patients were categorized into definite, suspected, or unlikely ALPS groups, and laboratory parameters were compared among these groups. Of 215 patients, 38 met the criteria for definite ALPS and 17 for suspected ALPS. The definite and suspected ALPS patient populations showed higher DNT percentages than unlikely ALPS and had higher rates of lymphoproliferation. Definite ALPS patients had a significantly more abnormal in vitro apoptosis function, with lower annexin, than patients with suspected ALPS (P = .002) and patients not meeting ALPS criteria (P < .001). The combination of elevated DNTs and an abnormal in vitro apoptosis functional test was the most useful in identifying all types of ALPS patients; the combination of an abnormal in vitro apoptosis functional test and elevated sFASLs was a predictive marker for ALPS-FAS group identification. Lymphoproliferation, apoptosis functional test, and DNTs are the most sensitive markers; elevated IL-10 and IL-18 are additional indicators for ALPS. The combination of elevated sFASLs and abnormal apoptosis function was the most valuable prognosticator for patients with FAS mutations.

Introduction Autoimmune lymphoproliferative syndrome (ALPS) is a rare autosomal immunodeficiency sometimes caused by mutations in 4 genes that affect the extrinsic apoptotic pathway (FAS, FASL, CASP10, CASP8). Objective This study evaluated patients’ clinical manifestations, laboratory findings and molecular genetic results in 250 patients with a preliminary diagnosis of ALPS. Methods Annexin expression levels and DNT rates were evaluated by FACs, and results were examined with the Shapiro-Wilk normality test. Normally distributed parameters were compared tested with parametric tests (One Way ANOVA), while abnormal distributions were compared and tested with non-parametric tests (Independent Samples Kruskal Wallis test). Results Of the 250 patients, 41 met the criteria for definitive ALPS, from which 14 had abnormal Annexin expression rates, 11 equivocal, and 10 normal. 22 of the 250 patients had suspected ALPS, of which only 1 had abnormal Annexin expression rates, 2 equivocal, and 17 normal. Definitive ALPS patients had a significantly lower annexin expression rate than both patients with suspected ALPS and patients not meeting the ALPS criteria (p=,003). The definitive ALPS patient population also showed higher double-negative T-cell levels than those with suspected ALPS or those with no clinical signs. The data shows that patients with FAS mutations are more likely to have low annexin levels than patients with CASP mutations. Regarding the sFASI, definitive ALPS patients showed higher values compared to patients with no ALPS or suspected ALPS (median sFASI: 186,4; median sFASI: 145,8pg/ml p=0,019; and median sFASI: 64,95pg/ml p=0,007 respectively). IL-10 levels also appeared to be higher in definitive ALPS patients. IL-18 showed no difference. Conclusions In conclusion, annexin levels are a useful marker for ALPS patients but only with FAS mutations. While DNT rate, IL-10 levels can confirm these results, our data show that IL-18 is a poor marker for ALPS.

Background: Lupus nephritis (LN) is more common and more severe is pediatric systemic lupus erythematosus (pSLE). Endothelial protein C receptor (EPCR) is an inducer of anti-apoptotic pathways in endothelial cells. Recent studies have taken elevated anti-injury biomarkers as EPCR into consideration regarding their roles to antagonize LN. Objectives: to evaluate the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in pediatric patients with LN. Methods: This study was conducted on 25 patients with pSLE following up at the Allergy and Immunology Clinic, Children’s Hospital, Ain Shams University. The 25 patients have LN proved by a previous renal biopsy. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients. Paraffin blocks of patients’ renal biopsies were subjected to immunohistochemistry staining for the frequency of mEPCR. Results: mEPCR was mainly expressed in the endothelium of the peritubular capillaries. Our results showed that an equal number of patients had nil and mild marker expression (8 patients each, 32%) while 9 patients (36%) showed moderate/strong marker expression. We found that 9 out of 10 (90%) of patients with class II had nil/mild marker expression, 5 patients out of 9 (55.5%) with class III had mild/moderate marker expression, while 5 patients 0ut of 6 (83.3%) with class IV and V had moderate/strong marker expression. We only found a significant statistical difference between the different degrees of mEPCR expression regarding 24 hours urinary proteins. No statistical significance was found between the different degrees of mEPCR expression and different immuno-suppressive therapy dose/kg or renal outcome using the renal British Isles Lupus Assessment Group (BILAG) score; in spite that most of the patients who got improved had nil/mild marker expression. Conclusion: mEPCR -bearing a statistically significant difference in relation to different LN classes- showed more expression in the more aggressive classes; a finding which might suggest a contribution of the endothelium of the renal parenchyma to the pathophysiology of more progressive LN. Hence the tissue marker might emerge as a potential new therapeutic target in the search for more selective treatment for SLE. Keywords: p SLE, mEPCR, renal biopsy, immunohistochemistry, BILAG, lupus nephritis

DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity, and allergy. The aim of this study was to assess the effect of different factors in the development of infections, autoimmunity, and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low immunoglobulin M levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3+, CD3+CD4+, and naïve CD4+CD45RA+CD27+ T lymphocytes compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T cells, as suggested by an accelerated decline of the naïve T lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4+ T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency.