Defective Treg generation and increased type 3 immune response in leukocyte adhesion deficiency 1.

In 15 Turkish LAD-1 patients and controls, we assessed the impact of pathogenic ITGB2 mutations on Th17/Treg differentiation and functions, and innate lymphoid cell (ILC) subsets. The percentage of peripheral blood Treg cells, in vitro-generated induced Tregs differentiated from naive CD4+ T cells were decreased despite the elevated absolute counts of CD4+ cells in LAD-1 patients. Serum IL-23 levels were elevated in LAD-1 patients. Post-curdlan stimulation, LAD-1 patient-derived PBMCs produced more IL-17A. Additionally, the percentages of CD18-deficient Th17 cells expanded from total or naïve CD4+ T cells were higher. The blood ILC3 subset was significantly elevated in LAD-1. Finally, LAD-1 PBMCs showed defects in trans-well migration and proliferation and were more resistant to apoptosis. Defects in de novo generation of Tregs from CD18-deficient naïve T cells and elevated Th17s, and ILC3s in LAD-1 patients' peripheral blood suggest a type 3-skewed immunity and may contribute to LAD-1-associated autoimmune symptoms.

The plethora, clinical manifestations and treatment options of autoimmunity in patients with primary immunodeficiency.

AIM: Although the association between primary immunodeficiency and autoimmunity is already well-known, it has once again become a topic of debate with the discovery of newly-defined immunodeficiencies. Thus, investigation of the mechanisms of development of autoimmunity in primary immunodefficiency and new target-specific therapeutic options has come to the fore. In this study, we aimed to examine the clinical findings of autoimmunity, autoimmunity varieties, and treatment responses in patients who were genetically diagnosed as having primary immunodeficiency. MATERIAL AND METHODS: The files of patients with primary immunodeficiency who had clinical findings of autoimmunity, who were diagnosed genetically, and followed up in our clinic were investigated. The demographic and clinical features of the patients and their medical treatments were evaluated. RESULTS: Findings of autoimmunity were found in 30 patients whose genetic mutations were identified. The mean age at the time of the first symptoms was 8.96±14.64 months, and the mean age of receiving a genetic diagnosis was 82.55±84.71 months. The most common diseases showing findings of autoimmunity included immune dysregulation, polyendocrinopathy, enteropathy X-linked syndrome (16.7%); autoimmune lymphoproliferative syndrome (10%); lipopolysaccharide-responsive beige-like anchor protein deficiency (10%); and DiGeorge syndrome (10%). Twelve (40%) patients showed findings of autoimmunity at the time of first presentation. The most common findings of autoimmunity included inflammatory bowel disease, inflammatory bowel disease-like findings (n=14, 46.7%), immune thrombocytopenic purpura (n=11, 36.7%), and autoimmune hemolytic anemia (n=9, 30.0%). A response to immunosupressive agents was observed in 15 (50%) patients. Ten patients underwent hematopoietic stem cell transplantation. Six patients were lost to follow-up due to a variety of complications. CONCLUSION: Autoimmunity is frequently observed in patients with primary immunodeficiency. The possibility of primary immunodeficiency should be considered in patients with early-onset manifestations of autoimmunity, and these patients should be carefully monitored in terms of immunodeficiency development. Early diagnosis of primary immunodeficiency may provide favorable outcomes in terms of survival.

Potentially Beneficial Effect of Hydroxychloroquine in a Patient with a Novel Mutation in Protein Kinase Cδ Deficiency.

Protein kinase C delta (PRKCD) has essential functions in controlling B-cell proliferation and apoptosis, development of B-cell tolerance and NK-cell cytolitic activity. Human PRKCD deficiency was recently identified to be causative for an autoimmune lymphoproliferative syndrome like disorder with significant B-cell proliferation particularly of immature B cells. Here we report a child with a novel mutation in PRKCD gene who presented with CMV infection and an early onset SLE-like disorder which was successfully treated with hydroxychloroquine.

Experience of influenza A H1N1 in a paediatric emergency unit.

This study was carried out to evaluate symptoms, clinical findings, treatment options and complications of H1N1 influenza infection in patients who applied to our emergency unit during the influenza season in 2009. The clinical and laboratory findings of children with influenza A (H1N1) during the influenza season in 2009 were evaluated retrospectively. Influenza A was diagnosed by polymerase chain reaction and/or rapid antigen test. Clinical and laboratory findings of the patients with H1N1 (group I) and without H1N1 (group II) were compared. Fever and myalgia were noted to be higher in group I (p <0.05). The mean body temperature in group I was 39.0?, which was statistically different from group II (p <0.001). Myalgia was observed only in group I (15.4%), but not in group II (p <0.05). There were three patients with diarrhoea, two of whom were in group I, and they had no significant respiratory symptoms. Lymphopenia was seen in 18 patients (81.8%) in group I and in four patients (23.5%) in group II (p <0.05). Oseltamivir treatment was applied to 28 patients, where 24 had severe symptoms, nine had comorbid factors and two did not have any of these. The fever was higher in group I and myalgia was present only in group I. In group I, the lymphocyte count was significantly lower than in group II. The fever was higher in patients of H1N1 (average of 39°C) and myalgia was present only in patients with H1N1. The lymphocyte count was significantly lower in patients with H1N1 than those without H1N1. While none of the patients required intensive care, three patients requiring hospitalization were discharged after referral and completion of their treatment.

[Relationship between migraine-type headache in childhood with cow's milk allergy and egg-white allergy]. / Çocukluk çaginda migren tipi basagrisi ile inek sütü ve yumurta aki allerjisi arasindaki iliski.

OBJECTIVES: Migraine is a very common headache disorder. Due to the co-occurrence of migraine and allergic disorders, allergic mechanisms have been thought to play a role in migraine pathophysiology. This study aimed to investigate the association between cow's milk allergy and egg-white allergy and migraine-type headache of childhood. METHODS: We included 39 children with migraine-type headache and 167 children with no headache who had been evaluated previously in a school screening study program. Egg-white and cow's milk-specific IgE levels were measured for all involved subjects. RESULTS: Specific IgE levels were positive for cow's milk in 4 children and for egg-white in 2 children, respectively. No meaningful relationship was detected between food allergies and migraine. However, specific IgE levels for egg-white were significantly higher in migraineurs (p=0.008). CONCLUSION: Childhood migraine does not appear to be associated with cow's milk or egg-white allergy. However, the elevation of egg-white-specific IgE levels in migraine-type headache may signify the possible presence of shared pathogenetic pathways in the development of migraine and food allergies.