Hyper IgE syndromes are groups of primary immunodeficiency diseases which present with a series of symptoms including recurrent infections accompanied by elevated serum IgE level and some atopic features. Both autosomal dominant and recessive mutations may cause hyper IgE syndrome. The autosomal dominant forms are mutations in signal transducer and activator of transcription3 (STAT3), ERBB2 and CARD11. The recessive forms are mutations in dedicator of cytokinesis8 (DOCK8) , phosphoglucomutase3 (PGM3) , thyrosin kinase2 (TYK2) and interleukin-6 ST. There are some features that help distinguish among different types of hyper IgE syndrome. In autosomal dominant form, connective tissue, skeletal and vascular abnormalities are prominent. In autosomal recessive form, viral infections, malignancies and neurological disorders are more prominent. The definite diagnosis is made by mutation analysis.

Background/objectives: CD40 ligand (CD40L) deficiency is an X-linked form of hyper Immunoglobulin M syndrome (XHIGM) that is caused by mutations of CD40Lgene. The aim of the present study was to investigate the clinical and molecular basis of this disorder in a group of Iranian patients with a long period of follow-up.
Methods: A total number of 21 patients diagnosed with X-HIGM, who were referred to and followed up at Children’s Medical Center (Pediatrics Center of Excellence affiliated to Tehran University of Medical Sciences, Tehran, Iran), were included in this retrospective cohort study. The medical and immunologic evaluations of patients were followed by mutation analysis to confirm the diagnosis.
Results: The median age of all participants was 7.50 (4.87-16.25) years. The median age at the time of disease onset was 8.00 (6.00-13.50) months. The majority of patients showed their first manifestation before 4 years of age. The median age of diagnosis was 23.00 (12.50-48.00) months, with a median diagnostic delay of 9.00 (1.50-28.00) months. Anemia was the most common hematologic manifestation, occurring in 71.4% of the patients. The median serum IgM concentration was 206 (82-335) mg/dL. Elevated IgM levels were observed in fifteen patients based on age-references and six patients had normal IgM levels. The mutation analysis among patients with the CD40L mutations revealed 15 missense, 5 frameshift-nonsense, and 1 splice-site mutation. Eight patients (38%) died during the study period. Respiratory infection such as pneumonia were the main cause of death in the 5 patients.
Conclusion: Earlier diagnosis of X-HIGM may provide effective management and lead to patients’ survival and better quality of life. Moreover, using whole-exome sequencing for detection of patients with HIGM phenotype is strongly recommended to differentiate it from intrinsic humoral immunity defects and to initiation the appropriate therapeutic procedures and management.

Background/objectives: Agammaglobulinemia is a primary immunodeficiency disorders (PID) which is identified by increased susceptibility to the bacterial infections, significant low antibodies and isohemagglutins and decreased peripheral B cells counts. Different clinical manifestations could be observed in these patients. Some of agammaglobulinemia patients manifest autoimmune disorders, while the association of autoimmunity and agammaglobulinemia is not clarified yet. In this study, we evaluated the frequency of autoimmunity in agammaglobulinemia patients and we compared their demographic, clinical and laboratory data in two groups of the patients with and without autoimmunity.
Methods: The present study included 147 patients diagnosed with agammaglobulinemia who were diagnosed at the Research Centre for Immunodeficiencies at the children’s medical Centre. A comprehensive history, demographic information, clinical manifestations, laboratory data were obtained from all patients to assess the autoimmune complications.
Results: Among 147 agammaglobulinemia patients, we identified 21 (14.2%) (18 males and 3 females) agammaglobulinemia patients who had autoimmune disorders. In a total of the patients, the most prominent clinical presentation was respiratory infections (72.4%). Among autoimmune disorders, Juvenile Rheumatoid Arthritis was the most important autoimmunity (38%) following Immune thrombocytopenia with the frequency of 14%.
Conclusion: Autoimmune diseases are not very common among agammaglobulinemia patients; however, these disorders should be considered as an important factor for management in the patients. Early diagnosis and suitable management of autoimmunity leads to enhancement of patient’s life quality in agammaglobulinemia cases.

Ataxia-telangiectasia is a rare primary immunodeficiency and multisystem DNA repair disorder which is caused by mutation in ataxia telangiectasia mutated (ATM) gene. The ATM protein plays a critical role in sensing DNA double-strand breaks (DSB), oxidative stress and other genetic stresses. The ATM can directly mention DNA ends in repair complexes and directly involved in the repair of DSBs induced during T cell and B cell rearrangement. Therefore, increase serum IgM level and recurrent infection mainly sinopulmonary, indistinguishable from hyper IgM syndrome can be a presentation of some AT patients. AT patients with class-switched defect are more prone to severe infections, autoimmunity and lymphoproliferative disorders. Herein we present an AT patient with characteristic feature of hyper IgM phenotype and lymphoproliferation is investigated.