Phenotyping and long-term follow up of patients with hyper IgE syndrome.

INTRODUCTION AND OBJECTIVES: Long-term follow up of patients with hyper IgE syndrome (HIES), as a primary immunodeficiency disorder, has been poorly investigated. This study describes common clinical and immunological features of patients with HIES in the last 10 years in Shiraz University of Medical Sciences, Shiraz, Iran. METHODS AND PATIENTS: In this cross-sectional study, the symptoms and medical records of 18 patients, who were diagnosed with HIES, were observed. Genetic and immunologic study was also performed. RESULTS: Eighteen patients with the mean age of 13 years old were investigated. Ten patients were detected to have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES). So, 14 patients with known genetic results were considered for further data analysis. Food allergy, eczema, viral and skin infections were the major complications of AR-HIES patients. The major clinical complications of AD-HIES patients were pneumonia, skin infections and eczema. Food allergy and viral infection were significantly higher in DOCK8 deficient patients. The most common causes of hospitalization in both AR-HIES and AD-HIES patients were pneumonia, skin infections and sepsis. The most common cause of death was found to be sepsis. CONCLUSIONS: AD-HIES and AR-HIES cannot be differentiated only based on the clinical presentations. Genetic features are also necessary for better diagnosis. This study, summarizing the clinical, immunological and genetic information of the patients with AD-HIES and AR-HIES, may open a way for better diagnosis and management of HIES.

Novel AICDA mutation in a case of autosomal recessive hyper-IgM syndrome, growth hormone deficiency and autoimmunity.

BACKGROUND: The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders, which have been rarely reported to be associated with growth hormone deficiency (GHD). METHODS AND RESULTS: A nine-year-old girl with recurrent urinary tract infections, diarrhoea, sinopulmonary infections, and failure to thrive since the age of six months had normal CD3+, CD4+, CD8+T lymphocytes, and CD19+B lymphocytes and natural killer (NK) cells, but extremely elevated IgM and significantly decreased IgG and IgA. In view of the patient's short stature, growth hormone evaluation was carried out and growth hormone deficiency established. The patient underwent Ig replacement therapy and received growth hormone therapy in addition to antibiotics and responded well. Furthermore, the patient developed benign cervical lymphadenopathy, as well as elevated erythrocyte sedimentation rate, positive autoantibodies to SSA-Ro, and severely dry eyes, which partially responded to both the punctate occlusion and systemic corticosteroids, at the age of seven years. Sequencing analysis of the exons from activation-induced cytidine deaminase (AICDA) gene revealed that the patient was homozygous for a single T to C transversion at position 455 in exon 4, which replaces a Valine with an Alanine. CONCLUSIONS: To our knowledge, this is a new AICDA mutation, which has not been reported previously in HIGM. The mutation analysis could improve diagnosis of HIGM patients and also elaborating on the spectrum of AICDA mutations.

Bcgitis and vaccine-derived poliovirus infection in a patient with a novel deletion in RAG1 binding site.

A girl who developed severe BCGitis and vaccine-derived poliovirus infection was discovered to have a novel deletion of RAG1. A neonatal screening program for SCID would identify affected infants at birth, before live vaccines are administered.

Isolated growth hormone deficiency in a patient with immunoglobulin class switch recombination deficiency.

Growth hormone deficiency (GHD) may be associated with a number of immunodeficiency diseases, but its association with immunoglobulin class switch recombination (Ig CSR) deficiencies is very rare. We report the case of a patient with a history of recurrent diarrhea and respiratory infections diagnosed with hyper IgM syndrome on the basis of immunological findings (low serum levels of IgG and IgA and an elevated serum level of IgM). In view of the patient's short stature, growth hormone evaluation was performed and growth hormone deficiency confirmed. The patient received growth hormone therapy in addition to Ig replacement therapy and antibiotics and responded well. As the coding regions of the genes known to be responsible for Ig CSR (CD40L, CD40, AICDA, and UNG) were intact in our patient, this might be a new form of Ig CSR deficiency.

Antiphospholipid antibodies and hepatitis C virus infection in Iranian thalassemia major patients.

Although the precise nature of Antiphospholipid antibodies is still not clearly defined, they are known to have association with thromboembolic events and have been found in hepatitis C virus (HCV) infection. Moreover, high prevalence of HCV infection and thrombotic risk is described in thalassemia. We aimed at investigating the prevalence of anticardiolipin antibodies (aCLAbs), lupus anticoagulant (LA), and their relation with HCV infection in Iranian thalassemic patients. Presence of anti-HCV antibody, serum HCV-RNA, aCLAbs, and LA activity was determined in 131 patients with thalassemia major (male/female: 63/68 aged 3-29 years) registered at thalassemia unit, Dastgheib Hospital, Shiraz, Iran. Sixty-one healthy controls were also included. Anti-HCV antibody was positive in 24 (18.3%), IgG aCLAbs in 56 (42.7%), and LA activity in 9 (6.9%) patients. 87.5% of patients positive for aCLAbs had a low titer of aCLAbs. Although none of the participants had a previous history of thrombosis, higher prevalence of aCLAbs was detected in thalassemic patients compared with controls. No significant difference in the prevalence of aCLAbs was found between HCV-infected and noninfected patients. A high prevalence of aCLAbs, the majority in low titers, was detected in Iranian thalassemic patients irrespective of previous history of thrombosis and presence of HCV infection.

RBC alloimmunization in blood transfusion-dependent beta-thalassemia patients in southern Iran.

beta-thalassemia is considered a severe, progressive anemia, which needs regular transfusions for life expectancy. One of the most important complications of regular blood transfusions may be alloimmunization, which increases the need for transfusion. This study was performed to investigate the production of red cell alloantibodies in beta-thalassemia patients in Shiraz, southern Iran. Blood sampling was performed among 711 beta-thalassemia patients in Dastgheib hospital in 2002-2004. Direct and indirect coombs tests were performed to check the auto and alloantibodies and a panel test was conducted to detect the type of alloantibodies. Auto and alloantibodies were observed among 1.7% and 5.3% of patients, respectively. The most common alloantibodies were Anti-kell (50%) > Anti-Rh (D) (15.8%) > Anti-Rh (E) (10.5%). All the patients who had developed alloantibody were in the age group of 6 years or more. So for decreasing the rate of alloantibody synthesis, we should crossmatched the packed cells for minor blood groups especially for kell and Rh(E) in addition to major blood groups from the start of transfusion.

Frequency and significance of immediate contact reactions to peanut in peanut-sensitive children.

BACKGROUND: Parents of atopic children frequently report, and are alarmed by, contact reactions to foods. Some schools restrict foods due to concerns regarding possible systemic reactions following contact in allergic children. OBJECTIVE: We aimed to determine the frequency with which peanut-sensitive children exhibited contact sensitivity to peanut butter and to assess the significance of such reactions. METHODS: One gram of peanut butter was applied directly to the skin of 281 children who were skin prick test (SPT) positive to peanut (immediate skin application food test; I-SAFT). The test was considered positive if one or more weals were present when the patch was removed after 15 min. A subset of children then underwent an open-label oral challenge with graded amounts of peanut protein. RESULTS: During 3515 clinic visits, 330 I-SAFT tests for peanut contact sensitivity were performed; 136 (41%) were positive. The mean SPT diameter was 10 mm in the I-SAFT-positive children and 8.5 mm in the I-SAFT-negative children (t-test, P<0.0001). No child had a systemic reaction following topical application of peanut butter. Eighty-four children had 85 oral challenges after blinded, placebo-controlled I-SAFT testing. Challenge was positive in 26/32 of those with a positive I-SAFT and negative in only 6/32. Challenge was also positive in 26/53 but negative in 27/53 of those with a negative I-SAFT (sensitivity 50%, specificity 82%, chi2, P=0.003). CONCLUSION: A minority of children sensitized to peanut (positive SPT) develop localized urticaria from prolonged skin contact with peanut butter. No tested subjects, including ones with systemic reactions upon oral challenge, developed a systemic reaction to prolonged skin exposure to peanut. Therefore, systemic reactions resulting from this mode of contact with peanut butter appear highly unlikely.