Iranian Journal of Allergy, Asthma and Immunology
Volume:3 Issue: 2, Jun 2004

Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus that infects about 95% of the adult population. The majority of primary infections occurs in early childhood and is generally subclinical; it can cause infectious mononucleosis (IM), which is usually a self-limiting lymphoproliferative disorder. However, infection of EBV occasionally results in severe, often lethal diseases, which include fatal IM, hemophagocytic syndrome, polyclonal lymphoproliferative disorders, and malignant lymphoma. These severe EBV-related illnesses occur secondary to some primary immunodeficiency diseases showing inefficient immune reaction to EBV. One example is X-linked lymphoproliferative disease (XLP), which is caused by mutations in the SLAM-associated protein (SAP) gene. The major clinical manifestations of XLP are fulminant IM, malignant lymphoma and dysgammaglobulinemia. Aplastic anemia, virus-associated hemophagocytic syndrome, and vasculitis have also been reported in XLP. We have developed a flow cytometric method using the anti-SAP monoclonal antibody to search for XLP. This clinically useful assay has successfully been used to identify XLP patients in Japan. In this review, clinical and mutational characteristics of XLP in Japan are mainly described. In addition, it is shown that the similar situations to XLP can occur in other primary immunodeficiencies involving T-cell killing function, such as autoimmune lymphoproliferative syndrome caused by Fas gene mutations or familial hemophagocytic lymphohistiocytosis caused by perforin gene mutations. Finally, the EBV-related terrible disease condition, namely chronic active EBV infection, which is common in Asian areas but its genetic background remains to be elucidated, will be touched on.

Ataxia-Telangiectasia (AT) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, radiation sensitivity and cancer predisposition. The ATM gene on human chromosome 11q22.3 has recently been identified as the gene responsible for ataxia-telangiectasia (AT). The gene mutated in AT, which has been designated as the ATM gene, encodes a large protein kinase with a PI-3 kinase-related domain. More than 100 mutations are broadly distributed throughout the ATM gene. The large size of the ATM gene (66 exons spanning ~150kb of genomic DNA) together with the diversity and broad distribution of mutations in AT patients, greatly limits the utility of direct mutation screening as a diagnostic tool. In this study, 20 families with at least one affected child clinically suspected to have ataxia-telangiectasia were examined and their DNA was extracted and amplified with standard methods. Sequencing methods were used to detect the new point mutation. Four exons which were hot spots for point mutations in ATM gene were detected by PCR-SSCP or PCR-RFLP.

Studies have shown that patients who do not produce donor specific and / or panel reactive anti-HLA antibodies have a longer graft survival. The purpose of this study was to evaluate the posttransplant humoral immune response towards HLA-class I antigens and the measurement of the serum creatinine levels which are used in monitoring posttransplant function of kidney. Serum samples from 132 renal transplant recipients were screened for preformed anti-HLA class I panel reactive antibodies (PRA) by means of microlymphocytotoxicity assay. The results revealed the presence of PRA in 26 (19.7%) out of 132 transplanted patients. Graft function was evaluated by measurement of serum creatinine levels which revealed the mean of 1.75 mg/dl (SD: 1.08). Because of clinical significance of presence of different PRA amounts (>10%, > 20% and >50% of panel reactivity) in patients, correlation with kidney function status was analyzed. The obtained data highlighted a higher presence of serum creatinine levels in PRA-positive patients compared to negative patients (P<0.01). These results (and further studies for class II, …) can be used to implement new therapeutic strategies to curtail post transplant alloantibodies production and better

The aim of this work was to see whether tamarin immunisation with recombinant vaccinia virus expressing Epstein Barr Virus latent proteins could prime T cells which were, on activation, able to inhibit the outgrowth of Epstein Barr virus transformed cells in vitro. The vaccination appeared to be successful as all vaccinated tamarins developed vaccinia lesions. However, the vaccination protocol did not elicit a cell-mediated response capable of inhibiting the outgrowth of autologous Lymphoblastoid Cell Lines (LCLs) as seen in the tamarin infected with whole EBV, even though the recombinant vaccinia viruses used expressed the antigens commonly recognised by sero positive

Neutropenia is characterized by decrease in the absolute number of circulating neutrophils and an increase susceptibility to infections. The current study was performed in order to explain the clinical and laboratory findings of patients with antibody deficiency disorders associated neutropenia. The patients'' records of 19 neutropenic cases out of 207 patients with antibody deficiencies, who had been referred to Children''s Medical Center and enrolled in Iranian primary immunodeficiency registry, were reviewed. Nineteen cases (14 male and 5 female), with a mean age of 10.7±5.7 years, were associated with neutropenia (9.2%). The disorders with associated neutropenia were Hyper IgM syndromes (3 of 8), Common variable immunodeficiency (13 of 109), and X-linked agammaglobulinemia (3 of 45). The median age for the onset of disease and diagnosis age were 15 months (1-134) and 3.8 years (6 months-13 years), respectively. The most common infections during the course of illness were pneumonia (13 cases), diarrhea (12 cases), oral candidiasis (9 cases), otitis media (6 cases), sinusitis (6 cases), cutaneous infections (5 cases), and abscess (5 cases). Other less frequent infections were: conjunctivitis, oral ulcers, meningitis, and osteomyelitis. Three neutropenic patients died because of recurrent infections. Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.

Chronic Granulomatous Disease (CGD) represents a group of inherited disorders of phagocytic system, manifesting recurrent infections at different sites. The present study was accomplished in order to determine the gastrointestinal manifestations of CGD patients. Fifty-seven patients (38 males and 19 females) with CGD, who had been referred to three immunodeficiency referral centers in Iran, were studied during a 24-year period (1980-2004). The median age at the time of study was 14.5 years old (1-56 years). The median onset age of symptoms was 5 months (1 month – 13.75 years), and that of diagnostic age was 5 years (2 months- 54.1 years), with a diagnostic delay of 33 months, on average. Seven patients were presented with acute diarrhea, 3 with oral candidiasis, and 2 with liver abscesses as the first chief complaints. Twenty-four cases (42.1%) had been complicated by gastrointestinal manifestations during their course of the disease. Of those, 12 cases (21.1%) had diarrhea, 7 (12.3%) oral candidiasis, 5 (8.8%) hepatitis, 4 (7.0%) hepatic abscess, and 2 cases (3.5%) gastric outlet obstruction. Also, failure to thrive was detected in 6 patients (10.5%). Four patients died (7%). CGD should be excluded in any patient with gastrointestinal manifestations especially chronic diarrhea, hepatic abscess, and gastric outlet obstruction.

Asthma is one of the most common problems of childhood, responsible for a significant proportion of abstinence from school because of chronic illness. This study was carried out among the school-aged children (7-18 years) in Tehran schools during 2002-2003, in order to determine the frequency of asthma. According to the recommendation of WHO (World Health Organization), we designed a questionnaire, containing 8 standard questions, and the students were given necessary information to complete the questionnaires. The pre-high and high schools students completed the questionnaires but the parents of primary school students completed them on their behalf. The prevalence of asthma was 35.4% in Tehran; this prevalence was higher in the boys (37.1%), as compared to the girls (33.5%). The prevalence of this disease has been estimated about 39.5% in pre-high schools, 35.4% in high schools and 31.6% in primary students. Based on this survey, the most common clinical manifestations of asthma were: prolonged cough lasting more than 10 days (22.4%), and exercise induced wheezing or dyspnea (16.9%), followed by repeated dyspnea or wheezing (6.4%). The prevalence of asthma is high among the students of Tehran schools and it needs more careful screening programs along with additional information to the patients and parents about the disease.

We present the first reported case of antiphospholipid syndrome with stroke in an Iranian boy (7-month-old) who had two ischemic strokes within a period of 2 months. Serum anticardiolipid antibody was positive and the patient had low levels of protein S and C. This case emphasizes the importance of antiphospholipid antibody in children with unexplained ischemic strok