Expression of activation-induced cytidine deaminase gene in B lymphocytes of patients with common variable immunodeficiency

Common variable immunodeficiency [CVID] is a heterogeneous disorder characterized by reduced serum level of IgG, IgA or IgM and recurrent bacterial infections. Class switch recombination [CSR] as a critical process in immunoglobulin production is defective in a group of CVID patients. Activation-induced cytidine deaminase [AID] protein is an important molecule involving CSR process. The aim of this study was to investigate the AID gene mRNA production in a group of CVID patients indicating possible role of this molecule in this disorder. Peripheral blood mononuclear cells [PBMC] of 29 CVID patients and 21 healthy controls were isolated and stimulated by CD40L and IL-4 to induce AID gene expression. After 5 days AID gene mRNA production was investigated by real time polymerase chain reaction. AID gene was expressed in all of the studied patients. However the mean density of extracted AID mRNA showed higher level in CVID patients [230.95 +/- 103.04 ng/ml] rather than controls [210.00 +/- 44.72 ng/ml; P=0.5]. CVID cases with lower level of AID had decreased total level of IgE [P=0.04] and stimulated IgE production [P=0.02]; while cases with increased level of AID presented higher level of IgA [P=0.04] and numbers of B cells [P=0.02] and autoimmune disease [P=0.02]. Different levels of AID gene expression may have important roles in dysregulation of immune system and final clinical presentation in CVID patients. Therefore investigating the expression of AID gene can help in classifying CVID patients

study of AID gene expression in B lymphocytes from CVID patients

Common variable immunodeficiency [CVID] is one of the most frequent cases of primary immunodeficiency, it is likely that this heterogeneous disease is caused by several distinct genetic disorders. The activation-induced cytidine deaminase [AID] enzyme is involved in class switching, somatic hypermutation [SHM] and processes associated with gene conversion in the germinal center. In order to clarify the possible role of AID in the pathogenesis of CVID, we have studied the AID gene expression in CVID patients. Peripheral blood mononuclear cells [PBMC] from 21 patients and healthy controls were isolated. The isolated cells were stimulated by CD40L and IL-4 to induce AID gene expression. After five days, total RNA from the stimulated cells was extracted and AID gene expression was investigated by RT-PCR. RT-PCR results showed that after stimulation by CD-40L and IL-4, the AID gene was expressed in A/L of the samples. The control samples were also positive for AID gene mRNA expression. In this investigation we studied the expression of AID gene in CVID patients' B lymphocytes for the first time. Regards to our results which showed that all patients normally expressed the AID gene mRNA and considering that one of the main problems in a number of CVID patients is disorders in phenomena related to the germinal center and complete differentiation of B lymphocytes, it can be concluded that possible defects in other molecules involved in class switching is responsible for this disease. Understanding the various genetic defects responsible for this heterogeneous disease could lead to its division into more homogenous subtypes with distinct therapeutic strategies, so further investigations is recommended

Giant aneurysm of thoracic and proximal abdominal aorta in a patient with common variable immunodeficiency

Common variable immunodeficiency [CVID] is the most common symptomatic primary immunodeficiency disease, predisposing the patients to various tissue involvement and organ damage. Here a 16-year-old boy is presented who was referred to our center with cough, dyspnea, cyanosis, and history of recurrent pneumonia. The diagnosis of CVID was made according to reduction all serum immunoglobulin levels, normal numbers of T, B and NK lymphocyte subpopulations, poor antibodies responses. Considering abnormality in heart examination and chest X-ray, echocardiography and computed tomography angiography were performed which showed large thoraco-abdominal; aortic aneurysm in this patient. Although there are some reports of cardiovascular disease associated with primary antibody deficiencies, this is the first time that such large thoraco-abdominal aortic aneurysm is reported in CVID. This may be secondary to recurrent pulmonary infections or an unknown mutation process. Cardiovascular abnormalities are an entity that should be kept in mind in patients with primary immunodeficiency diseases