Iranian Journal of Allergy, Asthma and Immunology
Volume:14 Issue: 5, Oct 2015

Epstein-Barr virus (EBV) was discovered 50 years ago from an African Burkitt lymphoma cell line. EBV-associated lymphoproliferative disorders (LPDs) are life- threatening diseases, especially in children. In this article, we review EBV-associated LPDs, especially in the area of primary immunodeficiency disease (PID). We searched PubMed for publications with key words including EBV infection, lymphoma, LPDs and PID, and selected the manuscripts written in English that we judged to be relevant to the topic of this review. On the basis of the data in the literature, we grouped the EBV-associated LPDs into four categories: nonmalignant disease, malignant disease, acquired immunodeficiency disease and PID. Each category has its own risk factor for LPD development. EBV-associated LPD is a complex disease, creating new challenges for diagnosis and treatment.

The relationship between Mycoplasma pneumoniae (MP) infection and asthma has rarely been explored through examination of airway reactivity. The aim of this study was to determine airway reactivity changes after MP infection in children. First, 106 children were divided into four groups according to the existence of MP infection and/or asthma. Then children with only MP belonged to the MP group; children who had both MP infection and asthma belonged to the MP+A group; children with asthma but not MP infection belonged to the non-MP+A group; normal children were classified as normal control (NC) group. Each subject underwent a bronchial provocation test (BPT) after effectively controlling the symptoms. Airway hyperresponsiveness (AHR) parameters were compared among the groups. BPT positive rates were also calculated and compared. All AHR parameters decreased following MP infection, with a more significant decrease of small airway reactivity related indexes. The BPT-positive rate in the MP+A group was significantly higher than that in the MP group. Large airway reactivity showed no significant differences between the MP+A and non-MP+A groups, while the small airway reactivity augmented more significantly in the MP+A group. MP infection caused increased reactivity of both large and small airways in lungs, and BPT-positive identification in some patients.

Orchard workers in north China are highly exposed to orchard pollens, especially peach and other Rosaceae family pollens during pollination season. The aim of this study was to investigate whether occupational allergy to peach tree pollen as a member of Rosaceae family is IgE-mediated and to evaluate the cross-reactivity among Rosaceae family pollens. Allergen skin test and conjunctival challenge test were performed; enzyme linked immune-sorbent assay (ELISA), inhibiting ELISA, western immunoblotting and inhibiting western immunoblotting were done with Rosaceae family orchard pollens, including peach, apricot, cherry, apple and pear tree pollens. Mass spectrometry was also performed to probe the main allergen component and cross-reactive protein. Sensitizations to peach pollen were found in both skin test and conjunctival challenge in the patients. Serum specific IgE to three pollens (peach, apricot and cherry) were detected through ELISA. When peach pollen used as solid phase, ELISA inhibition revealed other four kinds of pollens capable of inducing partial to strong inhibitions (45% to 87%), with the strongest inhibition belonging to apricot pollen (87%). Western blotting showed predominant IgE binding to a 20 KD protein among these pollens, which appeared to be a cross-reactive allergen component through western blotting inhibition. It was recognized as a protein homologous to glutathione s-transferase 16 from Arabidopsis thaliana. Peach and other Rosaceae family tree pollen may serve as a potential cause of IgE mediated occupational respiratory disease in orchard workers in north China.

To clarify the effect of γδ T cells and invariant Natural Killer T (iNKT) cells in pathophysiology of dyspeptic disorders, number of these two cells in patients with non-ulcer dyspepsia (NUD), peptic ulcer disease (PUD), and gastric cancer (GC) were compared. Patients with dyspepsia were divided into three groups of NUD, PUD, and GC according to their endoscopic and histopathological examinations. Helicobacter pylori infection was diagnosed by rapid urease test and histopathology. The number of peripheral blood CD3+TCRgd+ T cells and CD3+Va24Ja18+ iNKT cells were determined by flow cytometry. Immunohistochemistry (IHC) was also used for identifying the TCRgd+ cells. Forty two patients with NUD (31.6%), 44 with PUD (33.1%), and 47 with GC (35.3%) were included in the study. The frequency of CD3+TCRgd+T cells in peripheral blood of patients with GC (2.71±0.25) was significantly lower than that in NUD (3.97±0.32, p<0.05) and PUD groups (3.87±0.32, p<0.05). However, there was no significant difference in CD3+TCRgd+T cell percentage between the NUD and PUD groups. The frequency of TCRgd+ lymphocytes was significantly lower in tissue samples from patients with GC (4.81±0.53) than in NUD (11.09±1.09, p<0.0001) and PUD groups (11.11±1.01, p<0.0001). Also, we could not find any significant difference in the percentage of mucosal TCRgd+ cells between the NUD and PUD groups. The results showed no significant difference in iNKT cells percentage among the three groups of patients. The results suggest that decreasing number of γδ T cells may be related to development and progression of gastric cancer.

The B-cell CD20 antigen is one of the most reliable surface targets in immunotherapy of B lymphoma. In this project, we studied the production and characterization of a new monoclonal antibody against chimeric human CD20 extra loops (hCD20 exl). The results showed that clone C12H, IgG2/k isotype reacted with the antigen in ELISA and immunoblot. The Kd value was found to be 2×10-9M and flow cytometry results showed that 99.9% and 99.7% of the Daudi and Raji cells respectively were stained with C12H monoclonal antibody (mab) but not with Jurkat cell lines. It also effectively competed with Rituximab, thus, the staining of the Daudi and Raji cell lines was reduced to 55.9% and 40.5% of cells respectively. Based on the high affinity reaction of C12H mab and appropriate reactivity of C12H mab with the native antigen on the surface of Raji and Daudi cells in flow cytometry, it was concluded that development and evaluation of C12H mab could be a beneficial candidate for further application in genetically engineered monoclonal antibody.

Inflammation is an important reaction underlying lumbar disc herniation (LDH). Th17 cells play a critical role in immune activation. Interleukin (IL)-21 controls the functional activity of effector T-helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. It plays important roles in chronic inflammation and autoimmune diseases. However, little is known about relationship between IL-21 and LDH. This study was aimed to determine the association between IL-21 levels and pain scores in LDH patients compared to healthy controls. We enrolled 34 LDH patients and 20 healthy controls in this study. The LDH patients underwent surgery. Pain intensity was recorded using visual analogue scale (VAS) scores preoperatively. Serum IL-21 and IL-17 levels in the peripheral blood were determined using enzyme-linked immunosorbent assay. Disc tissue was examined using western blot and quantitative reverse-transcription polymerase chain reaction to determine IL-21, IL-17, and cyclooxygenase (COX)-2 expression, and using immunohistochemistry to assess IL-21 expression. LDH patients exhibited significantly higher levels of serum IL-21 and IL-17 than healthy controls. Moreover, higher expression of IL-21, IL-17, and COX-2 was found in the protein and mRNA levels in disc tissues from LDH patients than in normal disc tissues. Different parameters like VAS pain scores, IL-17, and COX-2 were positively correlated with the IL- 21 levels. Enhanced production of IL-21 in disc tissues of LDH patients was also confirmed using immunohistochemical analyses. We concluded that inflammation was responsible for the pain associated with LDH, and that increased IL-21 expression may be associated with the pathogenesis of LDH.

Tetanus is caused by the tetanus neurotoxin (TeNT), a 150 kDa single polypeptide molecule which is cleaved into active two-chain molecules composed of a 50 kDa N-terminal light (L) and a 100 kDa C-terminal heavy (H) chains. Fragment C is further subdivided into two subdomains: the proximal HCN subdomain and the extreme carboxy subdomain, HCC. HCC is considered as an immunodominant part of TeNT and is responsible for TeNT binding activity to neurons. In the present study, we investigated the ability of recombinant HCC(r HCC) to induce T cell activation. Our results showed that recombinant HCC has a stimulatory effect on IFN-γ secretion by T cells after 48h co-incubation in the presence of anti-TLR-2 Ab. Also, Hcc can induce the expression of CD69 on T cells. Our finding indicated that stimulatory effects of HCC on T cells are TLR-2 independent and anti-TLR-2 inhibitory antibody fails to neutralize HCC stimulatory effects on T cells. Furthermore, HCC is critical for immunogenic activity of TeNT and is able to induce T cells through TLR-2 independent pathway.

The object of this cross sectional study was to determine the HCV subtype 3a envelope protein binding affinity with Human Leukocyte Antigen. Envelope 1 (E1) protein is one of the structural proteins responsible for entering the cells through the receptors. The binding affinity of E1 protein epitopes to the selected Human Leukocyte Antigen (HLA) class I alleles was investigated using the computer-based tools. These prediction tools were also used to design the synthetic vaccine’s candidate epitopes and to identify the individuals/populations who are likely to be responder to those vaccines. The mean frequency of HLA I antigens in Pakistani population was calculated. Three alleles each from HLA A and B were selected. E1 protein sequence extracted from HCV 3a isolates was retrieved and twenty-four sequences of it were selected. NetMHCcons 1.0 server was used to determine the binding affinities of HLA alleles to the epitope sequences of 10 amino acids in length. A02, A03, A11, A24, A33, B08, B13, B15, B35 and B40 were the first five antigens more prevalent in Pakistan each from HLA A and HLA B.. We did not find any binding affinity between HLA A*201, B*1501 and B*4001 and epitopes from E1 sequences in a threshold of 50 nM. Totally five various epitopes derived from different isolates were characterized. The prediction of HLA-E1 epitope specific bindings and the forthcoming response can be a useful bioinformatics tool to uncover the right synthetic peptides for vaccine design purposes.

HLA-G is a tolerogenic molecule that expresses in cytotrophoblast cells and plays an important role in immune response suppression in maternal decidua. Interactions between the extracellular domains of the HLA-G protein with cell receptors of the immune system are well-known. This study investigated the association between HLA-G gene polymorphism with repeated implantation failure (RIF). We used PCR followed by the sequencing technique for exons 2, 3, and 4, as well as intron 2 of the HLA-G gene in 100 couples with histories of two or more failed assisted reproductive technique (ART) attempts. The data were compared with the results of our previous study. The results indicated that some alleles of the HLA-G gene such as: 0106, 010106, 01010106 and 0105N (null) alleles were significantly higher in the patient group compared to the control group (p<0.05). There were higher SNPs at the +482 T/C and +506 -/C positions in failed ART couples compared to controls (p=0.03; p=0.01, respectively). HLA-G gene polymorphisms do not clearly affect the risk for implantation failure in most couples who undergo ART. However allelic variations, particularly in exons 3 and 4, and intron 2 of the HLA-G gene can lead to ART failure in human embryos.

The clinical behavior of asthma varies with age at onset. This study was undertaken to identify associated markers of adult-onset allergic asthma (age ≥20 years).This cross-sectional study compared two groups: 58 patients with asthma onset at <20 years and 66 with onset at ≥20 years. They were compared depending on results of clinical history, and body mass index (BMI), aeroallergen sensitization, total serum IgE, eosinophil count, asthma control test, and asthma severity level. Ages at first asthma episode were 10.0 ± 6.6 and 33.4 ± 10.5 (p <0.001) in the <20 and ≥20 group, respectively. BMI was higher in adult asthmatic subjects (29.8 versus 27.1, P= 0.017), but BMI ≥30 kg/m2 was not associated with asthma onset in ≥20 years (odds ratio [OR] = 1.56, 95% confidence interval [CI] 0.759 to 3.211; p= 0.227). After multivariate analysis, allergic rhinitis and IgE ≥150 IU/mL were negatively correlated with asthma onset in ≥20 years old (OR adjusted [ORa] = 0.255, 95% CI 0.078 to 0.837, P= 0.024, and ORa =0.385, 95% CI 0.175 to 0.849, p= 0.018, respectively). Adult-onset allergic asthma was not different from early-onset asthma.