Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138311120140301Islet Amyloid Polypeptide is not a Target Antigen for CD8+ T-Cells in Type 2 Diabetes11216760ENFathollahKalantarDepartment of ImmunologyMohammad HosseinDabbaghmaneshEndocrine and Metabolism Research Center, Shiraz University of Medical
Sciences, Shiraz, IranEmanuelaMartinuzziCochin Institute, Paris, FranceMohsenMoghadamiHIV/AIDS Research CenterZahraAmirghofranDepartment of ImmunologyAutoimmune
Disease Research CenterMedicinal and Natural Products Chemistry Research Center, Shiraz University
of Medical Sciences, Shiraz, Iran0000-0002-1027-7906Journal Article20160804<b>Background</b>: <span lang="JA">Type 2 diabetes (T2D) is a chronic metabolic disorder in which beta-cells</span> are destroyed. The islet amyloid polypeptide (IAPP) produced by beta-cells has been reported to influence beta-cell destruction. <span><br/><b>Objective</b>: </span><span lang="JA">To evaluate if IAPP can act as an</span> autoantigen and therefore, to see if CD8 <span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">+ </span></span><span lang="JA">T-cells specific for this protein might be</span> present in T2D patients. <span><br/><b>Methods</b>: </span><span lang="JA">Peripheral blood mononuclear cells (PBMC) were</span> obtained from human leukocyte antigen (HLA)-A2 <span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">+ </span></span><span lang="JA">T2D patients and non-diabetic</span> healthy subjects. Cells were then screened for peptide recognition using ELISPOT assay for the presence of IFN-γ producing CD8 <span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">+ </span></span><span lang="JA">T-cells against two HLA Class I-restricted</span> epitopes derived from IAPP (IAPP <span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">5-13 </span></span><span lang="JA">and IAPP</span><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">9-17</span></span><span lang="JA">) and common viral antigenic</span> minimal epitopes Flu MP <span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">58-66</span></span><span lang="JA">, CMV</span><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">495–503</span></span><span lang="JA">, EBV</span><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">280–288 </span></span><span lang="JA">and HIV</span><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">77–85 </span></span><span lang="JA">as controls.</span> <br/><b>Results</b>: <span lang="JA">A total of 36.4% of patients and 56.2% of healthy subjects showed a response</span> against IAPP <span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">5-13 </span></span><span lang="JA">peptide. No significant difference in response against this peptide was</span> noted between the patients and the healthy donors. With respect to peptide IAPP <span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">9-17</span></span><span lang="JA">,</span> although healthy subjects showed a higher mean number of spot forming cells than the patients, the difference was not significant; 36.4% of patients and 37.5% of controls responded to this peptide. The response of healthy subjects to the common viral peptides was stronger than that of the patients, though the result was not significant. <br/><b>Conclusions</b>: <span lang="JA">It is unlikely that IAPP would be a target for CD8</span><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA"><span style="font-family: Times New Roman+FPEF; font-size: xx-small;" lang="JA">+ </span></span><span lang="JA">T-cells in diabetic</span> patients; however, the trend observed toward a lower response of T2D patients against IAPP and common viral peptides may imply a decreased immune response in these patients.Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138311120140301The Effect of HLA-DRB1 Sharing between the Couples with Recurrent Pregnancy Loss on the Pregnancy Outcome after Leukocyte Therapy132016761ENBehrouzGharesi-FardInfertility Research CenterDepartment of Immunology, School of MedicineProteomics Laboratory,
School of Advanced Medical Sciences and Technologies,0000-0002-0162-3395RahilAskarinejad-BehbahaniStudent Research Center, Shiraz University of
Medical Sciences, Shiraz, IranShabnamBehdinStudent Research Center, Shiraz University of
Medical Sciences, Shiraz, IranJournal Article20160804<b>Background</b>: <span>Miscarriage is a common phenomenon complicating more than half of</span> pregnancies. Recurrent Pregnancy Loss (RPL) is defined as three or more pregnancies lost before the twentieth week of gestation. It is believed that abnormality in maternal immune reaction to fetus and sharing of HLA antigens might be associated with RPL. <br/><b>Objective</b>: <span>To investigate the effect of HLA-DRB1 sharing between the couples with</span> recurrent pregnancy loss on the pregnancy outcome after leukocyte therapy. <span><br/><b>Methods</b>:</span> Sixty primary RPL women who were immunized and followed after therapy (30 successful and 30 unsuccessful) and their husbands formed the cases of this study. In addition, one hundred healthy women were considered as the controls. HLA-DRB1 genotypes of all the cases and controls were checked by PCR-SSP method. <span><br/><b>Results</b>:</span> HLA typing indicated that the prevalence of HLA-DRB1 sharing (defined as at least one allele sharing) between the couples with unsuccessful outcomes was significantly higher compared to those with successful outcomes (63.3% vs. 23.3%, p<0.004). Moreover, HLA DRB1*07:01 allelic group was significantly more frequent in the patients with unsuccessful outcome compared to the controls (18.3% vs. 8%, p<0.04). <br/><b>Conclusion</b>: <span>Our results confirmed the role of HLA sharing in RPL and revealed that</span> HLA-DRB1 typing may be a valuable prognostic factor for the leukocyte therapy outcome.Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138311120140301Association of HLA-Class II and IgE Serum Levels in Pediatric Asthma212816762ENMahendraNarain MishraDr Lal Path Labs, National Reference Laboratory, Rohini, New DelhiPujaDudejaDepartment of Preventive and
Social Medicine, PGIMER, ChandigarhRakeshKumar GuptaDepartment of Pediatrics, Armed Forces Medical College, Pune,
Maharashtra, IndiaJournal Article20160804<b>Background</b>: <span>Pediatric bronchial asthma is associated with considerable morbidity. The</span> study was carried out to examine the association of Human Leukocyte Antigen (HLA)- Class II with the disease as we found no similar study on Asian Indian population. <br/><b>Objective</b>: <span>To define the HLA-Class II antigens in Asian Indian pediatric patients with</span> asthma. <span><br/><b>Methods</b>: </span><span>A total of 103 children with asthma and 152 controls were analysed</span> for HLA Class II (DRB1, DQB1and DPB1) by PCR-SSP (Sequence Specific Primers) method. Total serum IgE levels were determined by ELISA assay. <span><br/><b>Results</b>: </span><span>A positive</span> family history was recorded in 59 patients <span>(</span><span>57%) and 13 (8.5%) of healthy controls.</span> Serum IgE levels were more than normal range in 72% of the patients and 33% of healthy subjects with mean values of 4877 and 627 IU/ml, respectively. DRB1*04 and DQB1*03 showed significant positive relations while DRB1*15 showed a negative association with asthma. DQB1*02 was more common in healthy individuals but was not statistically significant. <span><br/><b>Conclusions</b>: </span><span>A positive association of the DR4/DQB1*03</span> and a negative association of DRB1*15 was seen with extrinsic bronchial asthma. However, more studies are required on larger populations to confirm the association of HLA Class II alleles in Indians before a particular allele can be labeled as being protective or causative for asthma.Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138311120140301Interleukin-17 Gene Expression and Serum Levels in Acute Rejected and non-Rejected Liver Transplant Patients293916763ENAfsoonAfshariDepartment of Molecular Genetics, Science and Research, Islamic Azad UniversityRaminYaghobiShiraz Transplant
Research Center, Shiraz University of Medical Sciences, Shiraz, IranMohammad HosseinKarimiShiraz Transplant
Research Center, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-2435-6277MojtabaDarbooieDepartment of Molecular Genetics, Science and Research, Islamic Azad UniversityNegarAzarpiraShiraz Transplant
Research Center, Shiraz University of Medical Sciences, Shiraz, IranJournal Article20160804<b>Background</b>: <span lang="KO">Interleukin-17 (IL-17), as a potent proinflammatory cytokine, has a</span> critical role in post liver transplant outcomes. However, there is not much information about the effects of IL-17 cytokine on acute liver rejection. <span><br/><b>Objective</b>: </span><span lang="KO">To evaluate the</span> role of IL-17 in post-liver transplant acute rejection. <span><br/><b>Methods</b>: </span><span lang="KO">Ninety seven adult liver</span> transplant patients who enrolled in this cross sectional study were divided into Non- Acute Rejected (Non-AR) and Acute Rejected (AR) patient groups. Three blood samples were collected from each patient in days 1, 4 and 7 post liver transplantation. The IL-17 mRNA levels were evaluated using an in-house real time PCR protocol. IL- 17 protein levels were also analyzed in Non-AR, AR and also control groups using ELISA method. <span><br/><b>Results</b>: </span><span lang="KO">The IL-17 mRNA expression level continuously increased in</span> AR patients in all days of follow-up post liver transplantation. IL-17 expression was, however, down regulated after day 4 post-transplant follow-up in Non-AR patients. Both IL-17 mRNA expression and protein levels were also significantly increased in AR patients compared with Non-AR ones. <span><br/><b>Conclusion</b>: </span><span lang="KO">Based on these findings,</span> significant increase of IL-17 mRNA and protein levels in AR patients highlights the important role of IL-17 in acute liver rejection.Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138311120140301Negative Association of Serum IL-6 and IL-17 with Type-II Diabetes Retinopathy404816764ENNadeemAfzalDepartment of Immunology, University of Health SciencesShakeelaZamanChildren Hospital and Institute of Child
Health, LahoreAneelaAsgharDepartment of Biochemistry, Sahiwal Medical College, SahiwalKhursheedJavedDepartment of Immunology, University of Health SciencesFaheemShahzadDepartment of Immunology, University of Health SciencesAbuZafarAmin Hayat Memorial
Diabetic Centre, LahoreAbdulHanan NagiDepartments of Pathology, University of Health Sciences, Lahore, PakistanJournal Article20160804<b>Background</b>: <span lang="JA">Diabetes mellitus (DM) is a health concern which leads to complications</span> such as retinopathy. Pakistan has 6.9 million people living with DM and this toll will be doubled by 2025. <span><br/><b>Objective</b>: </span><span lang="JA">To determine serum IL-6 and IL-17 of type 2 diabetes</span> mellitus (T2DM) patients with retinopathy. <span><br/><b>Methods</b>: </span><span lang="JA">In this cross-sectional casecontrol</span> study, 212 subjects enrolled which were categorized into 3 groups. Group-I included 30 subjects without diabetes, group-II consisted of 30 subjects with T2DM without retinopathy and group-III consisted of 152 subjects with T2DM and retinopathy. Serum IL-6 and IL-17 levels were determined by ELISA. Data was analysed using SPSS 17.0 and one way ANOVA to observe group mean differences. <br/><b>Results</b>: <span lang="JA">Longer mean duration of disease was detected in group-III than group-II</span> (p=0.007). Highest IL-6 level was detected in group-II and highest IL-17 level was detected in group-I. For IL-6, significant differences were detected among groups in total, between Group-I and Group-III and between Group-II and Group-III (p<0.0001 each). Regarding IL-17, significant differences were found among groups in total (p=0.002) and between Group-I and Group-III (p=0.001). No significant difference in the percentages of HbA1c observed between groups. <span><br/><b>Conclusions</b>: </span><span lang="JA">Age, gender and</span> duration of diabetes contribute to T2DM retinopathy. Serum IL-6 and IL-17 were inversely associated with T2DM retinopathy.Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138311120140301Primary Antibody Deficiencies at Queen Rania Children Hospital in Jordan: Single Center Experience495816765ENZeyadM.HabahbehImmunology, Allergy and Rheumatology Division, Queen Rania Children Hospital, King Hussein Medical
Center, Amman, JordanMohammadE Abu-ShukairImmunology, Allergy and Rheumatology Division, Queen Rania Children Hospital, King Hussein Medical
Center, Amman, JordanMohammadA. AlmutereenImmunology, Allergy and Rheumatology Division, Queen Rania Children Hospital, King Hussein Medical
Center, Amman, JordanRaedM. AlzyoudImmunology, Allergy and Rheumatology Division, Queen Rania Children Hospital, King Hussein Medical
Center, Amman, JordanAdelM WahadnehImmunology, Allergy and Rheumatology Division, Queen Rania Children Hospital, King Hussein Medical
Center, Amman, JordanJournal Article20160804<b>Background</b>: <span>Primary antibody deficiency, the most common primary</span> immunodeficiency disorder, represents a heterogeneous spectrum of conditions caused by a defect in any critical stage of B cell development and is characterized by impaired production of normal amounts of antigen-specific antibodies. <span><br/><b>Objective</b>: </span><span>This</span> retrospective study aimed at description and analysis of demographic, clinical, immunological features and complications of subjects diagnosed with primary antibody deficiency at a referral center in Jordan. <span><br/><b>Methods</b>: </span><span>The medical records of pediatric</span> patients who were diagnosed as primary antibody deficiency (PAD) during the period from January 2006 to June 2013 were reviewed. Patients were diagnosed as PADs based on the Pan-American Group for Immunodeficiency (PAGID) and the European Society for Immunodeficiency (ESID) diagnostic criteria. <span><br/><b>Results</b>: </span><span>A total number of 53</span> patients with PAD were identified; 37(70%) males and 16(30%) females, 16(30%) patients with congenital agammaglobulinemia, 16(30%) patients with common variable immunodeficiency, 4(7.5%) patients with IgG subclass deficiency, 10(19%) cases with transient hypogammaglobulinemia of infancy and 7(13.5%) patients as undefined PAD. The most common infection among patients was pneumonia (62%); followed by suppurative otitis media in 49% of patients. Cytopenia was the most noted autoimmune association and was found at prevalence of 22 %, other autoimmune associations (17%) including inflammatory arthritis, discoid lupus, inflammatory bowel disease, vasculitis and celiac disease. The prevalence of long-term complications was 58%, the most frequent ones were; stunted growth in 13%, bronchiectasis and lymphoproliferation in 11% for each. <span><br/><b>Conclusions</b>: </span><span>Our results indicated that congenital agammaglobulinemia</span> and common variable immunodeficiency are the most frequent primary antibody deficiency in our patients. The awareness of families, general population as well as primary health physicians is crucial in the establishment of early diagnosis and prompt commencement of appropriate therapy for PADs.Shiraz Institute for Cancer ResearchIranian Journal of Immunology1735-138311120140301A Case of Bruton’s Disease with Normal Immunoglobulin G Level596316766ENSoheilaAlyasinClinical Immunology and AllergyFarhadAbolnezhadianClinical Immunology and Allergy0000-0003-1197-7207AmirRezaeiPediatric Intensive Care, Department of Pediatrics, Division of
Immunology and Allergy, Namazi Hospital, Shiraz University of Medical Science, Shiraz, IranJournal Article20160804X-linked agamaglobulinemia (XLA) or Bruton’s disease is a genetic disease resulting from a mutation in the Bruton’s tyrosine kinase (Btk) gene. This mutation leads to B cell arrest during differentiation (1). This disease was first described by Ogden Bruton in 1952 (2). Approximately 85% of the affected subjects are male (3). This disorder is inherited as an X-linked recessive trait. Carrier females have no symptoms but have a 50% chance for transmission of the disorder to each of their sons. It is now possible to determine if the fetus of a carrier mother has XLA (4). The prevalence of the disease ranges from 1 in 10,000 to 1 in 50,000 (1). Half of the affected individuals are diagnosed during the first year of life and more than 90% of them are diagnosed up to fifth year (3). Diagnosis of the disease is suggested by lymphoid hypoplasia (minimal or no tonsillar tissue and no palpable lymph node) and total immunoglobulins level less than 100 mg/dl. Isohemagglutinins and antibodies to antigens given during routine immunization are abnormally low in this disorder as well. Flow cytometry is an important test for this diagnosis (5). Patients with XLA are protected for the first few months of life by maternal antibody and therefore do not typically present clinically with infection until after 6 months of age, when the maternally-derived antibody level decreases significantly. After diagnosis, treatment includes replacement of intravenous immunoglobulin (IVIG), which significantly reduces the risk of infection (6). The most common organisms affecting these patients are <em><span>Haemophilus influenza</span></em><span>, </span><em><span>Streptococcus pneumonia </span></em><span>and</span> Staphylococcus aureus <span>(3).</span> Based on our knowledge, 4 cases of XLA patients with normal IgG levels (above 500 mg/dl) and 5 cases of XLA subjects with near normal IgG levels (400-500 mg/dl) have been reported in the world (7). Here, we report a case of Bruton’s disease as the fifth case with normal serum IgG level.