Maja Stojanovic; Zorana Andric; Dusan Popadic; Marija Stankovic Stanojevic; Rada Miskovic; Dragana Jovanovic; Aleksandra Peric Popadic; Jasna Bolpacic; Vesna Tomic-Spiric; Sanvila Raskovic
Abstract
Background: Takayasu arteritis (TA) is a systemic vasculitis, affecting mainly the aorta and its branches. Objective: To analyze the HLA class I and class II alleles in patients with TA and explore their relationship with clinical and demographic characteristics, and potential significance in prognosis. ...
Read More
Background: Takayasu arteritis (TA) is a systemic vasculitis, affecting mainly the aorta and its branches. Objective: To analyze the HLA class I and class II alleles in patients with TA and explore their relationship with clinical and demographic characteristics, and potential significance in prognosis. Methods: Twenty-five, unrelated TA patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and the HLA-DQB1 loci. The frequencies of the HLA-A, HLA-B, and the HLA-DRB1 were compared with a control group of 1992, while the HLA-C and the HLA-DQB1 were compared with a group of 159 healthy, unrelated individuals. Results: Among TA patients, 5/25 (20%) were identified as the HLA-B*52 carriers. There was a significant difference in the HLA-B*52 allele frequency in the TA patients (10%) compared with the healthy controls (1.2%). Moreover, presence of the HLA-B*52 was associated with significantly earlier disease onset, more severe clinical presentations, and a poorer response to treatment. The HLA-C*03 was detected in 32% of patients and was present exclusively in those with a clinically mild form of the TA, indicating a putative protective effect. Conclusion: These findings indicate that the HLA-B*52 allele contributes to a higher susceptibility to the TA whereas the HLA-C*03, can be a protective factor in the TA.
Zahra Mehraji; Ali Farazmand; Alireza Esteghamati; Sina Noshad; Maryam Sadr; Somayeh Amirzargar; Mir Saeed Yekaninejad; Aliakbar Amirzargar
Volume 14, Issue 3 , September 2017, , Pages 223-230
Abstract
Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility ...
Read More
Background: Graves’ disease (GD), a highly rampant autoimmune disorder of the thyroid gland, is responsible for 60-80% of the clinical cases of hyperthyroidism. Over the past decades, genetic association studies have identified several GD susceptibility loci in CTLA-4, TSHR and major histocompatibility complex regions. The information on the association between the human leukocyte antigens (HLA) and GD among Iranians is scarce. Objective: To identify HLA polymorphisms that might confer susceptibility or protect against GD. Methods: Eighty unrelated patients with a confirmed diagnosis of GD were included in the case group. The control group consisted of 180 unrelated healthy individuals with normal thyroid function tests. The polymerase chain reaction with sequence specific primers (PCR-SSP) method was used for HLA typing. Results: Frequencies of HLA-A*68 (15.6% vs. 4.2%, p=0.004) and B*08 (8.8% vs. 2.5, p=0.030) were significantly higher in patients with GD compared with healthy controls. No patients with GD had HLA-A*33, whereas it was found in 7.0% of the controls (p=0.011). HLA-DQB1*0201 was significantly less frequent among patients with GD (15.6% vs. 26.8%, p=0.040). Additionally, patients with GD were significantly less bound to have HLA-DQA1*0201 (6.2% vs. 15.1%, p=0.045). Concerning allelic distributions, no noticeable difference was found between GD patients with and without Graves’ ophthalmopathy (p>0.05 in all cases). Conclusion: In the Iranian population, HLA-A*68 and -B*08 confer susceptibility to GD, whereas HLA-A*33, -DQB1*0201, and -DQA1*0201 appear to have protective roles.
Farhad Shahsavar; Tahereh Mousavi; Alireza Azargoon; Kobra Entezami
Volume 9, Issue 1 , March 2012, , Pages 39-47
Abstract
Background: Natural killer (NK) cells are the effector cells of innate immunity that respond to infection and tumor. Interactions between killer cell immunoglobulin like receptors (KIR) and human leukocyte antigen (HLA) class I molecules regulate NK cells responses to eliminate infected and transformed ...
Read More
Background: Natural killer (NK) cells are the effector cells of innate immunity that respond to infection and tumor. Interactions between killer cell immunoglobulin like receptors (KIR) and human leukocyte antigen (HLA) class I molecules regulate NK cells responses to eliminate infected and transformed cells. Objective: To investigate the impact of KIR genes, HLA ligand genes, and KIR-HLA combinations on susceptibility to tuberculosis (TB) in Lur population of Iran. Methods: The genomic DNA of 50 patients with TB from Lorestan province of Iran was genotyped for sixteen KIR genes and their five major HLA class I ligands were determined by a polymerase chain reaction-sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy unrelated Iranian individuals. Results: In Lur population of Iran, a significant decrease in frequency of KIR3DS1 was found in TB patients compared to control group (24% vs. 44.5%, OR=0.394, CI=0.194-0.798, p=0.013). Also, among the three activating genes that may use HLA class I molecules as their ligands, a significant decrease was shown in frequency of KIR3DS1 with HLA-B Bw4Ile80 ligand in TB patients compared to control group (4% vs. 23%, OR=0.14, CI=0.033-0.596, p=0.004). Conclusion: These findings imply a genetic imbalance between activating and inhibitory KIR genes and KIR-HLA combinations in Lur TB patients. Low level of activating KIR3DS1 and its combination with HLA-B Bw4Ile80 ligand might have an influence on the susceptibility to TB in Lur population of Iran.
Tahereh Mousavi; Hadi Poormoghim; Maziar Moradi; Nader Tajik; Farhad Shahsavar; Behnam Asadifar
Volume 7, Issue 2 , June 2010, , Pages 88-95
Abstract
Background: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). Objective: We investigated the HLAC and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence ...
Read More
Background: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). Objective: We investigated the HLAC and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing spondylitis (AS) susceptibility, alone or in combination. Methods: We typed 40 AS patients and 40 normal controls for HLA-C asn80 (group 1) and HLA-C lys80 (group 2), HLA-B Bw4thero, HLA-B Bw4iso and HLA-A Bw4 alleles by PCR-SSP method. We also assessed the expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DL1 and KIR2DS4 by flow cytometry. The Pearson chi-square or Fisher exact test was performed for statistical analysis. Results: The frequency of HLA-B Bw4iso but not HLA-B Bw4thero and HLA-A Bw4, ligand for the inhibitory KIR3DL1, was significantly reduced in AS patients as compared with controls (p<0.01). No significant differences were observed in gene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Although no differences were found in the expression of KIR receptors between AS and normal subjects, we found that expression of KIR3DL1 in the presence of HLA Bw4-Biso gene was reduced in patients with AS compared to healthy controls (p<0.009). Conclusion: We conclude that HLA-B Bw4iso, the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our results suggest that besides the HLA and KIR genotype, expression levels of KIRs may be involved in the pathogenesis of AS disease
Farhad Shahsavar; Nader Tajik; Kobra-Zinat Entezami; Masoomeh Fallah Radjabzadeh; Behnam Asadifar; Kamran Alimoghaddam; Mohammadreza Ostadali Dahaghi; Arash Jalali; Andisheh Ghashghaie; Ardeshir Ghavamzadeh
Volume 7, Issue 1 , March 2010, , Pages 8-17
Abstract
Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility ...
Read More
Background: Interaction between killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA) class I molecules is important for regulation of natural killer (NK) cell function. Objective: The aim of this study was to investigate the impact of compound KIR-HLA genotype on susceptibility to acute leukemia. Methods: Cohorts of Iranian patients with acute myeloid leukemia (AML; n=40) and acute lymphoid leukemia (ALL; n=38) were genotyped for seventeen KIR genes and their three major HLA class I ligand groups (C1, C2, Bw4) by a combined polymerase chain reaction–sequence-specific primers (PCR-SSP) assay. The results were compared with those of 200 healthy control individuals. Results: We found a significantly decreased frequency of KIR2DS3 in AML patients compared to control group (12.5% vs. 38%, odds ratio=0.23, p=0.0018). Also, the KIR3DS1 was less common in AML group than controls (27.5% vs. 44.5%, p=0.0465, not significant after correction). Other analyses including KIR genotypes, distribution and balance of inhibitory and activating KIR+HLA combinations, and co-inheritance of activating KIR genes with inhibitory KIR+HLA pairs were not significantly different between leukemia patients and the control group. However, in AML patients a trend toward less activating and more inhibitory KIR-HLA state was observed. Interestingly, this situation was not found in ALL patients and inhibition enhancement through increase of HLA ligands and inhibi-tory combinations was the main feature in this group. Conclusion: Our findings may suggest a mechanism for escape of leukemic cells from NK cell immunity.
Ghasem Solgi; Gholamreza Pourmand; Abdorasool Mehrsai; Mohsen Tahei-mahmoudi; Mohammad Hossein Nicknam; Mohammad Ebrahimi Rad; Ali Seraji; Amirabbas Asadpoor; Bita Ansaripor; Behrouz Nikbin; Aliakbar Amirzargar
Volume 7, Issue 1 , March 2010, , Pages 18-29
Abstract
Background: Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. Objective: The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concur-rent donor bone marrow cell infusion ...
Read More
Background: Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. Objective: The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concur-rent donor bone marrow cell infusion (DBMI). Methods: Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre- and post-transplant (days 14, 30, and 90) sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA spe-cific panel for antibody specification. Results: Of 40 patients, 9 (22.5%) experienced acute rejection episodes (ARE) (6/20 cases in non-infused versus 3/20 in DBMI patients). The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones (88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively). A total of 10% (4/40) of patients developed donor specific anti-HLA antibodies (DSA) and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Con-clusion: Our findings reveal an association between pre- and post-transplant anti-HLA an-tibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts.
Raja Rajalingam
Volume 4, Issue 2 , June 2007, , Pages 61-78
Abstract
Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the ...
Read More
Natural killer (NK) cells are a subset of lymphocytes which play a crucial role in early innate immune response against infection and tumor transformation. Furthermore, they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF) prompting adaptive immu-nity. NK cells distinguish the unhealthy cells from the healthy ones through an array of cell-surface receptors. Human NK cells use inhibitory and activating killer cell Ig-like receptors (KIR) as primary probe to discriminate between healthy and unhealthy cells. The inhibitory KIRs recognize HLA class I molecules and trigger signals that stop NK killing. The activating KIRs are believed to recognize the determinants associated with infections and tumors, and trigger signals that activate NK killing. Therefore, the effec-tor function of a given NK cell depends upon the receptors that it expresses and ligands that it recognizes on the targets. Genes encoding KIRs and HLA ligands are located on different chromosomes, and vary in number and type. The independent segregation of KIR and HLA genes results in variable KIR-HLA combinations in individuals, which may determine the individual’s immunity and susceptibility to disease.
Houshang Rafatpanah; Vera Pravica; Reza FaridHosseini; Abbas Tabatabaei; Wiliam Ollier; Kay Poulton; Wendy Thomson; Ian Hutchinson
Volume 4, Issue 2 , June 2007, , Pages 94-100
Abstract
Background: Human T cell lymphotropic virus type I (HTLV-I)-associated myelopa-thy/tropical spastic paraparesis (HAM/TSP) is an inflammatory disease which occurs in less than 2% of HTLV-I -infected individuals. High proviral load, high HTLV-I-specific CD8+ cytotoxic T lymphocyte frequency (CTL) and host ...
Read More
Background: Human T cell lymphotropic virus type I (HTLV-I)-associated myelopa-thy/tropical spastic paraparesis (HAM/TSP) is an inflammatory disease which occurs in less than 2% of HTLV-I -infected individuals. High proviral load, high HTLV-I-specific CD8+ cytotoxic T lymphocyte frequency (CTL) and host genetic factors such as HLA all appear to be associated with HTLV-I infection. Previous studies have shown that HLA-DRB1*01 increases the risk of HAM/TSP in Japanese HTLV-I infected individu-als. Objective: To investigate the association between HLA class II DRB1 alleles and HLA class I alleles (HLA-Cw*08, B54, A*02 and A-30) in HTLV-I infected individu-als in Mashhad. Methods: Here we determined the frequency of HLA class II DRB1, using INNO-LIPA reverse hybridization line probe assay, and HLA class I alleles (HLA-Cw*08,B54, A*02 and A-30) by PCR-SSCP method in healthy controls, HAM/TSP patients and HTLV-I infected individuals born and resident in Mashhad. Results: The frequency of HLA-DRB1*01 alleles in this population was different from other areas of Iran. The frequency of HLA-DRB1*01 was significantly increased in HAM/TSP patients compared with carriers (p 0.028; OR=9.4). The frequency of HLA-Cw*08 was also significantly increased in HAM/TSP patients compared with controls (p=0.03; OR=13.5). Conclusion: Our results may suggest that possession of HLA-DRB1*01 increases the risk of HAM/TSP in HTLV-I-infected individuals and HLA-Cw*08 correlates with low CTL immune response in HAM/TSP patients.
Nader Tajik; Tohid Kazemi; Aliakbar Delbandi; Ahad Ghods; Alireza Salek Moghaddam
Volume 3, Issue 4 , December 2006, , Pages 150-156
Abstract
Background: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphisms in cytokines might also be important in the quality of allogeneic immune response. Objective: To evaluate the influence of HLA-DR matching and a number of cytokine gene polymorphisms on acute rejection after living-unrelated ...
Read More
Background: In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphisms in cytokines might also be important in the quality of allogeneic immune response. Objective: To evaluate the influence of HLA-DR matching and a number of cytokine gene polymorphisms on acute rejection after living-unrelated donor (LURD) kidney transplantation. Methods: A total of 42 renal transplants performed at Hashemi Nejad Kidney Hospital (Tehran/Iran) and followed up for 3 months post-transplantation were included. Using PCR-SSP, HLA-DR alleles (DR1- 18) of recipients and donors and gene polymorphisms in TNF-a, TGF-b1, IL-10, IL- 6, and IFN-g of recipients were determined. Results: Acute rejection was observed in 11(26.2%) of renal recipients. The frequency of one and two HLA-DR mismatches in rejector group was 2(18.2%) and 9(81.8%) and in non-rejector group was 13(41.9%) and 17(54.8%), respectively. HLA-DR incompatibility was not significantly higher in rejector (1.82 0.40) compared with non-rejector (1.52 0.57) recipients (P=0.069) and more than half of non-rejectors had completely mismatched HLA-DR antigens with donors. Polymorphisms associated with the mentioned cytokines had no correlation with acute rejection. Conclusion: The predictive value of HLA-DR mismatching for acute rejection is not as prominent in LURD kidney transplantation as in the cadaveric one. In addition, we failed to demonstrate an association between combined cytokine genotypes and HLA-DR matching with acute rejection. Further and more detailed immunogenetic investigations are required in order to have a better prediction of the transplant outcome.
Zahra Amirghofran
Volume 2, Issue 1 , March 2005, , Pages 29-35
Abstract
Background: Perforin is known to be important in cytolytic activity mediated by natural killer (NK) cells. Objective: To study the relationship between the efficiency of NK and lymphokine-activated killer (LAK) cells activity, and the expression of perforin and HLA class I molecules. Methods: ...
Read More
Background: Perforin is known to be important in cytolytic activity mediated by natural killer (NK) cells. Objective: To study the relationship between the efficiency of NK and lymphokine-activated killer (LAK) cells activity, and the expression of perforin and HLA class I molecules. Methods: LAK cells were generated by in vitro culturing of human peripheral blood lymphocytes (PBLs) in the presence of human recombinant interleukin-2 (rIL-2). Cytotoxic activity was measured at different intervals of activation by MTT colorimetric assay using different human tumor cell lines. Immunocytochemical staining of molecules was performed on LAK/NK cells using specific monoclonal antibodies and Biotin-conjugated anti-immunoglobulin. Results: LAK/NK killing against Fen and two other cell lines, KB and Scaber showed that at day 9 and 15 of activation, 57% to 60% and 45.5% to 92.5% of Fen cells were killed at different E/T ratios. At the same time, the maximum percent killing against Scaber and KB cell lines was 47.3 and 54.3 at 5/1 ratio, respectively, showing that Fen cells were more sensitive than the two other cells. Time-course experiments using Fen cell line demonstrated 60.0, 83.9 and 34.8 percent killing at days 9, 15 and 22 at 10/1 E/T ratios. When other E/T ratios were investigated, a similar profile was observed. The maximum activity was at day 15 and 5/1 E/T ratio (92.5%). In immunocytochemical staining of activated LAK cells, 75.9% to 86.3% of LAK cells expressed HLA class I molecules. Perforin expression changed from 30.3% at day 7 to 42.7% at day 17 followed by a decrease to 27.9% at day 24. Conclusion: These data indicate that perforin expression is closely correlated with NK/LAK killing activity.
