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Polymorphism of Leukocyte and Erythrocyte Antigens in Chronic Kidney Disease Patients in Southern Brazil  [PDF]
Roger Haruki Yamakawa, Patricia Keiko Saito, Waldir Veríssimo da Silva Junior, Luiz Carlos de Mattos, Sueli Donizete Borelli
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0084456
Abstract: We investigated the polymorphism of human leukocyte antigens (HLA) and Duffy erythrocyte antigens in chronic kidney disease (CKD) patients in southern Brazil. One hundred and eighty-three CKD patients, over 18 years old, on hemodialysis, were included. HLA-A, -B and -DRB1 typing was performed using the LABType?SSO (One Lambda, Inc.). Duffy phenotypes were determined by gel column agglutination using anti-Fya and anti-Fyb monoclonal anti-sera. The patients' predominant ages ranged between 51 and 70 years (43%) and the predominant gender, ethnic group and dialysis period were, respectively, male (62%), white (62%) and 1–3 years (40%). The highest and lowest frequencies of Duffy phenotypes were Fy(a+b+) and Fy(a?b?), respectively. Nineteen HLA-A, 30 HLA-B and 13 HLA-DRB1 allele groups were identified. The most frequent HLA allele groups were HLA-A*01, -A*02, -A*03, -A*11, -A*24; HLA-B*07, -B*15, -B*35, -B*44, -B*51; HLA-DRB1*03, -DRB1*04, -DRB1*07, -DRB1*11 and -DRB1*13. Statistically significant differences were observed in the Duffy and HLA polymorphisms compared between CKD patients and healthy subjects. The Fy(a+b?) phenotype (p<0.0001, OR = 2.56, 95% CI = 1.60–4.07) was the most frequent in the patients (p<0.05), and the Fy(a+b+) phenotype (p = 0.0039, OR = 1.71, 95% CI = 1.18–2.51) was the most frequent in the healthy subjects in the same region of Paraná state (p<0.05). Regarding HLA, the HLA-B*42, -B*45, -B*51 and -DRB1*03 allele groups were the most frequent in the patients (p<0.05), and the HLA-B*44 allele group was the most frequent in the healthy subjects in the same region of Brazil (p<0.05). The polymorphism of these two markers among CKD patients in southern Brazil and healthy subjects of other studies, suggests that these markers might be involved with CKD development. Further studies should be undertaken to analyze the markers' influence on CKD and the long-term results from kidney transplantation.
Human leucocyte antigens and cytokine gene polymorphisms and tuberculosis  [cached]
Akgunes A,Coban A,Durupinar B
Indian Journal of Medical Microbiology , 2011,
Abstract: Purpose: Several genes encoding different cytokines and human leucocyte antigens (HLA) may play crucial roles in host susceptibility to tuberculosis (TB). Our objective was to investigate whether these genes might be associated with protection from or susceptibility to TB. Materials and Methods: Genomic DNA from patients with TB (n = 30) and ethnically matched controls (n = 30) was genotyped by using sequence-specific primers-polymerase chain reaction and sequence-specific oligonucletid methods. Results: Our results demonstrated that HLA-CwFNx0101 [P = 0.05, odds ration (OR) (95% confidence interval) = 2.269 (1.702-3.027)] allele frequency was significantly more common in TB patients than in healthy controls, and HLA-CwFNx0101 may be associated with susceptibility to TB. Analysis of cytokine allele frequencies showed that interleukin (IL)-10, -819 C and -592 C alleles was significantly more common in TB patients than in controls (pc: 0.038 and 0.017, respectively). From the IL-10 cluster, a positive significant difference was found at positions -1082 and -592 C/C (pc: 0.027 and 0.054, respectively) genotypes. Although these differences could be explained by the highest frequency of C/C and G/G homozygous patients with TB, in contrast to the control group, statistically significant differences for the C/C genotype however were lost after Bonferroni correction of the P-values. Conclusion: Altogether, our results suggest that the polymorphisms in HLA (class I) and cytokine (IL-10) genes may affect the susceptibility to TB and increase the risk of developing the disease.
Analysis of human leukocyte antigens class II-DR in Brazilian children and adolescents with systemic lupus erythematosus
Liphaus, Bernadete de L.;Goldberg, Anna Carla;Kiss, Maria Helena B.;Silva, Clovis A. A.;
Revista do Hospital das Clínicas , 2002, DOI: 10.1590/S0041-87812002000600006
Abstract: objective: to analyze the frequency of human leukocyte antigens class ii-dr in children and adolescents with systemic lupus erythematosus. patients and methods: fifty-fivebrazilian systemic lupus erythematosus children and adolescents and 308 healthy individuals were studied. gender, race, and age of onset of systemic lupus erythematosus were recorded. the human leukocyte antigens typing of class ii-dr was carried out by polymerase chain reaction amplification with sequence-specific primers (pcr-ssp). data were analyzed statistically using the chi square test with yates' correction, fisher's exact test, and bonferroni's correction. results: human leukocyte antigen-dr 15 was the most frequently detected antigen in this group of children and adolescents, and it also occurred more frequently in the female group, in children with onset of systemic lupus erythematosus between 0 and 9 years and between 10 to 14 years, and in the black race group, but these associations were not statistically significants. conclusion: in this group of children and adolescents with a high degree of racial admixture, we could not verify a significant association between human leukocyte antigens class ii-dr and systemic lupus erythematosus.
Analysis of human leukocyte antigens class II-DR in Brazilian children and adolescents with systemic lupus erythematosus  [cached]
Liphaus Bernadete de L.,Goldberg Anna Carla,Kiss Maria Helena B.,Silva Clovis A. A.
Revista do Hospital das Clínicas , 2002,
Abstract: OBJECTIVE: To analyze the frequency of human leukocyte antigens class II-DR in children and adolescents with systemic lupus erythematosus. PATIENTS AND METHODS: Fifty-fiveBrazilian systemic lupus erythematosus children and adolescents and 308 healthy individuals were studied. Gender, race, and age of onset of systemic lupus erythematosus were recorded. The human leukocyte antigens typing of class II-DR was carried out by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP). Data were analyzed statistically using the chi square test with Yates' correction, Fisher's exact test, and Bonferroni's correction. RESULTS: Human leukocyte antigen-DR 15 was the most frequently detected antigen in this group of children and adolescents, and it also occurred more frequently in the female group, in children with onset of systemic lupus erythematosus between 0 and 9 years and between 10 to 14 years, and in the Black race group, but these associations were not statistically significants. CONCLUSION: In this group of children and adolescents with a high degree of racial admixture, we could not verify a significant association between human leukocyte antigens class II-DR and systemic lupus erythematosus.
HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens  [PDF]
Shinji Amari,Ryoichi Kataoka,Takashi Ikegami,Noriaki Hirayama
International Journal of Medicinal Chemistry , 2013, DOI: 10.1155/2013/690513
Abstract: The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0?? in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures. 1. Introduction The cause of various diseases involves the human leukocyte antigen (HLA) system which is the human version of the major histocompatibility complex. The HLA genes involved in the immune response fall into two classes, I and II, which are structurally and functionally different. Typical diseases associated with HLA molecules are autoimmune diseases [1] and infectious diseases [2]. The association between specific HLA alleles and adverse drug reactions which frequently cause significant morbidity and mortality for patients is also widely known [3]. A reliable three-dimensional (3D) structure of the particular HLA allele responsible for the specific event is essential to understand the underlying molecular mechanism in order to develop effective therapeutic agents or/and countermeasures. Since the pioneering work by Wiley et al. [4], various crystal structures of the HLA molecules have been disclosed so far. The crystal structures have shown that the peptide-binding groove of an HLA molecule consists of two parts, a floor and two walls. Although this canonical topology is highly conserved among different alleles, certain structural differences exist depending on the alleles. Therefore, the 3D structure of a particular HLA molecule is required for HLA studies. The HLA genes are the most polymorphic in the human genome and there are a large number of allelic variations. In the
Evaluation of the Humoral Immune Response to Human Leukocyte Antigens in Brazilian Renal Transplant Candidates  [PDF]
Patricia Keiko Saito, Roger Haruki Yamakawa, Erica Pereira Aparecida, Waldir Verissimo da Silva Júnior, Sueli Donizete Borelli
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100270
Abstract: Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.
Comparison of Visceral Leishmaniasis Diagnostic Antigens in African and Asian Leishmania donovani Reveals Extensive Diversity and Region-specific Polymorphisms  [PDF]
Tapan Bhattacharyya ,Marleen Boelaert,Michael A. Miles
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002057
Abstract: Background Visceral leishmaniasis (VL), caused by infection with Leishmania donovani complex, remains a major public health problem in endemic regions of South Asia, East Africa, and Brazil. If untreated, symptomatic VL is usually fatal. Rapid field diagnosis relies principally on demonstration of anti-Leishmania antibodies in clinically suspect cases. The rK39 immunochromatographic rapid diagnostic test (RDT) is based on rK39, encoded by a fragment of a kinesin-related gene derived from a Brazilian L. chagasi, now recognised as L. infantum, originating from Europe. Despite its reliability in South Asia, the rK39 test is reported to have lower sensitivity in East Africa. A reason for this differential response may reside in the molecular diversity of the rK39 homologous sequences among East African L. donovani strains. Methodology/Principal Findings Coding sequences of rK39 homologues from East African L. donovani strains were amplified from genomic DNA, analysed for diversity from the rK39 sequence, and compared to South Asian sequences. East African sequences were revealed to display significant diversity from rK39. Most coding changes in the 5′ half of repeats were non-conservative, with multiple substitutions involving charge changes, whereas amino acid substitutions in the 3′ half of repeats were conservative. Specific polymorphisms were found between South Asian and East African strains. Diversity of HASPB1 and HASPB2 gene repeat sequences, used to flank sequences of a kinesin homologue in the synthetic antigen rK28 designed to reduce variable RDT performance, was also investigated. Non-canonical combination repeat arrangements were revealed for HASPB1 and HASPB2 gene products in strains producing unpredicted size amplicons. Conclusions/Significance We demonstrate that there is extensive kinesin genetic diversity among strains in East Africa and between East Africa and South Asia, with ample scope for influencing performance of rK39 diagnostic assays. We also show the importance of targeted comparative genomics in guiding optimisation of recombinant/synthetic diagnostic antigens.
The Influence of Human Leukocyte Antigen and IL-10 Gene Polymorphisms on Hepatitis B Virus Outcome
Amitis Ramezani,Mohammad Banifazl,Setareh Mamishi,Masoomeh Sofian
Hepatitis Monthly , 2012,
Abstract: Context: The clinical outcome of hepatitis B virus (HBV) infection is variable, ranging from spontaneous recovery to an inactive carrier state, chronic hepatitis, occult HBV infection, liver cirrhosis, or hepatocellular carcinoma.Evidence Acquisition: This variable pattern and clinical outcomes of the infection were mainly determined by virological and host genetic factors. Since the most of host genetic factors associated with HBV infection have currently focused on human leukocyte antigen (HLA) associations and interleukin (IL)-10 gene polymorphisms, this review focuses on the recent progresses in these issues to provide prognostic markers for the outcome of HBV infection.Results: A study on serum levels of IL-10 in occult HBV infected patients reported that the higher level of IL-10 production may suppress function of the immune system against HBV in patients with occult HBV infection. IL-10 promoter polymorphism at position -592 is associated with susceptibility to occult HBV infection.Conclusions: Findings of this study suggest that the host HLA polymorphism is an important factor in determining outcome of HBV infection but regarding IL-10 gene promoter polymorphisms, we are still have a long way to achieve a de nite conclusion.
Human Leukocyte Antigens and HIV Type 1 Viral Load in Early and Chronic Infection: Predominance of Evolving Relationships  [PDF]
Jianming Tang,Rakhi Malhotra,Wei Song,Ilene Brill,Liangyuan Hu,Paul K. Farmer,Joseph Mulenga,Susan Allen,Eric Hunter,Richard A. Kaslow
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0009629
Abstract: During untreated, chronic HIV-1 infection, plasma viral load (VL) is a relatively stable quantitative trait that has clinical and epidemiological implications. Immunogenetic research has established various human genetic factors, especially human leukocyte antigen (HLA) variants, as independent determinants of VL set-point.
Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo
Thorsten Peters,Wilhelm Bloch,Oliver Pabst,Claudia Wickenhauser,Claudia Uthoff-Hachenberg,Susanne V. Schmidt,Georg Varga,Stephan Grabbe,Daniel Kess,Tsvetelina Oreshkova,Anca Sindrilaru,Klaus Addicks,Reinhold F rster,Werner Müller,Karin Scharffetter-Kochanek
Clinical and Developmental Immunology , 2012, DOI: 10.1155/2012/450738
Abstract: Absence of β2 integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−). CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)21 acetyl chicken γ globulin (NP21-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.
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