Human leukocyte antigen class-II DRB1 alleles and Giardia lamblia infection in children: A case-control study

Objective: To compare the genotype frequencies of HLA class- II DRB1 alleles in Giardia (G.) lamblia-infected children. Methods: A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examination to detect G. lamblia infection, and to exclude other intestinal pathogens. On the basis of their microscopic findings, a group of 80 children were chosen as giardiasis cases, another 80 children were confirmed as Giardia free control group by immunochromatographic test, and the remaining children were excluded. Both giardiasis and control groups were then subjected to blood examination to identify their genetic type of HLA-DRB1 alleles. Results: HLA class-II DRB1∗03:01 and DRB1∗13:01 alleles were significantly associated with G. lamblia infection (P<0.001 for each variable). On the other hand, HLA class-II DRB1∗04:02, DRB1∗10:01, DRB1∗14:01 and DRB1∗15:01 alleles were significantly demonstrated in Giardia free children. However, other HLA-DRB1 alleles did not show any significant association with giardiasis. Conclusions: HLA class-II DRB1∗03, DRB1∗13, DRB1∗04, DRB1∗10, DRB1∗14 and DRB1∗15 alleles may be involved in the establishment of host immune response to G. lamblia infection.

Human leukocyte antigen class-II DRB1 alleles and Giardia lamblia infection in children: A case-control study

Objective: To compare the genotype frequencies of HLA class- II DRB1 alleles in Giardia (G.) lamblia-infected children. Methods: A total of 490 Egyptian children aged 2-16 years were subjected to microscopic stool examination to detect G. lamblia infection, and to exclude other intestinal pathogens. On the basis of their microscopic findings, a group of 80 children were chosen as giardiasis cases, another 80 children were confirmed as Giardia free control group by immunochromatographic test, and the remaining children were excluded. Both giardiasis and control groups were then subjected to blood examination to identify their genetic type of HLA-DRB1 alleles. Results: HLA class-II DRB1∗03:01 and DRB1∗13:01 alleles were significantly associated with G. lamblia infection (P<0.001 for each variable). On the other hand, HLA class-II DRB1∗04:02, DRB1∗10:01, DRB1∗14:01 and DRB1∗15:01 alleles were significantly demonstrated in Giardia free children. However, other HLA-DRB1 alleles did not show any significant association with giardiasis. Conclusions: HLA class-II DRB1∗03, DRB1∗13, DRB1∗04, DRB1∗10, DRB1∗14 and DRB1∗15 alleles may be involved in the establishment of host immune response to G. lamblia infection.

Acute disseminated encephalomyelitis: clinical features, HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602, and HLA DPA1*0301 allelic association study / Encefalomielite aguda disseminada: características clínicas e estudo de associação com os alelos HLA DRB1*1501, HLA DRB1*1503, HLA DQA1*0102, HLA DQB1*0602 e DPA1*0301

We evaluated the frequency, demographic, clinical, disability evolution and genetic association of HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 and DPA1*0301 alleles in patients diagnosed as acute disseminated encephalomyelitis (ADEM) among a population of CNS demyelinating diseases. Fifteen patients (8.4 percent) of our series were diagnosed as ADEM. The mean age onset was 35.23 years (range 12 to 77), 53.3 percent were male and follow-up range was 8.5 to 16 years. Two cases (13.3 percent) had a preceding infection before neurological symptoms, one presented a parainfectious demyelinating, and one case had been submitted to hepatitis B vaccination four weeks before the clinical onset. The EDSS range was 3.0 to 9.5. Eight patients (53.3 percent) presented MRI with multiple large lesions. CSF was normal in 73.3 percent. The severe disability observed at EDSS onset improved in 86.66 percent patients. The genetic susceptibility for ADEM was significantly associated with the HLA DQB1*0602, DRB1*1501 and DRB1*1503 alleles (<0.05) in monophasic ADEM.

Avaliamos as frequencia, características demográficas, clínicas e de associação genética dos alelos HLA DRB1*1501, DRB1*1503, DQA1*0102, DQB1*0602 e DPA1*0301 em pacientes com diagnóstico de encefalomielite aguda disseminada (ADEM) em população com doença desmielinizante do SNC. Quinze (8,4 por cento) pacientes de nossa série foram diagnosticados como ADEM. A média de idade foi 35,23 anos (variando entre 12 e 77), 53,3 por cento eram homens e o tempo de acompanhamento variou entre 8,5 e 16 anos. Dois casos (13,3 por cento) apresentaram infecção prévia, um apresentou processo desmielinizante para infeccioso e outro havia se submetido a vacinação para hepatite B quatro semanas antes. O EDSS variou entre 3,0 e 9,5. Oito pacientes (53,3 por cento) apresentaram grandes lesões na RM. O LCR foi normal em 73,3 por cento. A incapacidade grave quantificada pelo EDSS foi seguida de melhora importante em 86,6 por cento dos pacientes. A susceptibilidade genética na ADEM foi significativamente associada com os alelos HLA DQB1*0602, DRB1*1501 e DRB1*1503 (p<0,05) nos pacientes com quadro monofásico.

Distribution of the human leukocyte antigen class II alleles in Brazilian patients with chronic hepatitis C virus infection

Hepatitis C virus (HCV) infection is a global medical problem. The current standard of treatment consists of the combination of peginterferon plus ribavirin. This regimen eradicates HCV in 55 percent of cases. The immune response to HCV is an important determinant of disease evolution and can be influenced by various host factors. HLA class II may play an important role in immune response against HCV. The objective of the present study was to determine the distribution of HLA class II (DRB1 and DQB1) alleles, their association with chronic HCV infection and their response to interferon therapy. One hundred and two unrelated white Brazilian patients with chronic HCV infection, 52 responders (45 males and 7 females) and 50 non-responders (43 males and 7 females) to antiviral treatment, were included in the study. Healthy Brazilian bone marrow donors of Caucasian origin from the same geographic area constituted the control group (HLA-DRB1, N = 99 and HLA-DQB1, N = 222 individuals). HLA class II genotyping was performed using a low-resolution DRB1, DQB1 sequence-specific primer amplification. There were higher frequencies of HLA-DRB1*13 (26.5 vs 14.1 percent) and HLA-DQB1*02 (52.9 vs 38.7 percent) in patients compared with controls; however, these were not significantly different after P correction (Pc = 0.39 and Pc = 0.082, respectively). There was no significant difference between the phenotypic frequencies of HLA-DRB1 (17.3 vs 14.0 percent) and HLA-DQB1 alleles in responder and non-responder HCV patients. The HLA-DRB1*07 allele was significantly more common in HCV patients (33.3 vs 12.1 percent) than in controls (Pc = 0.0039), suggesting that the HLA-DRB1*07 allele is associated with chronic HCV infection.

Teoría de conjuntos aplicada a la caracterización matemática de unión de péptidos al HLA clase II / Set Theory Applied to the Mathematical Characterization of HLA Class II Binding Peptides

Las bases moleculares para el reconocimiento y la respuesta inmune están en la presentación de péptidos antigénicos. Se utilizaron la teoría de conjuntos y los datos experimentales para realizar una caracterización matemática de la región central de unión del péptido mediante la definición de 8 reglas asociadas a la unión al HLA clase II. Estas reglas se aplicaron a 4 péptidos promiscuos, 25 secuencias peptídicas naturales de la región central, de las cuales 13 presentaron unión, mientras que los demás no, y 19 péptidos sintéticos buscando diferenciar los péptidos. A excepción de uno, todos los péptidos de unión y no unión fueron caracterizados acertadamente. Esta metodología puede ser útil para escoger péptidos clave en el desarrollo de vacunas.

Antigen presentation contains the molecular basis for antigenic identification and immune responses. The set theory and experimental data were used in order to develop an union core region mathematic characterization through the definition of 8 laws associated to HLA class II binding. The laws were applied to 4 promiscuous peptides, 25 natural peptides sequences of core region: 13 binding peptides and 12 no binding peptides; and 19 synthetic peptides looking to differentiate peptides. Only one peptide was not rightly characterized. This methodology may be used to choose key peptides in the development of vaccine.

Alterations of HLA class I and II antigen expression in preinvasive, invasive and metastatic cervical cancers

HLA expression is altered in a large variety of human cancers. We performed immunohistochemical staining on tissues from normal, preinvasive, invasive and metastatic cervical cancer tissues using anti-HLA class I or class II antibody. In tissues from normal squamous epithelium, carcinoma in situ (CIS) and microinvasive carcinoma (MIC), the expressions of HLA-B, C heavy chains and class II heavy chain were significantly decreased as disease progressed. When the expression patterns were compared between primary and metastatic squamous cell carcinoma (SCC) lesions, statistically significant down-regulation of HLA class I and class II antigen in metastatic lesions was observed. The rates of HLA-B, C heavy chains and class II heavy chain expressions were all significantly down-regulated compared to the down-regulation rate of class I beta2-microglobulin (beta2m) in invasive squamous lesions, and the expressions of class II heavy chain in metastatic lesions was decreased further than that in primary lesions. Unlike SCC, the degree of HLA class I and class II loss was not evident as disease progressed in early stage of adenocarcinoma. In invasive adenocarcinoma lesions, only the expression of HLA-B, C heavy chains was decreased and no differences were seen in HLA-B, C heavy chain expression patterns between primary and metastatic lesions. These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in cervical cancer development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

Alterations of HLA Class I and II Antigen Expressions in Borderline, Invasive and Metastatic Ovarian Cancers / 대한암학회지

PURPOSE: The relationship between altered HLA expressions and ovarian carcinogenesis is not fully elucidated. MATERIALS AND METHODS: Histological evaluation comprised 20 serous adenocarcinoma, 5 borderline serous malignancy, 10 mucinous adenocarcinoma, 15 borderline mucinous malignancy. We used monoclonal antibodys to HLA class I beta2-microglobulin, class I B/C and class II heavy chain. RESULTS: There was no statistical difference in HLA expressions between borderline serous malignancy and normal ovarian tissue. In serous adenocarcinoma, beta2-microglobulin, B/C and class II heavy chain expressions were down-regulated. In metastatic cancer, B/C and class II ex pressions were also down-regulated. But the HLA expression of tumor or normal stromal tissue in primary tumor, were not down-regulated compared with the tissues in metastasis. In borderline mucinous malignancy, class II expressions were down-regulated. In mucinous adenocarcinoma, beta2-microglobulin, B/C and class II expressions were down-regulated. In metastatic ovarian cancer, B/C and class II expressions were down-regulated. But, in borderline malignancy, the result failed to reach statistical significance except class II of borderline mucinous malignancy. CONCLUSION: Loss of HLA class I and II molecules in invasive ovarian cancers raises the possibility that this could be a mechanism for tumor cells to have invasiveness.

Alterations of HLA Class I and II Antigen Expressions in Preinvasive, Invasive and Metastatic Cervical Cancers / 대한암학회지

PURPOSE: The relationship between altered HLA expressions and cervical carcinogenesis is not fully elucidated. MATERIALS AND METHODS: The histological evaluation comprised of 21 microinvasive squamous cell carcinoma (SCC), 26 invasive SCC, 3 microinvasive adenocarcinoma and 9 invasive adeno carcinoma of cervix. We used monoclonal antibodys (mAbs) to HLA class I beta2-microglobulin (L368), HLA class I B/C heavy chains (HC-10) and HLA class II heavy chain (LG II-612.14). RESULTS: In tissues from microinvasive SCC, the expressions of B/C heavy chains and class II heavy chain were significantly decreased. The expressions of beta2-microglobulin, B/C chains, and class II heavy chain in SCC were all significantly decreased. Especially, in the metastatic tissue from the same patient, the expressions of beta2-microglobulin and B/C chains showed to be somewhat decreased compared to those in primary tumor tissues, and the expression of class II heavy chain was decreased further than that in primary lesion. In primary invasive adenocarcinoma, the expression of B/C chains was significantly decreased. CONCLUSION: These results suggest that alterations of HLA class I and II expressions seem to occur at a particular step in tumor development and depend on tissue types: when the tumor becomes invasive and starts to metastasize.

HLA-DQA1, HLA-DQB1, HLA-DRB1 in Korean Patients with Pulmonary Tuberculosis-by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method / 감염

BACKGROUND: Pulmonary tuberculosis is affected by environmental factors, such as hygiene, nutrition, and socioeconomic status. Recently it has also been shown to be correlated with specific HLA types in foreign countries, although the mechanism underlying this association remains unknown. The aim of this study was to investigate the frequency and contribution of specific HLA alleles to pulmonary tuberculosis in Koreans. METHODS: HLA alleles of 97 patients whose illness was diagnosed as pulmonary tuberculosis by sputum acid-fast bacilli stain, culture, chest X-ray, and clinical evaluation at the Korean National Tuberculosis Association Department of Medical Operation were compared to those of 100 blood donors as controls. The polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method was used to define HLA-DQA1, HLA-DQB1, and HLA-DRB1 alleles. RESULTS: Among the patients analyzed by PCR- SSOP for HLA-DQA1 alleles, 63.9% were typed as HLA-DQA1*01, 50.5% HLA-DQA1*03, 22.6% HLA- DQA1*05, 8.2% HLA-DQA1*02, 7.2% HLA-DQA1* 06, and 4.1% HLA-DQA1*04. No difference in the distribution of HLA-DQA1 alleles between patients and healthy controls could be found, with the exception of HLA-DQA1*04, which was more common among controls. Regarding HLA-DQB1 alleles among the patients, 60% were typed as HLA-DQB1*03, 45% HLA-DQB1*06, 21.3% HLA-DQB1*04, 18.8% HLA- DQB1*05, and 11.3% HLA-DQB1*02. The allele distribution of HLA-DQB1 was not significantly different between patients and controls. For HLA-DRB1 alleles, 29.5% were typed as HLA-DRB1*02, 27.4% HLA- DRB1*08, 25.3% HLA-DRB1*04, 23.2% HLA-DRB1* 09, 20% HLA-DRB1*12, and 12.6% HLA-DRB1*13. There was also no difference between patients and controls in the allele distribution of HLA-DRB1. CONCLUSION: In Korea, where tuberculosis is relatively prevalent, pulmonary tuberculosis seems to be independent of HLA-DQA1, HLA-DQB1, and HLA- DRB1, although we found a statistically significant difference in HLA-DQA1*04 frequency between tuberculosis patients and controls.

HLA-DQA1, HLA-DQB1, HLA-DRB1 in Korean Patients with Pulmonary Tuberculosis-by the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method / 감염

BACKGROUND: Pulmonary tuberculosis is affected by environmental factors, such as hygiene, nutrition, and socioeconomic status. Recently it has also been shown to be correlated with specific HLA types in foreign countries, although the mechanism underlying this association remains unknown. The aim of this study was to investigate the frequency and contribution of specific HLA alleles to pulmonary tuberculosis in Koreans. METHODS: HLA alleles of 97 patients whose illness was diagnosed as pulmonary tuberculosis by sputum acid-fast bacilli stain, culture, chest X-ray, and clinical evaluation at the Korean National Tuberculosis Association Department of Medical Operation were compared to those of 100 blood donors as controls. The polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method was used to define HLA-DQA1, HLA-DQB1, and HLA-DRB1 alleles. RESULTS: Among the patients analyzed by PCR- SSOP for HLA-DQA1 alleles, 63.9% were typed as HLA-DQA1*01, 50.5% HLA-DQA1*03, 22.6% HLA- DQA1*05, 8.2% HLA-DQA1*02, 7.2% HLA-DQA1* 06, and 4.1% HLA-DQA1*04. No difference in the distribution of HLA-DQA1 alleles between patients and healthy controls could be found, with the exception of HLA-DQA1*04, which was more common among controls. Regarding HLA-DQB1 alleles among the patients, 60% were typed as HLA-DQB1*03, 45% HLA-DQB1*06, 21.3% HLA-DQB1*04, 18.8% HLA- DQB1*05, and 11.3% HLA-DQB1*02. The allele distribution of HLA-DQB1 was not significantly different between patients and controls. For HLA-DRB1 alleles, 29.5% were typed as HLA-DRB1*02, 27.4% HLA- DRB1*08, 25.3% HLA-DRB1*04, 23.2% HLA-DRB1* 09, 20% HLA-DRB1*12, and 12.6% HLA-DRB1*13. There was also no difference between patients and controls in the allele distribution of HLA-DRB1. CONCLUSION: In Korea, where tuberculosis is relatively prevalent, pulmonary tuberculosis seems to be independent of HLA-DQA1, HLA-DQB1, and HLA- DRB1, although we found a statistically significant difference in HLA-DQA1*04 frequency between tuberculosis patients and controls.

Cytokine Production by Peripheral Blood Mononuclear Cells in Renal Transplantation Rejection and Their Effect on Expressions of ICAM-1 and HLA Class II Antigen / 대한내과학회지

OBJECTIVES: We examined the levels of IL-1 , IL-6, TNF- , and IFN-gamma in peripheral blood mononuclear cells (PBMC) supernatants of kidney allograft recipients and also investigated the effect of PBMC supernatants on the expressions of HLA Class II antigen and ICAM-1 on endothelial cells. METHODS: PBMC were harvested before grafting, at steady state after grafting (serum creatinine < 2.0 mg/dL), at the onset of acute rejection episodes, and at steady state after rescue from acute rejection episodes. At each step, we examined the levels of cytokines in PBMC supernatants and investigated supernatants induced HLA class II antigen and ICAM-1 expression on cultured umbilical venous endothelial cells. RESULTS: HLA class II antigen and ICAM-1 expression were higher in endothelial cells stimulated with PBMC supernatants from uremic hemodialysis patients (N=10) than from control subjects (N=8). The levels of IL-1 , IL-6, TNF- , and IFN-gamma in PBMC supernatants were higher in uremic hemodialysis patients than in control subjects. In steady state after grafting, significant reductions in the PBMC supernatants induced HLA class II antigen and ICAM-1 expression on endothelial cells and the levels of these cytokines were found. In graft recipients who underwent rejection (N=5), cytokine production by PBMC and PBMC supernatants induced HLA class II antigen and ICAM-1 expression increased at the time of rejection and decreased after treatment of rejection but not significant. CONCLUSION: Cytokine production by PBMC and PBMC supernatants induced HLA class II antigen and ICAM-1 expression were higher in uremic hemodialysis patients than in normal controls. They significantly decrease in steady state after grafting and immunosuppressive therapy was considered as a major factor responsible for that. Further studies ,however, are still required to clarify the roles of cytokines, HLA class II antigen, and ICAM-1 in a series of allograft rejection process.

Surface Markers Expression in Pre-and Post-CD80(B7-l) Gene Transfected Human Tumor Cell Lines / 中国肿瘤生物治疗杂志

A crucial role in eliciting anti-tumor immunity of costimulatory molecule CD80(B7-1) has been demonstrated by animal experimental studies.In this paper, CD80 expression in human tumor cell lines and EBV-transformed B cell was detected using RT-PCR and FACS methods. The results showed that CD80 expression of Raji and EBV-transformed B cell was positive but that of 3AO,MCF-7,MDA-453,MKN-45, Hela was negative. We have constructed retroviral vector CD80-pLN,transfected package cell PA317, screened high titer rctrovirus supernatant then infected human tumor cell lines and gained CD80 positive tumor cell clones. With pre-and post-CD80-transfected human breast carcinoma cell line MDA-453,the upregulated expression of ICAM-I, HLA class I molecule was observed, but the expression of HLA class II molecule wasn't changed.