Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study

Background: Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims: The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods: Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results: Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4–25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7–31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4–10.3. Limitations: The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion: HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

Correlation between HLA-DQB1 and HLA-DRB1 gene polymorphisms and caries: a systematic review and Meta-analysis / 口腔疾病防治

Objective@#Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. @*Methods@# Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias.@*Results @# In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). @*Conclusion @#HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.

Asociación genética entre los Loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a padecer Lupus eritematoso sistemático / Genetic association between the Loci HLA-DRB1 and HLA-DQB1 with susceptibility to suffer from systemic lupus erythematosus

La investigación en Inmunogenética brinda información acerca de marcadores genéticos asociados con enfermedades autoinmunes, como el Lupus Eritematoso Sistémico (LES), se puede observar entonces ciertos factores de riesgo o protección hacia la enfermedad en una población determinada. OBJETIVO: Determinar la asociación genética entre los polimorfismos del Complejo Principal de Histocompatibilidad (CPH) representados por los loci HLA-DRB1 y HLA-DQB1 con la susceptibilidad a LES. METODOLOGÍA: Se trabajó con 85 pacientes lúpicos y 85 pacientes sin la enfermedad; se obtuvo DNA humano a partir de sangre periférica, se realizó un PCR-SSP de baja y alta resolución para tipificar molecularmente a los loci HLA-DRB1 y HLA-DQB1. Se determinó las frecuencias alélicas, las cuales fueron asociadas con ambas muestras mediante el uso del Odds Ratio, a un nivel de significancia del 5 %. RESULTADOS: Los resultados del PCR-SSP de baja resolución muestran que ningún alelo HLA tiene un rol predisponente, se observó que el alelo HLA-DRB1*04 presenta un rol protector OR=0,49 (p=0,03). Los resultados por PCR-SSP de alta resolución muestran que los alelos HLA-DRB1*03:01 (OR=18,3; p=0,007), DRB1*04:04 (OR=4,2; p=0,009), DRB1*09:01 (OR=18,3; p=0,007), HLA-QB1*03:03 (OR=18,8; p=0,006) y DQB1*02:01 (OR=21,2; p=0,003) son factores de riesgo. Se evidenció que los alelos HLA-DRB1*08:02 (OR=0,42; p=0,003) y HLA-DQB1*04:02 (OR=0,50; p=0,02) son de carácter protector. CONCLUSIONES: Los alelos que representan riesgo de padecer LES en la muestra estudiada son HLA-DRB1*03:01, 04:04, 09:01 y HLA-DQB1*03:03, 02:01. Los alelos que tiene un carácter protector a la enfermedad son HLA-DRB1*08:02 y HLA-DQB1*04:02.

Immunogenetics research provides information on genetic markers associated with autoimmune diseases such as systemic lupus erythematosus (SLE), you can then observe certain risk factors or protection to the disease in a given population. To determine the genetic association between polymorphisms of the Major istocompatibility Complex loci represented by the HLA-DRB1 and HLA-DQB1 with susceptibility to SLE. METHODOLOGY: We worked with 85 lupus patients and 85 patients without the disease; Human DNA was obtained from peripheral blood, PCR-SSP low and high resolution molecularly performed to establish the loci HLA-DRB1 and HLA-DQB1. Allele frequencies, which were associated with both samples using the Odds Ratio at a level of significance of 5% were determined. RESULTS: Results of PCR-SSP low-resolution HLA show that no predisposing allele plays a role, we observed that HLA-DRB1*04 allele has a protective role OR=0.49 (p=0.03). The PCR-SSP results of high resolution show that the HLA-DRB1*03:01 alleles (OR=18.3; p=0.007), DRB1*04:04 (OR=4.2; p=0.009), DRB1*09:01 (OR=18.3; p=0.007), HLA-QB1*03:03 (OR=18.8; p=0.006) and DQB1*02:01 (OR=21.2; p=0.003) are risk factors. We demonstrated that HLA-DRB1*08:02 alleles (OR=0.42; p=0.003) and HLA-QB1*04:02 (OR=0.50; p=0.02) are of a protective nature. CONCLUSIONS: The alleles representing LES risk in the study sample are HLA-DRB1*03:01, *04:04, *09:01 and HLA-DQB1*03:03, *02:01. The alleles having a protective character to the disease are HLADRB1* 08:02 and HLA-DQB1*04:02.

Relationship between HLA-DQB1 allele polymorphism with HPV16 infection and cervical cancer susceptibility in Guangxi Zhuang women / 中国免疫学杂志

Objective:To study the relationship of Guangxi Zhuang women being infected by HPV16 and suffering from cervical cancer with HLA-DQB1 allele polymorphism.Provide clues for seeking hereditary susceptibility gene or resistant gene of cervical cancer of Guangxi Zhuang women.Methods:Chose the cervical cancer diagnosed female patients and health women 171 cases respectively aged between 25 and 45 of Guangxi as subject investigated(people in the two groups were paired by age ±3 years).Took their samples to extract HPV DNA and human genome DNA.Then detected HLA-DQB1 alleles and HPV genetype applying PCR-SSP and molecular diversion hybrid technology.Finally the data were statistically analyzed.Results:(1)The total infection rate of HPV in 171 cases of cervical cancer patient was 91.22%,in which the high-risk virus accounted for 90.76%,HPV16 was the main pathogenic subtypes(43.58%).(2)The allele carrying rate of HLA-DQB1*04 in the cervical cancer group was higher than the health control group with statistically significant difference(P0.05).(3)The occurrence frequency of HLA-DQB1*04 alleles in HPV16 positive cervical cancer patients was significantly higher than HPV16 negative patients with statistically significant difference(P<0.05).Conclusion:HLA-DQB1*04 alleles are probably the susceptibility genes of cervical cancer of Guangxi Zhuang women;HLA-DQB1*06/09 alleles are probably the protective genes of cervical cancer of Guangxi zhuang women;HLA-DQB1*02/05/07/08 alleles seem irrelevant to hereditary susceptibility of cervical cancer of Guangxi Zhuang women.And Guangxi Zhuang women carried HLA-DQB1*04 alleles are more likely to infect HPV16 that increase the risk of cervical cancer.

Relationship between HLA-DQB1 allele as well as expression level of Th1/Th2 cytokines with familial clustering of hepatocellular carcinoma in Guangxi yao / 中国免疫学杂志

Objective:To elucidate the relationship between HLA-DQB1 allele polymorphism as well as the expression level of Th1/Th2 cytokines with familial clustering of hepatocellular carcinoma ( HCC) to provide some evidence for the seeking susceptibility gene or resistant gene of HCC in Guangxi yao,China.Methods:With the same sexuality,age ±5 year,40 members whose families have had two or more HCC patients( high-occurrence families) were selected as the case group,and 40 members whose families have no any cancer patient were selected as the controls.Peripheral blood samples were collected to extract DNA,PCR-SSP was used to detect HLA-DQB1 alleles and ELISA was used to detect IL-2,IL-4 and IL-10.Results:(1) The gene frequency of the HLA-DQB1*02/09 alleles in the case group was higher than that in the controls(P0.05 ).( 2 ) The gene frequency of alleles HLA-DQB1 in HBsAg positive group and HBsAg negative group were never significant difference (P>0.05).(3)The expression levels of IL-4,IL-10 in the case group was higher than that in the control ( P<0.05 ).( 4 ) The expression level of IL-10 in the positive group of the HLA-DQB1*02 allele was higher than that in the negative group of the HLA-DQB1*02 allele ( P<0.05 ).( 5 ) The expression level of IL-4 in the positive group of the HLA-DQB1*09 allele was higher than that in the negative group of the HLA-DQB1*09 allele( P<0.05) .Con-clusion:(1) HLA-DQB1*02/09 seem to be susceptibility genes of hepatocellular carcinoma in high HCC incidence areas of Guangxi yao.(2) There may be not significant correlation bewteen HLA-DQB1 alleles and the susceptibility of HBV infection in high HCC incidence areas of Guangxi yao.( 3 ) The imbalance of IL-4, IL-10 might be associated with familial clustering of hepatocellular carcinoma in Guangxi yao.(4)The imbalance of IL-10 might be due to the carrying of HLA-DQB1*02;the imbalance of IL-4 might be due to the carrying of HLA-DQB1*09.Through the same approaches,these might lead to the phenomenon of familial aggregation of HCC in Guangxiyao.

A study of the frequencies of HLA-DQA1 alleles and their clinical application values in the donor-recipient HLA-10/10 matched hematopoietic stem cell transplantation / 中华微生物学和免疫学杂志

Objective To analyze the frequencies of HLA-DQA1 alleles and their clinical values in the donor-recipient HLA-A,-B,-C,-DRB1,-DQB1 (10/10) matched hematopoietic stem cell transplantation (HSCT).Methods This study recruited 127 patients who received allogeneic HSCT and 127 unrelated donors.High-resolution (High Res) DNA typing for HLA-DQA1 alleles were performed on the 254 subjects by using sequence specific oligonucleotide probes (SSOP) and high resolution of sequence specific primer(High Res SSP).Results The DQA1 allele genotypes of 36 pairs of donor-recipient were directly identified by using SSOP.The ambiguous DQA1 allele genotypes of the rest 91 pairs were identified by using High Res SSP.Among the 127 pairs of donor-recipient,5 pairs were HLA-DQA1 alleles mismatched,while the others were all matched.No significant differences in the distribution of HLA-DQA1 alleles were observed between the donors and the recipients.Sixteen HLA-DQA1 alleles were detected in the 127 donors,which were DQA1 * 02 ∶ 01 (19.3％),DQA1* 01 ∶ 02(19.3％),DQA1 * 03 ∶ 02/03 (17.0％),DQA1 *01∶03 (9.8％),DQA1*06∶01(9.1％),DQA1*05∶ 01(7.1％),DQA1*05∶05(5.9％),DQA1*03∶01 (4.7％),DQA1*01 ∶04(2.4％),DQA1*01∶05(2.0％),DQA1*01∶01(1.2％),DQA1*05 ∶ 03(0.8％),DQA1 *05 ∶ 08(0.8％),DQA1*04 ∶ 01(0.4％),DQA1*05 ∶ 06(0.4％) from high to low frequency.Moreover,a new allele was detected in the patients.The haplotypes' frequencies and linkage disequilibrium(LD) analysis of HLA-DQA1 and HLA-DQB1 showed that the most common haplotype was DQA1 *02 ∶ 01-DQB1 *02 ∶ 02(16.1％),followed by DQA1 *03 ∶ 02/03-DQB1 *03 ∶ 03 (11.8％)and DQA1 *01 ∶ 03-DQB1 * 06 ∶ 01 (9.1％).Stronger LD were observed between DQA1 * 02 ∶ 01 and DQB1*02 ∶ 02,DQA1 *03 ∶ 02 and DQB1*03 ∶ 03,DQA1 *01 ∶ 03 and DQB1*06 ∶ 01,HLA-DQA1*06∶01 andDQB1*03 ∶ 01,DQA1*05 ∶ 01 and DQB1*02 ∶ 02(P＜0.001).Conclusion There was strong linkage disequilibrium between HLA-DQA1 and HLA-DQB1 genes.The polymorphism of HLA-DQA1 gene was less than that of HLA-DQB1 gene.No more guidance was provided to donor selection in unrelated donor-recipient HLA matched HSCT by adding HLA-DQA1 genotyping,but it might have clinical application values in HSCT with HLA Ⅱ locus mismatched donor and recipient.

Performance of LIFECODES HLA-DQB1 Typing Kit Using Luminex Platform in Koreans

Intermediate-resolution HLA-DQ typing has gained importance in organ transplantation recently. We evaluated the performance of the LIFECODES HLA-DQB1 typing kit (Immucor, USA) using sequence-specific oligonucleotide (SSO) probe and Luminex platform (Luminex Corp., USA) on 100 samples tested by sequence-based typing (SBT) using the AlleleSEQR HLA-DQB1 kit (Abbott Molecular, USA) in Korean individuals. No sample showed ambiguity in the assignment of 4-digit HLA-DQB1 allele with the LIFECODES HLA-DQB1 SSO typing kit, and the results were fully concordant with those of high-resolution typing of AlleleSEQR HLA-DQB1 SBT up to 4-digit level. Three samples required adjustment of false reactions (3/100, 3.0%): two samples with DQB1*03:03/*06:01 showed false-positive result in probe 253, and 1 sample with DQB1*04:02/*05:02 showed false-negative result in probe 217. We tested an additional sample with DQB1*03:03/*06:01, which showed same false-positivity in probe 253 and 2 samples with DQB1*04:02/*05:02, which showed no false reaction. The false reactions did not result in ambiguity or change in the HLA allele assignment. We could assign HLA-DQB1 alleles to 4 digit-level without ambiguity, with 100% concordance with the SBT results. Thus, LIFECODES HLA-DQB1 SSO typing kit showed good performance for intermediate-resolution HLA-DQB1 typing in clinical laboratory for organ transplantation in Koreans.

Research of HLA II Class DRB1, DQA1, DQB1 Genetic Markers in Patients with HIV Infection and AIDS.

Aims: To find out the most frequent associations of the HLA II class loci DRB1*, DQA1*, DQB1* with the HIV/AIDS infection. Place and Duration of Study: The study took place in The Laboratory of Clinical Immunology and Immunogenetics (LCII) of Riga Stradiņš University (RSU), Riga, Latvia, Riga Eastern Clinical University Hospital, “Infectology Centre of Latvia”, between May 1991 and December 2004. Original Research Article British Journal of Medicine & Medical Research, 4(17): 4482-4500, 2014 4483 Methodology: We analysed the medical documentation of 2500 patients and included 1180 (888 men, 292 women, 185 of them in AIDS phase) HIV infected patients. Genomic DNA was extracted from the blood with phenol-chloroform extraction method. Lowresolution HLA typing for HLA- DRB1*; DQB1*; DQA1* was performed by polymerise chain reaction (PCR) with amplification with sequence-specific primers (SSP). PCR products were separated on 3% agarose, the amplified bands were visualized, and the HLA-DRB1; DQA1; DQB1 type was deduced. Results: Genetic markers of immunologic alleles upon development of HIV infection – HLA-DRB1*03(17:01); 05(11:01); 07:01; HLA-DQA1*01:01; 02:01; 03:01; 06:01; HLADQB1* 03:02; 05:01; 03:03; 03:04, as well as resistance markers connected with slow development of HIV infection – HLA-DRB1*01:01; 04:01; 06(13:01); HLA-DQA1*01:03; 04:01; 05:01; HLA-DQB1*03:01; 03:03; 04:01-2; 06:01; 06:02-8 are located in different groups of patients. High risk markers in case of HIV infection development belonging to the following groups of alleles: HLA-DRB1*03(17:01), DRB1*05(11:01), DQA1*01:01; 03:01 un DQB1*05:01; 03:02, as well as three-loci haplotypes HLA-DRB1*03(17:01)/ DQB1*05:01/ DQA1*01:01; HLA-DRB1*05(11:01)/DQB1*03:01/ DQA1 *05:01; DRB1*01:01/DQB1*03:02/ DQA1*03:01 and DRB1*01:01/DQB1*05:01/DQA1*01:01 are determined. Resistance to HIV infection development forms in the following groups of alleles: HLA-DRB1*01:01; 06(13:01), HLA-DQB1* 03:01; 06:02-8; HLA-DQA1*01:02; 01:03, as well as in haplotypes HLA- DRB1*01:01/DQB1*06:02-8/DQA1*01:02;HLADRB1* 06(13:01)/DQB1*06:02-8/DQA1*01:02; HLADRB1* 01:01/DQB1*03:01/DQA1*01:02; and HLA-DRB1*06(13:01)/DQB1*06:02-8/ DQA1*01:02 in different groups of HIV/AIDS patients. Conclusion: The prevalence of genes DRB1; DQA1; DQB1 and DRB1-DQA-DQB1 combinations in the five groups of HIV infected patients have been established. Comparative analysis was performed also in the group of healthy donors (control group). The role of the main histocompatibility complex has been established, it enables marker functions and that can be used in the additional prognostic diagnostics in case of HIV infection. The obtained results testify that upon the identification of HIV genes it is possible to understand the molecular mechanisms in case of progression of AIDS syndrome complex; this possibly can be beneficial for the determination of the clinical results of infected patients.

Traditional biomarkers in narcolepsy: experience of a Brazilian sleep centre / Biomarcadores tradicionias em narcolepsia: experiência de um centro de sono brasileiro

This study was thought to characterized clinical and laboratory findings of a narcoleptic patients in an out patients unit at São Paulo, Brazil. METHOD: 28 patients underwent polysomnographic recordings (PSG) and Multiple Sleep Latency Test (MSLT) were analyzed according to standard criteria. The analysis of HLADQB1*0602 allele was performed by PCR. The Hypocretin-1 in cerebral spinal fluid (CSF) was measured using radioimmunoassay. Patients were divided in two groups according Hypocretin-1 level: Normal (N) - Hypocretin-1 higher than 110pg/ml and Lower (L) Hypocretin-1 lower than 110 pg/ml. RESULTS: Only 4 patients of the N group had cataplexy when compared with 14 members of the L group (p=0.0002). DISCUSSION: This results were comparable with other authors, confirming the utility of using specific biomarkers (HLA-DQB1*0602 allele and Hypocretin-1 CSF level) in narcolepsy with cataplexy. However, the HLADQB1*0602 allele and Hypocretin-1 level are insufficient to diagnose of narcolepsy without cataplexy.

Este estudo foi idealizado para avaliar as características clinicas e laboratoriais de uma população de narcolépticos atendidos num centro de referência na cidade de São Paulo (Brasil). MÉTODO: 28 pacientes realizaram polissonografia e teste de múltiplas latências do sono segundo critérios internacionais. O alelo HLADQB1*0602 foi identificado por PCR. A Hipocretina-1 no líquido cefalorradiano (LCR) foi mensurada por radioimunoensaio. Os pacientes foram divididos em 2 grupos conforme o nível de Hipocretina-1. Normal (N) - Hypocretin-1 >110pg/ml e baixa (B) - Hypocretina-1 <110pg/ml. RESULTADOS: Somente 4 pacientes do grupo N tinham cataplexia quando comparados com 14 pacientes do grupo B (p=0,0002). DISCUSSÃO: Estes resultados foram comparáveis com outros autores, confirmando a utilidade do uso de biomarcadores específicos (HLA-DQB1*0602 e nível da hipocretina-1 no LCR) em narcolepsia com cataplexia. Porém, o alelo HLADQB1*0602 e a dosagem da Hipocretina-1 são insuficientes para o diagnóstico da narcolepsia sem cataplexia.

Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population.

AIM: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. MATERIALS AND METHODS: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. RESULTS: The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. CONCLUSION: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region.

Prevalence of the HLA-DQB1*0602 allele in narcolepsy and idiopathic hypersomnia patients seen at a sleep disorders outpatient unit in São Paulo / Prevalência do alelo HLA-DQB1*0602 em pacientes com narcolepsia e hipersonolência idiopática atendidos em ambulatório de sonolência em São Paulo

OBJECTIVE: Narcolepsy (with and without cataplexy) and idiopathic hypersomnia, are disorders with common features but with different HLA-DQB1*0602 allele prevalence. The present study describes the prevalence of HLA-DQB1*0602 allele in narcoleptics with and without cataplexy and in patients with idiopathic hypersomnia. METHOD: Subjects comprised 68 patients who were diagnosed for narcolepsy or idiopathic hypersomnia and 23 healthy controls according to the International Classification of Sleep Disorders-2. Subjects comprised 43 patients with narcolepsy and cataplexy, 11 patients with narcolepsy but without cataplexy, 14 patients with idiopathic hypersomnia and 23 healthy controls. Genotyping of HLA-DQB1*0602 allele was performed for all subjects. RESULTS: The prevalence of the HLA-DQB1*0602 allele was increased in idiopathic hypersomnia and in narcoleptic patients with and without cataplexy when compared to healthy subjects (p = 0.04; p = 0.03 and p < 0.0001, respectively). CONCLUSIONS: This finding is in accordance with those of previous studies. The gold standard exam of narcolepsy with cataplexy is Hypocretin-1 dosage, but in patients without cataplexy and idiopathic hypersomnia, there are no specific diagnostic lab findings. The presence of the HLA-DQB1* 0602 allele may be important for the differential diagnosis of situations that resemble those sleep disorders such as secondary changes in sleep structure due to drugs' consumption.

OBJETIVO: Narcolepsia (com e sem cataplexia) e hipersonolência idiopática são transtornos com características clínicas comuns, mas com prevalências do alelo HLA-DQB1*0602 diferentes. Este estudo descreve a prevalência do alelo HLA-DQB1*0602 em pacientes narcolépticos com e sem cataplexia e em pacientes com hipersonolência idiopática. MÉTODO: A amostra consistiu de 68 pacientes com diagnóstico de narcolepsia ou hipersonolência idiopática e 23 controles saudáveis segundo o International Classification of Sleep Disorders-2. A amostra foi composta de 43 pacientes com narcolepsia e cataplexia, 11 pacientes com narcolepsia e sem cataplexia, 14 pacientes com hipersonolência idiopática e 23 controles saudáveis. A análise da presença do alelo HLA-DQ*0602 foi realizada em todos os sujeitos. RESULTADOS: A prevalência do alelo HLA-DQB1*0602 foi maior nos grupos de pacientes com hipersonolência idiopática e em pacientes narcolépticos com e sem cataplexia quando comparada com a dos sujeitos saudáveis (p = 0,04; p = 0,03 e p < 0,0001, respectivamente). CONCLUSÕES: Os resultados são compatíveis com o de estudos anteriores. O exame padrão-ouro para a confirmação da narcolepsia em pacientes com cataplexia é a dosagem de hipocretina, mas em pacientes sem cataplexia e hipersonolência idiopática não há testes laboratoriais específicos para o diagnóstico. A presença do alelo HLA-DQB1*0602 pode ser importante no diagnóstico diferencial de situações semelhantes a esses distúrbios do sono, como alterações secundárias na estrutura do sono causadas por consumo de drogas.

Influences of anxiety on humoral immune functions and the correlations with HLA-DQB1 / 中国免疫学杂志

Objective:To investigate the association between anxiety and the change of humoral immune functions and its correlation with HLA-DQB1 polymorphisms.Methods:Total 31 resident doctors were selected randomly and tested by State-Trait Anxiety Inventory(STAI).IgG,IgA,IgM,complement C3 and complement C4 were detected with BECKMAN array360 system;HLA-DQB1*02、*03、*04、*05 and*06 alleles were individually amplified by polymerase chain reaction(PCR)using exon2 group-specific primers.The correlation between immune function and HLA-DQB1 polgmorphisms were investigated.Results:Statistical analysis showed that there was positive correlation with State Anxiety (Ta) and complement C3,either Trait Anxiety (Tc) and complement C3.There was significant difference between HLA-DQB1*02 positive and negative in Ta (P＜0.05),while no difference in complement C3(P＞0.05).There was significant difference between HLA-DQB1*04 positive and negative in Ta and Tc(P＜0.05),while no difference in complement C3(P＞0.05).Conclusion:Anxiety could change some humoral immune functions and this is related with HLA-DQB1 polymorphism.

Análisis de la asociación de HLA DRB1-DQB1 y autoanticuerpos en familias con Síndrome Poliendocrino Autoinmune (APS) / An analysis of the relationship between HLA DRB1-DQB1 and autoantibodies, in families with autoinmune polyendocrine syndrome (APS)

El APS es la asociación de enfermedades endocrinas autoinmunes, con otros desórdenes autoinmunes no endocrinos, denominados componentes mayores y menores. Este síndrome se clasificó en 4 tipos. Las alteraciones de la respuesta inmune provocan fallas regulatorias de la misma; y polimorfismos de HLA, entre otros, sumado a factores adquiridos o permanentes, representan gatillos disparadores de la autoinmunidad. Nuestro objetivo fue buscar la asociación de HLA-DRB1*-DQB1* en individuos pertenecientes a dos familias, con diagnóstico en uno o más de ellos de APS, o con enfermedades autoinmunes aisladas. Determinar los anticuerpos séricos: a21-OH, aGAD y aTPO y observar la asociación con el haplotipo HLA. Estudiamos padres e hijos de dos familias, dos integrantes padecían APS tipo 2 y 3; y otros con enfermedades autoinmunes. Buscamos HLA-DRB1*-DQB1* y cuantificamos a21-OH, aTPO y aGAD. Los pacientes con APS 2 y 3 presentaron el HLA-DRB1*0301-DQB1*0201. De los individuos estudiados, 5/9 tenían este haplotipo HLA y al menos un autoanticuerpo positivo. Hallamos el factor genético en 2/3 de los integrantes con enfermedades autoinmunes correspondientes a componentes mayores. La relación observada, entre APS y HLA-DRB1*0301-DQB1*0201, aumenta la posibilidad de identificar personas en riesgo de contraer afecciones autoinmunes en grupos familiares, en los cuales algún integrante padece APS.

The APS is the association of autoimmune endocrine diseases, with other non-endocrine autoimmune disorders, named mayor and minor components. This syndrome was classified in 4 types. The alterations of the immune response cause regulatory faults; and HLA polymorphisms, among others; taken in conjunction with acquired or permanent factors, these represent triggers of autoimmunity. Our objective was to find out the association of HLA-DRB1*-DQB1* in individuals belonging to two families, with diagnosis in at least one of them APS, or with isolated autoimmune diseases. To determine serum antibodies: a21-OH, aGAD and aTPO and to observe the association with HLA haplotype. We have studied parents and offspring of two families, two members who suffered APS type 2 and 3, and others with autoimmune diseases. We have looked for HLA-DRB1*-DQB1* and quantified a21-OH, aTPO and aGAD. Patients with APS 2 and 3 showed HLA-DRB1*0301-DQB1*0201. Among the population we have studied, 5/9 had this HLA haplotype and at least one positive auto antibody. We have found the genetic factor in 2/3 of the members with autoimmune diseases corresponding to greater components. The observed relation between APS and HLA-DRB1*0301-DQB1*0201, increases the possibility of identifying people at risk of catching autoimmune affections in familiar groups in which at least one member suffers APS.

Human Leukocyte Antigen Class II Association with Spontaneous Recovery from Hepatitis B Virus Infection in Koreans: Analysis at the Haplotype Level

It has been speculated that human leukocyte antigen (HLA) alleles are associated with the outcome of hepatitis B virus (HBV) infection although the data obtained from various populations have shown some inconsistencies. A total of 464 HBVinfected Korean individuals (80 spontaneously recovered [SR] and 384 chronically infected [CI]) were selected to investigate the association of HLA class II alleles with the viral clearance and persistence. Our results showed that: 1) multiple HLA class II alleles and haplotypes were associated with viral clearance (DRB1*1302, DRB1*1502, DQB1*0302, DQB1*0609, and related-haplotypes) and persistence (DRB1*0701, DQB1*0301, and related-haplotypes); 2) DRB1*1302 and DQB1* 0609 were more strongly associated with viral clearance. And the association of DQB1*0609 (pc=0.0084; OR, 7.24) with vial clearance was much stronger than previously recognized, DRB1*1302 (pc=0.0038; OR, 4.34); and 3) linkage to a specific DPB1 allele in a haplotype strengthened the association with viral clearance, although DPB1 itself was not associated with the outcome. These results indicate the existence of multiple factors controlling viral clearance in the HLA class II gene region. Further extended investigation on the genetic factors related to the outcome of HBV infection will provide valuable insights into the understanding of the mechanisms involved.

Prevalence of HLA DQB1*0602 allele in patients with migraine

BACKGROUND: Studies have shown a high prevalence of migraine among narcoleptic patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual aura has raised greater awareness of the genetic background in migraine. PURPOSE: Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of migraine. METHOD: We analyzed the presence of HLA DQB1*0602 allele in 50 healthy subjects with no history of migraine, 53 patients with migraine without aura and 52 patients with migraine with aura. RESULTS: There was no difference in the frequency of HLA DQB1*0602 allele when control subjects and all patients were compared. We failed to note any difference in frequencies when comparing migraine patients with and without aura. CONCLUSION: Further studies with different patient populations, with other hypothalamic markers (melatonin, hypocretin) in migraine patients may shed light on to its pathophysiology.

CONTEXTO: Estudos têm demonstrado o aumento da prevalência de enxaqueca em pacientes com narcolepsia, um distúrbio de sono associado a um gene do sistema HLA, o alelo HLA-DQB1*0602. As regiões DQ e DR do HLA estão em alto desequilíbrio de ligação e já foi descrito um aumento da freqüência do alelo HLA DRB1 em pacientes com enxaqueca com aura visual, o que fortalece uma hipótese de herança genética para a enxaqueca. OBJETIVO: Nossa hipótese é que o alelo HLA-DQB1*0602 pode estar relacionado com a fisiopatologia da enxaqueca destes pacientes. MÉTODO: Nós analisamos a presença do alelo HLA-DQB1*0602 em 50 voluntários sadios sem história de enxaqueca, 53 pacientes com enxaqueca sem aura e 52 pacientes com aura. RESULTADOS: Não houve diferença entre os controles sadios e os pacientes com enxaqueca. Não houve diferença entre os pacientes com enxaqueca com e sem aura. CONCLUSÃO: Futuros estudos com diferentes populações, com outros marcadores (melatonina e hipocretina) em pacientes com enxaqueca devem ser realizados para melhor esclarecimento de fisiopatologia.

Comparison of Narcolepsy with Cataplexy and without Cataplexy: Clinical Variables, HLA-DQB1*0602, and Hypocretin / 신경정신의학

OBJECTIVES: Narcolepsy is a sleep disorder, characterized by excessive daytime sleepiness, cataplexy, sleep paralysis and hypnagogic hallucination. Among these symptoms, cataplexy is one of the most pathognomonic symptoms in narcolepsy. This study was designed to investigate the clinical features, frequency of DQB1*0602 and CSF hypocretin levels in Korean narcoleptics with cataplexy to compare with those who have not cataplexy. METHODS: From August 2003 to July 2005, we selected 72 patients who have narcolepsy confirmed by nocturnal polysomnography and multiple sleep latency test (MSLT) as well as their history and clinical symptoms at Sleep Disorders Clinic of St. Vincent's Hospital, Catholic University of Korea. Patients were divided into 56 cataplexy-positive group (narcolepsy with cataplexy group) and 12 cataplexy-negative group (narcolepsy without cataplexy group). HLA typing was done in all patients for the presence of DQB1*0602, and patients received spinal tapping to measure the level of CSF hypocretin. Clinical variables were examined by semi-structured interview for narcolepsy patients. RESULTS: 1) In cataplexy-positive group, compared with cataplexy-negative group, the frequency of HLA-DQB1*0602 was found to be significantly increased (50 subjects, 89.3% vs. 8 subjects, 50.0%)(p=0.000). 2) In 48 out of 56 cataplexy-positive patients (85.7%), hypocretin levels were decreased (< or =110 pg/ml) or were below the detection limit of assay (<40 pg/ml). However, only 6 out of 16 cataplexy-negative patients (37.5%) exhibited decreased hyopcretin level. The difference between two groups were statistically significant (p=0.000). 3) Cataplexy-positive group, compared to cataplexy-negative group, reported more frequent hypnagogic hallucinations (36 subjects, 64.3% vs. 4 subjects, 25.0%)(p=0.005). However, there were no significant differences in frequency or severity of daytime sleepiness, sleep paralysis and demographic data. 4. In nocturnal polysomnography and MSLT findings, there were no significant differences in all sleep parameters between two groups. CONCLUSION: Higher frequency of HLA-DQB1*0602, and lower hypocretin levels in cataplexy-positive groups than catapelxy-negatives suggest that narcoleptics with cataplexy might be a etiologically different disease entity from narcoleptics without cataplexy. Additionally, Current criteria prevail for the diagnosis of narcolepsy need to be reclassified according to the presence of cataplexy or not.

Analysis of the markers related with relapse after withdrawal of antithyroid drug in patients with Graves' disease / 대한내과학회지

BACKGROUND: Graves' disease is an organ-specific autoimmune disease that is characterized by thyrotoxicosis, and this is caused by TSH receptor stimulating autoantibody. Antithyroid drugs have been a mainstay of treatment for Graves' patients. Unfortunately, over 50% of patients relapse after their first antithyroid drug treatment and the likelihood of remission cannot be foreseen. Some HLA genes are associated with disease susceptibility, but the association between HLA genes and relapse after drug withdrawal is unclear. In this study, we investigated the association between the HLA genes and the clinical parameters for predicting the clinical outcome of Graves' disease patients. METHODS: We enrolled the patients (n=191) with Graves' disease who were treated by antithyroid drug and who had previously undergone studies for their genetic susceptibility (HLA-DQB1, -DRB1). The success group included patients who maintained a euthyroid state for at least 12 months after withdrawal of drugs. The failure group was defined as the patients who relapsed within 1 year after discontinuation of drug or who could not discontinue their antithyroid drug treatment within 24 months. RESULTS: The rate of treatment failure was 75.4%. There was no significant association between the clinical outcome and the HLA genotyping. The genes that were associated with susceptibility to Graves' disease showed no association with the outcome. A few clinical parameters, such as male patients, severe thyrotoxicosis and high TSH-binding inhibitory immunoglobulin value were related to treatment failure. CONCLUSIONS: Genetic markers such as HLA-DQB1 and DRB1 can not be used, instead of the clinical parameters, to predict relapse after drug withdrawal.

HLA-DQB1 gene polymorphisms in Guangdong province detected by genechip / 第三军医大学学报

*0603.Conclusion The GF data of Chinese in Southern China are useful to correlation of diseases and anthropologic research.

Distribution of HLA-DQA1*01, *03, *05 and DQB1*02 Subtypes and the Associated Haplotypes in the Korean Population

BACKGROUND: As all HLA class II genes, the DQ genes show their polymorphic variation mainly in the second exon, which encodes the first extracellular domain of the molecule. PCR-SSOP (Polymerase chain reaction-Sequence specific oligonucleotide probe) techniques were frequently used for HLA-DQA1 and DQB1 typing but certain alleles, DQA1*0101/0104/0105, *0302/0303, *0501/0505 and DQB1*0201/*0202, which differ from each other in segment other than exon 2, could not be unequivocally assigned. METHODS: To overcome this problem, we applied additional PCR-SSP (PCR-Sequence specific primer) method to analyze DQA1 exons 1, 3 and 4 and DQB1 exon 3. And we investigated the distributions and haplotypes of HLA-DRB1, DQA1 and DQB1 alleles in 406 unrelated Korean healthy individuals. RESULTS: Using this method the indistinguishable alleles of DQA1 and DQB1 in PCR-SSOP were typed definitively. We also found several important associations between DQA1 and DQB1 alleles in the Korean population; DQA1*0101-DQB1*0501, DQA1*0104-DQB1*0502 or -*0503, DQA1 *0105-DQB1*0501, DQA1*0302-DQB1*0303, DQA1*0303-DQB1*0401 or -*0402, DQA1 *0501-DQB1*0201, DQA1*0505-DQB1*0301, and DQA1*0201-DQB1*0202. The haplotypes of DRB1-DQA1-DQB1 associated with DQA1*01, *03, *05, and DQB1*02 subtypes were investigated. Several haplotypes associated with these alleles were observed in the Korean population. CONCLUSION: Our results can be helpful to find potential unrelated donors for bone marrow registries and study the HLA-associated disease and anthropology at high-resolution allelic level.

Polymorphisms of HLA-DRB1 and -DQB1 Genes in Korean Patients with Pulmonary Tuberculosis / 결핵

BACKGROUND: It is well known that only 10% of those infected with Mycobacterium tuberculosis actually develop clinical disease, indicating the existence of host genetic factors regulating disease expression. In this study, we investigated HLA-DRB1 and -DQB1 gene polymorphisms in Korean patients with pulmonary tuberculosis (PTB). METHODS: HLA-DRB1 and -DQB1 gene polymorphisms were investigated in 67 PTB patients without previous treatment history, 38 drug-sensitive (DS) and 29 multidrug-resistant (MDR) cases, and 200 healthy controls. HLA-DRB1 typing was done using reverse SSO (sequence specific oligonucleotide) and PCR-SSCP (single strand conformational polymorphism) methods and DQB1 typing was done using PCR-RFLP (restriction fragment length polymorphism), PCR-SSCP and PCR-SSP (sequence specific primer) methods. RESULTS: Among the PTB patients, MDR-TB cases showed frequencies of DRB1*0701 and *08032 increased by about two-fold compared to those of normal controls, and likewise for their associated DQB1 alleles, DQB1*0202 and *0601 (15.5% vs. 34.5%, p=0.01). The frequency of HLA-DQB1*0609 was significantly increased in PTB patients (4.0% vs. 14.9%, p=0.004), showing similar increases in both DS and MDR cases. There was also an association of HLA alleles with the clinical severity of the disease according to the extent of lung lesion. Significantly increased frequencies of DRB1*08032 (4.2% vs. 32.6%, p=0.007) and DQB1*0601 (12.5% vs. 34.9%, p=0.047) were observed in more advanced (moderately & far advanced/DS and far advanced/MDR), compared with less advanced (minimal/DS and moderately advanced/MDR) lung lesions. Although DRB1*0701, DQB1*0202 and DQB1*0609 showed significant increases in different subsets of the disease, these HLA alleles did not show consistent association with disease severity. CONCLUSION: HLA-DRB1*08032 and DQB1*0601 alleles were associated with genetic susceptibility to MDR-TB in Korean patients, and also with disease severity and progression of PTB.