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• HLA genes are the most relevant genetic component for SLE disease risk and autoantibodies formation. • DRB1*03 allele was significantly associated with anti-SSA and anti-SSB antibodies production. • DRB1*16 genotypes either homozygote or heterozygote were positively associated with ANA and anti-Sm. • Dominant role of DRB1 over DQB1 alleles was observed for disease predisposition. One of the most relevant genetic components in systemic lupus erythematosus (SLE) is human leukocyte antigen (HLA) gene complex which plays a central role in autoimmune responses. This study aimed to explore the associations of HLA-DRB1/-DQB1 alleles and haplotypes with SLE risk and the appearance of autoantibodies in SLE disease. A total of 127 SLE patients and 153 ethnically matched healthy controls were enrolled. HLA-DRB1 and HLA-DQB1 alleles were determined by PCR-SSP method and then HLA alleles and haplotypes frequencies were compared between two groups and among the patients in terms of autoantibodies spectrum. We found that HLA-DRB1*03 and HLA-DRB1*16 alleles were significantly associated with increased risk (P = 0.008, P C =0.05 and P = 0.002, P C =0.02 respectively) and DRB1*01 conferred a potential protective role for disease (P = 0.03, P C =0.13). Similar associations were observed at haplotype level; DRB1*03~DQB1*02 (OR1.91, P = 0.01, P C =0.08), DRB1*16~DQB1*05 (OR3.65, P = 0.004,P C =0.06) and DRB1*01~DQB1*05 (OR0.36, P = 0.04, P C =0.22). Remarkably, we observed significantly associations of DRB1*03 with the appearance of anti-SSA/Ro (P C =0.02), anti-SSB/La (P C =0.002) and anti-coagulant (P = 0.007), DRB1*15 with anti-SSA/Ro (P C =0.04), DRB1*16 with anti-Sm (P C =0.02), DRB1*04 with anti-β2gpI (P C =3 * 10−5), anti-cardiolipin (P = 0.002) and rheumatoid factor (P = 0.004) and DRB1*13 with anti-Sm (P C =0.02) and anti-β2gpI (P C =0.01) antibodies. Also, negative associations of DRB1*04 with anti-Sm, anti-SSA/Ro, DQB1*03 with anti-Sm and DRB1*11 with anti-Sm and anti-β2gpI were observed. We identified DRB1*03 and DRB1*16 as risk alleles and DRB1*01 as a potential protective allele for SLE disease. More importantly, we found a close link between genetic susceptibility for SLE and autoantibodies status that was more evident for DRB1*03 allele. [ABSTRACT FROM AUTHOR]

HLA-DMB allele frequencies and HLA-DBM-DRB1-DQB1 extended haplotypes were studied for the first time in Amerindians (Cuenca city area, Ecuador). It was found that most common extended haplotypes gathered the most frequent HLA-DRB1 Amerindian alleles. HLA-DMB polymorphism studies may be important to uncover HLA and diseases pathogenesis and also in an extended HLA haplotype frameshift. HLA-DM molecule has a crucial role together with CLIP protein in HLA class II peptide presentation. HLA extended haplotypes including complement and non classical genes alleles are proposed to HLA and disease studies. [ABSTRACT FROM AUTHOR]

Background: Accurate pre-transplant prediction of late graft function remains an unmet need in kidney transplantation. The aim of this study was to evaluate HLA genes expression levels in pre-implantation biopsies (PIB) of deceased donor kidneys as markers for long-term graft outcome. Methods: HLA genes expression analysis was initially performed using microarray data of 53 PIB, previously generated by our laboratory. The validation analysis was performed by real-time PCR in 116 PIB from an independent cohort. Results: The microarray data showed association between high expression levels of HLA class II genes, especially HLA-DQB1 and -DQB2, in kidneys from young (18 to 49-year-old) donors and poor (eGFR < 45 mL/min/1.73 m 2 ) 1- and 5-year graft function. A subsequent study in an independent cohort, in which only HLA-DQB2 expression was evaluated, validated the association between increased HLA-DQB2 expression in PIB of kidneys from young donors and poor 1-year graft function: expression levels ≥0.0025 relative units conferred an odds ratio of 22.5, with positive and negative predictive values of 71.4% and 90.0%, respectively. Conclusion: Heightened expression of HLA-DQB1 and -DQB2 in PIB are promising tools for pre-transplant risk assessment of poor late graft function in transplants with kidneys from 18 to 49-year-old donors. [ABSTRACT FROM AUTHOR]

• The present study investigated HLA-DQB1 polymorphisms in three generations (Grandmother, mother and offspring) of patients with hepatitis B in their families. • The typing of HLA-DQB1 showed that HLA-DQB1*04:01 has the most frequent allele in patients with chronic hepatitis B is considered a risk factor for susceptibility to hepatitis B infection. • HLA-DQB1*06:04 that was observed only in one case in the control group, was suggesting a protective role in HBV infection and spontaneous clearance of the virus. • HLA-DQB1*03:03 was reported in recovered and healthy groups was correlated with viral clearance and suppression of CHB formation. • HLA-DQB1*05:02 is a polymorphism associated with a higher risk of liver cirrhosis; it was observed in three-generation, two-generation, and intra-familial groups, as well as in one healthy subject in fifth group. • HLA-DQB1*05 that associated with increased susceptibility to HBV infection, its persistence, and the development of CHB, was the most common HLA allele in three generations, two generations, and other groups. The presence of polymorphisms in the human leukocyte antigen (HLA)-DQB1 gene, along with its expression, has been demonstrated to be correlated with spontaneous clearance and susceptibility to HBV infection. The present study aimed to evaluate the possible role of genetic polymorphisms in HLA-DQB1 in three generations of patients with chronic hepatitis B (CHB). Based on the inclusion criteria, 90 CHB patients, 18 individuals recovered from HBV infection, and 40 healthy subjects were chosen. The DNA contents of the whole blood samples were extracted in order to perform HLA-DQB1 typing by the PCR technique. Besides whole blood samples, sera were applied to measure liver function tests (LFTs), as well as the titers of anti-HDV and anti-HCV. Also, in all CHB patients were measured liver stiffness (LSM) by Fibro Scan. The results of HLA-DQB1 polymorphisms (rs2856718 and rs7453920) demonstrated that the majority of polymorphisms in CHB patients were HLA-DQB1*03, HLA-DQB1*05, HLA-DQB1*04:01 and HLA-DQB1*03:01 that associated with HBV persistence and chronicity. Among the patients who showed these polymorphisms, the mean±SD, LSM was 4±1.57 KPa and most of them, F grade was reported as F2, which was a sign of disease progression towards chronicity. HLA polymorphisms imputation revealed that HLA-DQB1*06:04 (3.4%, P-Value = 0.2) was detected only in healthy subjects as protective polymorphism, while the allele HLA-DQB1*03:03 was reported in both healthy subjects (P-Value = 0.06) and recovered patients (P-Value = 0.1) as suppressor of CHB formation. The allele HLA-DQB1*05:02 was found in both healthy subjects (3.4%) and CHB patients (4.5%) which was associated with risk to liver cirrhosis (P-Value = 0, OR: 0.002 0.95CI: 0.000-0.15). HLA polymorphism analysis indicated that 17.39% of patients who were seropositive for anti-HCV carried the HLA-DQB1*03:01. HBV resistance or infection risk could be assessed by DBQ1 typing. The existence of polymorphisms in HLA gene could influence the clearance (HLA-DQB1*03:03) or susceptibility and persistence of infection (HLA-DQB1*03, HLA-DQB1*05, HLA-DQB1*04:01 and HLA-DQB1*03:01). These results have the potential to improve personalized therapy and prognosis for HBV infection. [ABSTRACT FROM AUTHOR]

Background Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Study design Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT–HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p -value was calculated using multiple logistic regression. Results While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 ( p = 0.02), -DQ3 ( p = 0.02) and -DQ5 ( p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 ( p = 0.01) and HLA-DQ5/5 ( p = 0.03) combinations constitute additional predictor of protective status. Conclusion Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies. [ABSTRACT FROM AUTHOR]

Human leukocyte antigens (HLA) alleles may affect the development of cervical cancer through immunologic control of human papillomavirus (HPV). The association between HLA-DQB1 alleles and risk of cervical cancer has been extensively studied, but the results obtained remain inconsistent. To explore a more extensive role of HLA-DQB1 alleles on cervical cancer risk, we carried out a meta-analysis including 4862 cases and 8988 controls from 22 published studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The overall results suggested that HLA-DQB1 *02 (OR = 0.91, 95% CI = 0.82–0.99), *03 (OR = 0.85, 95% CI = 0.74–0.97) and *0603 (OR = 0.62, 95% CI = 0.53–0.72) had a significantly association with decreased cervical cancer risk. In contrast, DQB1 *05 (OR = 1.18, 95% CI = 1.01–1.38), *0301 (OR = 1.14, 95% CI = 1.06–1.23) and *0402 (OR = 1.31, 95% CI = 1.04–1.64) conferred a significantly higher risk to cervical cancer. Moreover, a significantly association with increased or decreased cervical cancer risk was found among Europeans and Asians after stratification of the HLA-DQB1 alleles by ethnicity. These findings supported that the HLA-DQB1 alleles may contribute to genetic susceptibility of cervical cancer. Further studies with a greater number of cases are expected to confirm our results. [ABSTRACT FROM AUTHOR]

Aim of the work This study was conducted to compare the HLA-DQB1∗06 allele frequency among Egyptian SLE patients and controls. The association of that allele with clinical features and distinct autoantibody profiles in SLE patients was also assessed. Patients and methods This study included 48 consecutive Egyptian SLE patients and 49 age and sex matched unrelated healthy Egyptian subjects as a control group. All patients underwent full history taking, thorough clinical examination, SLE cumulative organ damage was scored using the Systemic Lupus International Collaborating Clinics (SLICC) damage index. Routine laboratory investigations were done as well Genomic DNA amplification by polymerase chain reaction with sequence-specific primers technique (PCR-SSP) to detect HLA DQB1∗6. Results HLA-DQB1∗06 was significantly more frequent among the SLE patients. Our results showed HLA-DQB1∗06 to be associated with SLE (39.6% in patients and 8.2% in controls, OR = 7.23; 95% CI = 2.22–23.6; P = .00). We found no association with the clinical findings or antibodies found in our patients apart from a significant negative association with vasculitis. Conclusion The current work suggests that DQB1∗06 allele is a susceptibility allele in Egyptian patients with SLE but is not related to the clinical presentation or laboratory tests of SLE. To our knowledge this is the first study of the frequency of DQB1∗06 alleles in Egyptian SLE patients. [ABSTRACT FROM AUTHOR]

Highlights: [•] Specific HLA class II alleles (DRB1/DQB1) were related to antibody response to HepB. [•] DRB1*1301and DRB1*0602 had high specificity but low sensitivity. [•] An assessment of study quality was conducted, which was absent in similar analysis. [•] Sample collection of non-responders is difficult. The meta-analysis was necessary. [ABSTRACT FROM AUTHOR]

Abstract: Background: Previous studies reported an association between the human leukocyte antigen (HLA)-DQ antigen beta 1 chain (DQB1) alleles and dilated cardiomyopathy (DCM). However, the results of those studies have been inconsistent. To clarify the association between HLA-DQB1 and DCM, we performed a systematic review and meta-analysis of case-control studies. Methods: Searches were performed using the PubMed database, the Excerpta Medica Database (EMBASE), the Cochrane Central Register of Controlled Trials database, the Science Citation Index database, the China Biology Medicine disc, the China National Knowledge Information database, the Wanfang database, and the Chinese Scientific and Technological Journal Database (VIP database). The search terms included “dilated cardiomyopathy” and “DQB1.” Ten case-controlled studies were included in the systematic review to assess the association between DCM and the HLA-DQB1∗0201, ∗0302, ∗0504, ∗0301, and ∗0602 alleles. Results: In total, 8 studies were included in the meta-analysis of the HLA-DQB1 ∗0201 allele. The pooled odds risk (OR) for this allele was .47, with a 95% confidence interval (CI) of .28 to .77 (P < .01). With respect to the HLA-DQB1 ∗0504 allele, only 3 studies were included in our meta-analysis. The pooled OR was .36 (95% CI, .15 to .84; P < .05). Nine, 8, and 7 studies of the HLA-DQB1 ∗0301, ∗0302, and ∗0602 alleles, respectively, were included in our meta-analysis. No statistically significant difference was evident in the frequency of these 3 alleles between the DCM and normal control groups. Conclusion: The HLA-DQB1 ∗0201 and ∗0504 alleles may be protective against DCM. [Copyright &y& Elsevier]

Abstract: Objective: Our aim was to investigate the correlation between onset age, clinical features and HLA-DQA1/DQB1 genetic variability in myasthenia gravis (MG) patients in Southern Han Chinese. Methods: 205 MG patients and 100 controls were genotyped for HLA-DQA1 and -DQB1 using sequence-based typing (SBT) and analyzed for haplotype frequencies. Anti-acetylcholine receptor (AChR) autoantibodies were measured in all, and muscle-specific tyrosine kinase (MuSK) antibodies were tested in AChR antibody negative patients. Results: HLA-DQA1/DQB1 haplotypes showed association only with childhood-onset MG. Haplotype DQA1*03:02/DQB1*03:03:02 (DQ9) was positively associated with the childhood-onset MG, while haplotype DQA1*02:01/DQB1*02:02 and DQA1*05:01:01/DQB1*02:01:01 (DQ2) were negatively associated with this group. Childhood-onset ocular MG patients had an extremely high phenotype frequency of DQ9 haplotype (90.1% of patients, 34.0% of controls, p ≤0.0001, OR=17.8). Conclusions: The childhood-onset ocular MG in Southern Han Chinese may present a particular subgroup of distinct genetic background. Its correlation to the HLA haplotype DQA1*03:02/DQB1*03:03:02 might explain the phenotypic difference of MG between Han Chinese and Caucasians. [Copyright &y& Elsevier]

Summary: Background: Some studies have suggested that human HLA status might potentiate development of keloids phenotype, and exists ethnic differences. No report has been published about HLA-DQA1 and DQB1 alleles associated with keloids in Chinese Hans. Objectives: To investigate whether HLA-DQA1 and DQB1 alleles are associated with genetic susceptibility to keloids in Chinese Hans. Methods: Polymerase chain reaction-sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles among 192 patients with keloids and 273 healthy controls in Chinese Hans. Results: (1) The frequencies of HLA-DQA1*0104, DQB1*0501 and DQB1*0503 (OR=2.13, P c =0.0063; OR=14.42, P c <10−7 and OR=6.09, P c <10−7, respectively) were significantly higher, while the frequencies of DQA1*0501, DQB1*0201 and DQB1*0402 (OR=0.46, P c =0.0099; OR=0.24, P c <10−4 and OR=0.10, P c =0.0054, respectively) were lower in patients than in controls. (2) In this study significant susceptibility haplotypes to keloids were DQA1*0104–DQB1*0501 and DQA1*0104–DQB1*0503. (3) HLA-DQB1*0501 and DQB1*0503 were positively associated with all subgroups of keloid patients. However, the DQA1*0104 (OR=2.51, P c =0.0009; OR=2.22, P c =0.0090 and OR=2.20, P c =0.0117, respectively) was only prevalent in keloid patients with single site, moderate severity and negative family history. (4) HLA-DQB1*0201 (OR=0.27, P c =0.0018 and OR=0.27, P c =0.0012, respectively) and DQB1*0402 (OR=0.07, P c =0.0270 and OR=0.07, P c =0.0306, respectively) were negatively associated with moderate severity and negative family history in keloids, moreover, HLA-DQB1*0201 (OR=0.23, P c =0.0003) and DQA1*0501 (OR=0.43, P c =0.0234) were less prevalent in patients with single site. Conclusion: This study demonstrated the positive association of HLA-DQA1 and DQB1 alleles and haplotypes with keloids. [Copyright &y& Elsevier]

Abstract: We made an attempt to find out whether Human Leucocyte Antigen (HLA)-DQB1 and -DPB1 alleles are associated with susceptibility or resistance to Human Immunodeficiency Virus (HIV) infection and development of pulmonary tuberculosis (PTB) in HIV infected patients. The allelic profile of HLA-DQB1 and -DPB1 was studied among HIV patients without pulmonary tuberculosis (HIV+PTB−) (n =115), HIV patients with pulmonary TB (HIV+PTB+) (n =59), HIV negative PTB patients (HIV−PTB+) (n =110) and healthy controls (n =112) by polymerase chain reaction and sequence specific oligonucleotide probe method. Increased frequency of HLA-DQB1*050301 was observed in HIV+PTB− [p =0.024, Odds Ratio (OR) 2.30, 95% Confidence Interval (CI) 1.11–4.90] and HIV+PTB+ patients (p =0.044, OR 2.41, 95% CI 1.01–5.73) compared to healthy controls, suggesting that DQB1*050301 may be associated with susceptibility to HIV infection as well as development of PTB in HIV patients. Underrepresentation of HLA-DPB1*1501 was observed in HIV−PTB+ (p =0.002, P c =0.034) and HIV+PTB+ (p =0.036) patients compared to healthy controls, suggesting that DPB1*1501 may be associated with protection against PTB development both in HIV positive and negative subjects. Analysis on the amino acid variation in the peptide binding pocket at β69 position of HLA-DPB1 molecules revealed that the β69 arginine containing HLA-DPB1 alleles and the genotype lysine/arginine were underrepresented in HIV−PTB+ (allele: p =0.003, P c =0.009; genotype: p =0.0002, P c =0.001) and HIV+PTB+ (allele: p =0.016, P c =0.048; genotype: p =0.026). This suggests that HLA-DPB1 alleles with arginine may be associated with protection against development of PTB in both HIV infected as well as uninfected individuals. Further, the haplotypes HLA-DRB1*1502-DPB1*0201 and HLA-DQB1*0601-DPB1*0201 (P c <0.001) and HLA-DRB1*1502-DQB1*0601-DPB1*0201 (p =0.006, OR 5.09, 95% CI 1.42–22.66) were significantly overrepresented in HIV+PTB+ patients compared to healthy controls suggesting that genetic susceptibility to PTB development in HIV patients may be modulated by interplay between HLA class II alleles, besides HLA class I alleles. [Copyright &y& Elsevier]

Abstract: Some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Many longevity association studies focused their attention on HLA (the human MHC) polymorphisms, but discordant results have been obtained. Sardinians are a relatively isolate population and represent a suitable population for association studies. Some HLA-DR and DQ alleles form very stable haplotypes with a strong linkage disequilibrium. In a previous study on Sardinian centenarians we have suggested that HLA-DRB1∗15 allele might be marginally associated to longevity. HLA-DR,DQ haplotypes are in strong linkage disequilibrium and well conserved playing a role in the association to diseases. Hence, we have evaluated, by amplification refractory mutation system/polymerase chain reaction (ARMS-PCR) the HLADQA1 and HLA-DQB1 allele frequencies in 123 centenarians and 92 controls from Sardinia to assess whether the association to HLA-DRB1∗15 allele may be due to the other genes involved in the HLA-DR,DQ haplotypes. The frequencies of HLA-DQA1,DQB1 haplotypes were not significantly modified in centenarians. Nevertheless by evaluating the frequency of DRB1∗15 linked haplotypes, we observed a not significant increase in centenarians of HLA-DQA1∗01,DQB1∗05 and HLA-DQA1∗01,DQB1∗06 haplotypes. These data suggest that these haplotypes might have a role in determining life span expectancy and longevity. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to investigate the association of human leukocyte antigen (HLA) class II alleles with narcolepsy–cataplexy susceptibility in Koreans. The distribution of HLA-DRB1 and -DQB1 alleles and presence or absence of DRB3/4/5 alleles were examined in 60 narcoleptic patients with clear-cut cataplexy, and the results were compared with two groups of healthy controls: 200 randomly selected controls and 144 DRB1*1501-DQB1*0602 positive controls. All of the narcoleptic patients were DRB1*1501 and DQB1*0602 positive, and their frequencies were significantly higher in patients than in random controls (100% vs 17.0%, pc = 2.3 × 10−30, OR = 583.96; 100% vs 16.5%, p c = 3.9 × 10−31, OR = 605.00). The HLA association in Koreans was as tight as that reported in Japanese. Several DRB1 (*0101, *0405, *0901) and DQB1 alleles (*0303, *0401, *0501, *0601, *0604) were found to have weak protective effects against narcolepsy. DRB4 showed strong protective effect, and this was also significant when compared with DRB1*1501-DQB1*0602 positive controls (18.3% vs 44.4%, p c = 0.001, OR = 0.28). DRB3 (OR = 1.86) and DQB1*0301 (OR = 2.45) were found to have weak predisposing effect, when compared with DRB1*1501-DQB1*0602 positive controls. The protective effect of DRB4 has to be further studied in other populations. [Copyright &y& Elsevier]

Abstract: The vitamin D receptor (VDR) and the human leukocyte antigen (HLA) class II complex affect innate and/or adaptive immunity against Mycobacterium tuberculosis. HLA-DRB1, HLA-DQB1, and VDR gene (VDR) polymorphisms were previously associated with tuberculosis (TB) and are here investigated as candidates for TB susceptibility in the Venda population of South Africa. Genomic DNA from 95 patients with pulmonary tuberculosis (PTB) and 117 ethnically matched, healthy controls were typed for HLA-DRB1, DRB3, DRB4, DRB5, DQB1, and VDR polymorphisms FokI, BsmI, ApaI, and TaqI using polymerase chain reaction-sequence specific primers (PCR-SSP). Allele and haplotype frequencies were calculated by the estimator maximum (EM) algorithm. DRB1*1302 phenotype was significantly associated with TB occurring at a significantly higher allele frequency in cases than controls and found in haplotype with DQB1*0602/3. DQB1*0301-0304 phenotype was significantly associated with TB and found in haplotype with DRB1*1101-1121, showing significant linkage disequilibrium (LD) in both cases and controls. Only DRB1*1101-1121-DQB1*05 was significantly associated with TB based on the sequential Bonferroni p value. VDR SNP phenotypes were not associated with TB, but the haplotype F-b-A-T significantly protected from TB. In conclusion, common African HLA-DRB1 and -DQB1 variants, previously associated with protection from malaria and hepatitis B/C virus persistence, predispose the Venda to TB, whereas the proposedly active VDR haplotype F-b-A-T showed significant protection. [Copyright &y& Elsevier]

Abstract: We investigated potential correlations between soluble HLA-G (sHLA-G) and soluble HLA class I (sHLA-I) levels, respectively, and parameters of disease activity or genetic factors determined by HLA-DRB1 and HLA-DQB1 in patients with rheumatoid arthritis (RA). SHLA-G plasma concentrations from 106 RA patients (mean age 59.8 years, 80 women) were assessed by a sensitive enzyme-linked immunosorbent assay format. The mean sHLA-G levels were lower and sHLA-I levels higher in the RA patients than in healthy controls. Correlation coefficients of 0.248 to 0.344 (p < 0.01) between sHLA-G and rheumatoid factor, CRP, and EULAR joint swelling score were found. Patients with disease-associated HLA epitopes had higher sHLA-G levels than those without. Significantly lower sHLA-G was observed in groups of patients having HLA-DRB1*03 or HLA-DQB1*02 compared to groups without these genotypes. In contrast, HLA-DQB1*03 or disease-associated epitopes combined with HLA-DQB1*03 were associated with higher sHLA-G levels, whereas the inverse was observed in the combined presence of HLA-DRB1*03 and HLA-DQB1*02. SHLA-G as a percentage of sHLA-I was lower in patients positive for HLA-DQB1*02 and higher in patients positive for HLA-DQB1*03 and in its combined presence with disease-associated epitopes or with HLA-DRB1*07. As especially sHLA-G strongly inhibits T and natural killer (NK) cell functions, low sHLA-G suggests that T and NK cell activities are not efficiently restricted by sHLA-G molecules in rheumatoid arthritis. The sHLA-G levels, however, increase in correlation with parameters of disease activity and appear to be affected by the presence of disease-predisposing epitopes and other HLA-DRB1, DQB1 genotypes. [Copyright &y& Elsevier]

Abstract: Bee venom hypersensitivity is a clinical entity of outstanding importance because bee stings are a leading cause of mortality worldwide. Individuals with immediate-type bee venom hypersensitivity, beekeepers, and healthy controls were examined for HLA-DRB1, DQB1, and DQA1 alleles by sequence-specific oligonucleotide probe typing. Defined hypersensitivity to bee venom antigen phospholipase A2 (vbPLA2) is significantly associated with the presence of susceptible HLA class II alleles: DRB1*0101 (RR = 2.7, p &#60; 3 × 10−3), DRB1*0103 (RR = 21.2, p &#60; 7.5 × 10−11), DQA1*0101 (RR = 1.2, p &#60; 38.52 × 10−10), and DQB1*0501 (RR = 4, p &#60; 2.18 × 10−10). Some HLA class I alleles were also associated with risk to bee venom allergy: A*01 (RR = 2.4, p &#60; 7.5 × 10−4), B*57 (RR = 35.1, p &#60; 3.5 × 10−7), and B*5901 (p &#60; 3.5 × 10−5), but they are probably of secondary significance. Three- (DRB1*0103-DQA1*0101-DQB1*0501) (RR = 21.24, p &#60; 7.5 × 10−11) and five-loci (A*01-B*59-DRB1*0103-DQA1*0101-DQB1*0501) (p &#60; 2.3 × 10−6) extended haplotypes are also significantly carried by vbPLA2 allergic patients. When HLA allele frequencies from patients are compared with those from beekeepers, only HLA-DRB1*0103 (RR = 11.7, p &#60; 8.5 × 10−5) and HLA-DQA1*0101 (p &#60; 0.02) were significantly increased in the former. These observations emphasize the importance of the DRB1*0103-DQA1*0101-DQB1*0501 haplotype as a strong candidate for susceptibility to vbPLA2 hypersensitivity, at least in our region. [Copyright &y& Elsevier]

As part of a longitudinal study aimed at defining the natural history of prediabetic autoimmunity and predicting the risk of future cases of type 1 diabetes, 3607 newborns from three regions of continental Italy (Lombardia, Liguria, and Lazio) were subjected to genetic testing to determine human leukocyte antigen-DRB1 (HLA-DRB1) and -DQB1 allele and phenotype frequencies. Polymerase chain reaction and immobilized sequence-specific oligonucleotide probe assays were used to identify ten DRB1 allele lineages and three DQB1 alleles. No major inter-regional differences emerged in the allelic distribution indicating homogeneous distribution of the HLA DRB1-DQB1 alleles among the three regions analyzed. Comparison of our data with those published for other Caucasian populations reveals that these three regions are characterized by a very low frequency of DRB1*04 (8%) and a high frequency of DRB1*11 (25%). The phenotype frequencies of HLA-DQB1*0302 and DQB1*0602 observed are also lower than those reported for other populations. Furthermore, the DRB1*04-DQB1*0302 haplotype was relatively infrequent in our population (5.3% of the newborns tested). These findings furnish a genetic “portrait” of the populations of the analyzed regions that will be useful not only for investigation of the genetic risk of type 1 diabetes mellitus in Italy but also for studies of other autoimmune diseases related to HLA genotypes. [Copyright &y& Elsevier]

Different human leukocyte antigen (HLA) class II alleles have been associated with the development of atopic asthma. To determine whether HLA class II alleles are associated with atopic asthma in a population from southeast Spain (Murcia region), 213 atopic asthmatic patients and 150 controls were selected for HLA typing. Significant association of the DRB1*01 and DQB1*0501 alleles was found in Artemisia vulgaris allergic patients (pc = 0.00052 and pc = 0.00023, respectively). No significant correlation was found in other atopic patients allergic to pollens (Phleum pratense, Olea europaea, and Salsola kali), house dust mites (Dermatophagoides pteronyssinus, D. farinae), molds (Alternaria alternata, Cladosporium herbarum), or animal danders (dog, cat). The results reveal that the DRB1*01-DQB1*0501 genotype is strongly associated with a positive response to Artemisia vulgaris in the population studied. [Copyright &y& Elsevier]

Abstract: Nine novel HLA class I and class II alleles were identified by sequence-based typing (SBT) in Caucasian participants from the Genetics of Kidneys in Diabetes (GoKinD) study. All novel alleles were single nucleotide substitutions. Seven alleles resulted in an amino acid change and two alleles were silent substitutions. The new alleles are as follows: five HLA-A alleles (*0132, *020121, *0344, *030107, *2507), one HLA-C allele (*0619), two HLA-DQB1 alleles (*0204, *0318), and one HLA-DPB1 allele (*1802). Eight of these new alleles were identified in participants with type 1 diabetes, three of whom also had diabetic nephropathy, and one new allele was identified in an unaffected parent of a participant with type 1 diabetes. All new alleles were isolated and characterized by use of single allele amplification (SAA) SBT; the new alleles were confirmed by sequence-specific primer (SSP) amplification. [Copyright &y& Elsevier]

The article presents a study which describes the identification of the novel HLA-DQB1*02:02:01:02 allele in one Spanish Caucasian individual. Cited methods including HLA-DQB1 sequencing, DQB1*02:01 and DQB1*03:02 assessment with the real time polymerase chain reaction, and HLA-DQB1 high resolution typing. Results indicate the similarity of the new allele DQB1*02:02:01:02 to the DQB1*02:02:01:01 regarding to the exon sequences.

Background: Asthma is a heterogeneous disease that is caused by the interaction of genetic susceptibility with environmental influences. Genome-wide association studies (GWASs) represent a powerful approach to investigate the association of DNA variants with disease susceptibility. To date, few GWASs for asthma have been reported. Objectives: A GWAS was performed on a population of patients with severe or difficult-to-treat asthma to identify genes that are involved in the pathogenesis of asthma. Methods: A total of 292,443 single nucleotide polymorphisms (SNPs) were tested for association with asthma in 473 The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) cases and 1892 Illumina general population controls. Asthma-related quantitative traits (total serum IgE, FEV1, forced vital capacity, and FEV1/forced vital capacity) were also tested in identified candidate regions in 473 TENOR cases and 363 phenotyped controls without a history of asthma to analyze GWAS results further. Imputation was performed in identified candidate regions for analysis with denser SNP coverage. Results: Multiple SNPs in the RAD50-IL13 region on chromosome 5q31.1 were associated with asthma: rs2244012 in intron 2 of RAD50 (P = 3.04E-07). The HLA-DR/DQ region on chromosome 6p21.3 was also associated with asthma: rs1063355 in the 3′ untranslated region of HLA-DQB1 (P = 9.55E-06). Imputation identified several significant SNPs in the TH2 locus control region 3′ of RAD50. Imputation also identified a more significant SNP, rs3998159 (P = 1.45E-06), between HLA-DQB1 and HLA-DQA2. Conclusion: This GWAS confirmed the important role of TH2 cytokine and antigen presentation genes in asthma at a genome-wide level and the importance of additional investigation of these 2 regions to delineate their structural complexity and biologic function in the development of asthma. [Copyright &y& Elsevier]