Influence Of Human Leukocyte Antigen Research Articles

Association of HLA Haplotypes with Autoimmune Pathogenesis in Newly Diagnosed Type 1 Romanian Diabetic Children: A Pilot, Single-Center Cross-Sectional Study.

The increasing incidence of autoimmune diseases in type 1 diabetes mellitus (T1DM) patients highlights the influence of human leukocyte antigen (HLA) haplotypes on their development. This study aims to determine genetic predisposition to autoimmune diseases in T1DM patients, including thyroid disease and celiac diseases, and explore its correlation with vitamin D deficiency. A cross-sectional study involving thirty-six T1DM children was conducted. Typing was performed for the HLA A, B, C, DP, DR, and DQ loci. Regression analysis linked DR-DQ haplotypes to T1DM and the associated conditions. The most frequent predisposing alleles and haplotypes were HLA-DR3 (70.27%), DQ2 (70.27%), DR3-DQ2 (70.27%), DQB1*02:01 (70.27%), A02 (54.05%), whereas the most prevalent protecting allele was DPB1*04:01 (52.63%). Positive correlations were observed between positive anti-thyroid peroxidase antibodies and the absence of protective alleles (DPB1*04:02, p = 0.036; DPB1*04:01, p = 0.002). Associations were found between the absence of DPB1*04:01 and anti-thyroglobulin antibodies (p = 0.03). HLA allele DPB1*03:01 was linked with vitamin D deficiency (p = 0.021). Positive anti-transglutaminase antibodies correlated with C03:03 (p = 0.026) and DRB1*04:01-DQA1*03-DQB1*03:01 (p < 0.0001) and the lack of DQA1*01:03-DQB1*06:03-DRB1*13:01 (p < 0.0001). The predisposing T1DM haplotypes were associated with the presence of anti-transglutaminase and anti-thyroid antibodies, indicating a genetic predisposition to autoimmune diseases.

The John Charnley Award: The Impact of Human Leukocyte Antigen Genotype on Bacterial Infection Rates and Successful Eradication in Total Hip Arthroplasty

BackgroundGenetics play an important role in several medical domains; however, the influence of human leukocyte antigen (HLA) genotype on the development of periprosthetic joint infection (PJI) in total hip arthroplasty (THA) remains unknown. The primary aim of this study was to determine if HLA genotype is associated with the development of bacterial PJI in THA. Secondarily, we evaluated the association between HLA genotype and PJI treatment success. MethodsA retrospective, matched, case-control study was performed using prospectively collected data from a single institution. A total of 49 patients who underwent primary THA were included, with a mean follow-up of 8.5 years (range, 4.2 to 12.9). The 23 cases (PJI) and 26 controls (no PJI) were matched for age, sex, follow-up, body mass index, primary diagnosis, and comorbidities (P > .05). High-resolution genetic analysis targeting 11 separate HLA loci was performed in all patients using serum samples. The HLA gene frequencies and carriage rates were determined and compared between cohorts. A subgroup analysis of PJI treatment success (18) and failure (5) was performed. Statistical significance was set at P = .10 for genetic analysis and at 0.05 for all other analyses. ResultsThere were 4 HLA alleles that were significantly associated with the development of PJI. The 3 at-risk alleles included HLA-C∗06:02 (odds ratio 5.25, 95% CI [confidence interval] 0.96 to 28.6, P = .064), HLA-DQA1∗04:01 (P = .096), and HLA-DQB1∗04:02 (P = .096). The single protective allele was HLA-C∗03:04 (odds ratio 0.12, 95% CI 0.01 to 1.10, P = .052). There were no specific HLA alleles that were associated with treatment success or failure. ConclusionsThis study suggests that there are at-risk and protective HLA alleles associated with the development of PJI in THA. To our knowledge, this is the first study to demonstrate an association between patient HLA genotype and the development of PJI. A larger study of the subject matter is necessary and warranted.

Influence of Human Leukocyte Antigen in Susceptibility to Migraine in Patients

Migraine affects more than one billion individuals each year across the world, and is one of the most common neurologic disorders, with a high prevalence and morbidity, especially among young adults and females. Migraine is associated with a wide range of comorbidities, which range from stress and sleep disturbances to suicide. The complex and largely unclear mechanisms of migraine development have resulted in the proposal of various social and biological risk factors, such as hormonal imbalances, genetic and epigenetic influences, as well as cardiovascular, neurological, and autoimmune diseases. Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion, and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache (CH) patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine.

Association between KIR genotypes and HLA-B alleles on viral load in Southern Brazilian individuals infected by HIV-1 subtypes B and C

There is a great variety of HIV-1 subtypes circulating in Brazil, including subtype C, whose prevalence is on the rise, particularly in the southern region. Many host and viral genetic factors may be involved in this trend. We evaluated the influence of human leukocyte antigen (HLA) class I alleles and killer-cell immunoglobulin-like receptor (KIR) genotypes on viral set point and T-CD4+ parameters in 84 treatment-naïve HIV-1-positive individuals. Frequency data in the infected group were compared to data of 548 healthy control subjects. Individuals with the KIR AA genotype had a higher viral load (VL) than individuals with the KIR Bx genotype. The HIV-1 group was subdivided into three subgroups according to HLA-B allele presence: those with protection to disease alleles (HLA-B+), accelerated disease progression alleles (HLA-B−), or neither (HLA-Bo) were grouped. We observed a significant effect of the HLA-B allele presence on VL. The HLA-B+ group had significantly lower VL than the HLA-B− group and trended toward a lower VL than the HLA-Bo group. There were significant differences between groups expressing extreme VL values: KIR-AA+HLA-B− vs. KIR Bx+HLA-B+ and KIR-AA+HLA-Bovs. KIR Bx+HLA-B+. The relationship of KIR/HLA host genetics with slow HIV disease progression in southern Brazil may be useful for vaccine developers, epidemiologists, and clinicians.

Role of Human Leukocyte Antigen Compatibility in Graft Outcomes After Living Donor Liver Transplantation

PurposeThe influence of human leukocyte antigen (HLA) mismatch on liver transplantation has been widely studied, but is still controversial. The aim of this large single-center study was to analyze the role of HLA compatibility between donor and recipient in the graft outcomes of living donor liver transplantation (LDLT). Materials and MethodsA total of 925 recipients who had undergone LDLT between March 2001 and April 2012 were retrospectively analyzed. HLA typing was performed using a standard complement-dependent cytotoxicity technique. The degree and type of HLA-A, HLA-B, and HLA-DR mismatch were assessed. We also investigated the posttransplantation laboratory data, incidence of rejection, recurrence of hepatitis B virus (HBV), and graft survival as outcome parameters. ResultsThe type of HLA-A, HLA-B, and HLA-DR mismatch had no effect on rejection episodes, whereas the beneficial effect of a much lower degree (0–2) of HLA mismatch was notable. Recipients with 2 HLA-B mismatches or recipients with a higher degree of mismatch were associated with elevated bilirubin level, a higher recurrence rate of HBV, and inferior graft survival. A complete mismatch of 2 at the DR locus also decreased graft survival in LDLT recipients. ConclusionsThis study confirmed that the degree of HLA mismatch, as well as the locus-specific type of HLA mismatch, namely B and DR, play a major role in graft outcomes after LDLT. To obtain an improved graft outcome, HLA compatibility should be considered in the setting of LDLT, which provides sufficient time to select a more favorable donor–recipient combination.

Influence of human leukocyte antigen mismatching on bronchiolitis obliterans syndrome in lung transplantation

Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx). The UNOS database was queried for the period 1997 to 2013 to examine HLA mismatching and its association with BOS in LTx. Of 16,959 first-time adult LTx recipients, 16,854 were included in the univariate Cox analysis and Kaplan-Meier survival function evaluation, and 14,578 were included in multivariate Cox models.Multivariate Cox analysis showed that the number of total HLA mismatches was significantly associated with greater hazard of BOS (HR = 1.060; 95% CI 1.013 to 1.108; p = 0.011), as was the presence of 2 HLA-A mismatches, when compared with 0 or 1 mismatch at that locus (HR = 1.128; 95% CI 1.026 to 1.240; p = 0.012). These results were confirmed using competing-risks regression models that adjusted for death before BOS diagnosis. Multivariate Cox models identified no significant association with BOS hazard for HLA-B (HR = 1.014; 95% CI 0.914 to 1.126; p = 0.785) or HLA-DR (HR = 1.085; 95% CI 0.987 to 1.193; p = 0.090) mismatches. Higher body mass index was associated with increased risk for BOS, whereas older age was protective against BOS. Induction with alemtuzumab (HR = 0.343; 95% CI 0.252 to 0.467; p < 0.001) or basiliximab (HR = 0.862; 95% CI 0.758 to 0.980; p = 0.023) and longer ischemic time (HR = 0.909; 95% CI 0.877 to 0.942; p < 0.001) were associated with lower hazard of BOS. Total HLA mismatches are associated with increased risk for BOS, specifically at the A locus. Induction with alemtuzumab or basiliximab reduced the risk, whereas greater ischemic time appears to also be protective.

Human leukocyte antigen mismatching and survival after lung transplantation in adult and pediatric patients with cystic fibrosis

IntroductionThe influence of human leukocyte antigen (HLA) mismatching on survival in adult and pediatric patients with cystic fibrosis (CF) after lung transplantation (LTx) is unknown. MethodsThe United Network for Organ Sharing database was queried from 1987 to 2013 to determine the influence of HLA mismatching on survival in adult and pediatric CF LTx recipients by assessing the association of HLA mismatching with survival in first-time adult (aged ≥ 18 years) and pediatric (aged <18 years) recipients. ResultsOf 3149 adult and 489 pediatric patients with CF, 3145 and 489 were used for univariate Cox analysis, 2687 and 363 for Kaplan-Meier survival analysis, and 2073 and 257 for multivariate Cox analysis, respectively. Univariate analyses in adult and pediatric patients with CF demonstrated conflicting associations between HLA mismatching and survival (adult hazard ratio [HR], 1.0; 95% confidence interval [CI], 0.97-1.1; P = .45 vs pediatric HR, 0.87; 95% CI, 0.77-0.99; P = .032). Multivariate Cox models including both pediatric and adult patients confirmed that HLA mismatching had an initially protective effect at young ages (HR, 0.85; 95% CI, 0.73-0.99; P = .044) and that this protective effect diminished at older ages and was no longer associated with survival at P < .05 beyond age 10 years. ConclusionsHLA mismatching has significantly different implications for survival after LTx in adult compared with pediatric patients with CF.

HLA Alleles Association with Changes in Bone Mineral Density in HIV-1-Infected Adults Changing Treatment to Tenofovir-Emtricitabine or Abacavir-Lamivudine

BackgroundThere are limited data regarding the influence of human leukocyte antigen (HLA) polymorphisms on reduced bone mineral density (BMD). We investigated the relationship between HLA supertypes and BMD in HIV-infected adults changing their existing treatment to tenofovir-emtricitabine (TDF-FTC) or abacavir-lamivudine (ABC-3TC) in the STEAL study.MethodsLumbar spine and right hip BMD were measured by Dual-energy X-ray absorptiometry (DXA). HLA genotypes at the 2-digit level were classified into class I and II supertypes. Student's t-tests were used to test the association between HLA supertypes and changes in hip and spine BMD over 96 weeks for the whole cohort and stratified by randomised groups. The relationship between HLA supertypes and BMD was also assessed in the subgroup of participants that were naïve to both ABC and TDF at study entry.ResultsClass II supertypes were mainly associated with hip BMD change. Overall, compared to participants not carrying HLA-DQ3, participants expressing DQ3 had less bone loss over 96 weeks at both the hip and spine (hip: 0.003 vs. −0.006 g/cm2, 95%CI 0.002 to 0.017, p = 0.016; spine: 0.006 vs. −0.006 g/cm2, 95%CI 0.001 to 0.023, p = 0.041). In participants that were naïve to both ABC and TDF at baseline and randomised to TDF-FTC, DQ3 was significantly associated with less bone loss compared with those not carrying DQ3 (hip: 0.001 vs. −0.032 g/cm2; diff 0.033; 95%CI 0.017 to 0.049; p<0.001; spine: 0.007 vs. −0.023 g/cm2; diff 0.035; 95%CI 0.014 to 0.056; p = 0.001).ConclusionsIn this cohort of HIV-infected adults, there was an association between bone status and HLA supertypes, particularly HLA-DQ3.Trial RegistrationClinicaltrials.gov NCT00192634

HLA variants related to primary sclerosing cholangitis influence rejection after liver transplantation.

To investigate influence of human leukocyte antigen (HLA) and killer immunoglobuline-like receptor (KIR) genotypes on risks of acute rejection (AR) after liver transplantation (LTX). In this retrospective study we included 143 adult donor-recipient pairs with a minimum of 6 mo follow-up after LTX for whom DNA was available from both donor and recipients. Clinical data, all early complications including episodes and severity of AR and graft/patient survival were registered. The diagnosis of AR was based on clinical, biochemical and histological criteria. All suspected episodes of AR were biopsy confirmed. Key classical HLA loci (HLA-A, HLA-B, HLA-C and HLA-DRB1) were genotyped using Sanger sequencing. 16 KIR genes were genotyped using a novel real time PCR approach which allows for determination of the diploid copy number of each KIR gene. Immunohistochemical staining for T (CD3), B (CD20) and natural killer (NK) cells (CD56 and CD57) were performed on liver biopsies from 3 different patient groups [primary sclerosing cholangitis (PSC), primary biliary cirrhosis and non-autoimmune liver disease], 10 in each group, with similar grade of AR. Fourty-four (31%) patients were transplanted on the basis of PSC, 40% of them had AR vs 24% in the non-PSC group (P = 0.04). No significant impact of donor-recipient matching for HLA and KIR genotypes was detected. In the overall recipient population an increased risk of AR was detected for HLA-B*08 (P = 0.002, OR = 2.5; 95%CI: 1.4-4.6), HLA-C*07 (P = 0.001, OR = 2.4; 95%CI: 1.4-4.0) and HLA-DRB1*03 (P = 0.03, OR = 1.9; 95%CI: 1.0-3.3) and a decreased risk for HLA-DRB1*04 (P = 0.001, OR = 0.2; 95%CI: 0.1-0.5). For HLA-B*08, HLA-C*07 and DRB1*04 the associations remained evident in a subgroup analysis of non-PSC recipients (P = 0.04, P = 0.003 and P = 0.02, respectively). In PSC recipients corresponding P values were 0.002, 0.17 and 0.01 for HLA-B*08, HLA-C*07 and DRB1*04, respectively. A dosage effect of AR prevalence according to the PSC associated HLA alleles was also notable in the total recipient population. For HLA-B*08 the frequency of AR was 56% in HLA-B*08 homozygous recipients, 39% in heterozygous recipients and 21% in recipients lacking HLA-B*08 (P = 0.02). The same was observed for the HLA-C*07 allele with AR in 57%, 27% and 18% in recipients being homozygous, heterozygous and lacking HLA-C*07 respectively (P = 0.003). Immunohistochemical analysis showed similar infiltration of T, B and NK cells in biopsies with AR in all three groups. We found significant associations between the PSC-associated HLA-B*08, HLA-C*07, HLA-DRB1*03 and HLA-DRB1*04 alleles and risk of AR in liver transplant recipients.

New insights into HLA class I association to Behçet's syndrome in Iranian Azari patients.

Behçet’s syndrome (BS) is a chronic recurrent inflammatory disorder characterized by oral and genital ulcers and ocular inflammation. BS has a complex genetic etiology. To evaluate the influence of human leukocyte antigen (HLA) class I in BS susceptibility in Iranian Azari population, we studied 290 BS patients and 300 healthy controls. As expected, a high frequency of HLA-B5 was found. Remarkably, HLA-B35 frequency was higher in the patient than control group, and the frequency of HLA-B51, HLA-B52, and HLA-BW4 was significantly elevated. Thus, HLA-B5 and HLA-B35 seem to confer susceptibility to BD in Iranian Azari patients.

Low mannose-binding lectin serum levels are associated with reduced kidney graft survival

Activation of the complement system is initiated by the alternative, the classical, or the lectin pathway. As the complement system is involved in the pathophysiology of graft rejection after kidney transplantation, we investigated the possible role of mannose-binding lectin in kidney transplantation and the influence of human leukocyte antigen (HLA) immunization on this process. In a prospective study of 544 kidney transplant patients over a follow-up period of 5 years, low serum levels of this lectin at the time of transplantation were found to be significantly associated with decreased 5-year death-censored graft survival (hazard ratio 1.68). Subanalysis showed that this association was confined to non-HLA-immunized patients (hazard ratio 1.93). The strongest association was seen in non-HLA-immunized patients receiving a kidney from a deceased donor (hazard ratio 2.93). No significant association with mannose-binding lectin levels and graft survival were found in HLA-immunized patients. Variant MBL2 genotypes causing low mannose-binding lectin serum concentrations showed the same association pattern. Our findings demonstrate a clear protective role of mannose-binding lectin and thus innate immunity in maintaining kidney graft survival, but these are probably overruled by HLA immunization.

Influence of human leukocyte antigen mismatching on rejection development and allograft survival in liver transplantation: Is the relevance of HLA-A locus matching being underestimated?

The influence of HLA matching on liver transplant is still controversial, as studies have failed to demonstrate an adverse effect of HLA mismatching on transplant outcome. We examined the effect of HLA mismatching on transplant outcome in a series of 342 consecutive liver transplants (224 finally analyzed). HLA typing was performed by serological and molecular methods.HLA-A matching was associated with an increased chronic rejection incidence (P=0.04). Indeed, HLA-A match also demonstrated a significant impact on allograft survival (P=0.03), confirming previous observation concerning to rejection, as complete HLA-A mismatching favored a better liver transplant outcome. Analysis of HLA-A+B+DR matching also demonstrated a significant impact on graft survival (P<0.05).Multivariate Cox regression analysis confirmed the effect of HLA-A and DPB1 matching as independent risk factors for graft loss. Another independent factor was a positive pre-transplant crossmatch.In conclusion, liver transplant outcome has not been found to be improved by HLA matching, however a poorer HLA compatibility favored a better graft survival and decreased rejection incidence, with a special relevance for HLA-A matching.

A new risk factor for the development of non-alcoholic fatty liver disease: HLA complex genes

Several studies have emphasized the role of genetic factors in susceptibility to non-alcoholic fatty liver disease. The aim of this study was to examine the possible influence of human leukocyte antigen in the development of non-alcoholic fatty liver disease. Between January 2000 and January 2008, data of 655 donor candidates were examined from routinely performed abdominal ultrasonography and for aspartate aminotransferase, alanine aminotransferase, hepatitis B virus, hepatitis C virus, cytomegalovirus, human immunodeficiency virus, hepatic functions, and human leukocyte antigen class I and II antigens; data of 116 healthy candidates were also included in this study. To reduce the influence of possible confounding factors, we excluded diseases known to be associated with non-alcoholic fatty liver disease like obesity, diabetes mellitus, coronary artery disease, hyperlipidemia, and metabolic syndrome. Non-alcoholic fatty liver disease was diagnosed in 66 individuals (33 male, median age: 53.8 [range, 32-77 years]) by means of ultrasonography data, and 50 individuals, whose ultrasonography data did not show hepatosteatosis, comprised the control group (20 male, median age: 44.6 [range, 26-71 years]). Human leukocyte antigen-B65 (28.8% vs 0%, p<0.001) and DQ5 (40.7% vs 16.1%, p<0.05) were found to be expressed significantly more in non-alcoholic fatty liver disease compared with controls. Serum alanine aminotransferase (27.1 IU/L vs 20 IU/L, p<0.05) was significantly higher in the study group. Our preliminary study suggests that human leukocyte antigen plays a role in the pathogenesis of non-alcoholic fatty liver disease; however, more studies are needed to clarify these data.

Strong influence of human leukocyte antigen (HLA)-DP gene variants on development of persistent chronic hepatitis B virus carriers in the Han Chinese population

Chronic hepatitis B virus (HBV) infection is a major health issue, especially in Asia. A recent genome-wide association study (GWAS) implicated genetic variants in the human leukocyte antigen (HLA)-DP locus associated with chronic hepatitis B in Japanese and Thai populations. To confirm whether the polymorphisms at the HLA-DP genes are associated with persistent chronic HBV infection in Han Chinese, we conducted an independent case-control study using 521 persistent chronic HBV carriers and 819 controls that included 571 persons with HBV natural clearance and 248 never HBV-infected (healthy) individuals. Eleven single nucleotide polymorphisms (SNPs) in a region including HLA-DPA and HLA-DPB and an adjacent SNP in strong linkage disequilibrium (LD) with a neighboring HLA-DR13 locus were genotyped using the TaqMan SNP genotyping assay. Eleven variants at HLA-DP showed a strong association with persistent chronic HBV carrier status (P = 1.82 × 10(-12) to 0.01). We also stratified the analysis by HBV clearance status to test the association between these polymorphisms and HBV natural clearance; similar results were obtained (P = 2.70 × 10(-11) to 0.003). Included SNPs define highly structured haplotypes that were also strongly associated with HBV chronic infection (block 1: odds ratio [OR] = 0.54, P = 8.73 × 10(-7) ; block 2: OR = 1.98, P = 1.37 × 10(-10) ). These results further confirm that genetic variants in the HLA-DP locus are strongly associated with persistent HBV infection in the Han Chinese population.

Human leukocyte antigen type and progression from onset of symptoms to development of asthma.

This study investigated the influence of human leukocyte antigen (HLA) genes on the progression of asthma, from the initial onset of symptoms to when criteria for asthma are met. Study subjects were a subsample (n = 340) of 838 healthy children, aged 5-12 years, who participated in a previous study, and who had HLA data and asthma status. The duration in time from the initial onset of asthma symptoms documented in each subject's medical records to the index date when the subject first met criteria for asthma was determined. The time duration was compared between carriers and noncarriers of HLA genes of interest of the 340 original subjects with HLA data available, 114 children (33.5%) met criteria for asthma before 18 years of age. The median ages at onset of asthma symptoms and at the index date of asthma were 4.4 years and 7.2 years, respectively. The median time intervals between onset of symptoms and index date for HLA DRB1*11 carriers and noncarriers were 552 versus 61 days, respectively (p = 0.004). The same time intervals for HLA DQB1*0301 carriers and noncarriers were 420 versus 59 days, respectively (p = 0.012). However, HLA DQB1*0302 or DRB1*03 carriers had shorter median intervals, when compared with noncarriers (119 versus 266 days, respectively, p = 0.20; and 86 versus 258 days, respectively, p = 0.38) but they did not reach statistical significance. HLA type appears to influence the progression of asthma from initial symptoms to disease. Thus, genetic factors may affect the natural history of asthma.

HLA‐Bw4Homozygosity Is Associated with an Impaired CD4 T Cell Recovery after Initiation of Antiretroviral Therapy

We assessed the influence of human leukocyte antigen (HLA) alleles HLA-Bw4 and HLA-Bw6 on CD4 T cell recovery after starting successful combination antiretroviral therapy in 265 individuals. The median gains in the CD4 T cell count after 4 years were 258 cells/microL for HLA-Bw4 homozygotes, 321 cells/microL for HLA-Bw4/Bw6 heterozygotes, and 363 cells/microL for HLA-Bw6 homozygotes (P = .01, compared with HLA-Bw4 homozygotes). HLA-Bw4 homozygosity appears to predict an impaired CD4 T cell recovery after initiation of combination antiretroviral therapy.

Effect of Human Leukocyte Antigen Compatibility on Kidney Graft Survival: Comparative Analysis of Two Decades

Based on an analysis of United Network for Organ Sharing data, it was reported that the influence of human leukocyte antigen (HLA) matching in renal transplantation has diminished in recent years, prompting the suggestion that donor kidney allocation algorithms should be revised. We compared the impact of HLA matching on kidney graft survival during the decades 1985-1994 and 1995-2004 using the data of the Collaborative Transplant Study. Results for the last 5 years (2000-2004) were analyzed separately in addition. Multivariate Cox regression analysis was used to account for the influence of confounders. Our results show that, while graft survival rates have improved overall over time, the relative impact of HLA matching on the graft survival rate has remained strong and highly significant. Both the need for posttransplant rejection treatment and the graft survival rates showed statistically highly significant associations with HLA matching regardless of the interval analyzed (P<0.001). We conclude that HLA mismatches significantly influence the outcome of kidney transplants and that kidney exchange programs for the purpose of achieving better HLA matches continue to be meaningful.

Influence of HLA antigens and OSAS in childhood: a preliminary report*

Several studies have emphasized the role of familial factors and familial aggregation in increasing susceptibility to obstructive sleep apnea syndrome (OSAS); the aim of the present study was to investigate the possible influence of human leukocyte antigen (HLA) in the development of sleep disordered breathing and OSAS of children. Between January 2000 and January 2003, all the 370 children [193 males; median age: 5.2 years (range: 1-12 years)] with sleep disordered breathing referred to our Center were screened by a 41-item multiple-choice questionnaire. All habitual snores children underwent a polisomnographic evaluation, and those with an apnea/hypopnea index >3 were diagnosed as having OSAS. All children with OSAS or primary snoring were HLA typed for class I and II. According to nocturnal polygraphic monitoring study, 41 patients were diagnosed as having OSAS and 32 as primary snoring. Patients in the two diagnostic groups were homogeneous for demographic and clinical characteristics. HLA-B65 was found to be significantly more expressed in children with sleep disordered breathing as compared with controls (10.5% versus 3.61; Pypc < 0.04) while no difference was found for the other tested antigens. A logistic regression analysis found cough (P < 0.02) and persistent wheeze (P < 0.008) the sole risk factors for OSAS development. Our preliminary data suggest that HLA does not play a key role in the pathogenesis of OSAS, however more studies are needed to clarify this issue.

Human leukocyte antigen-DQB1 and -DRB1 associations in patients with idiopathic sudden sensorineural hearing loss from a defined population of Northwest Spain

Conclusion. The results of this study support the assertion that Southern European individuals have a genetically mediated predisposition to develop idiopathic sudden sensorineural hearing loss (SNHL). Objective. To assess the influence of human leukocyte antigen (HLA)-DQB1 and -DRB1 alleles on the susceptibility to and the severity of idiopathic sudden SNHL. Material and methods. A prospective study of patients diagnosed with idiopathic sudden SNHL between October 2000 and September 2002 was conducted. Patients were included in the study if they were diagnosed with idiopathic sudden SNHL within 1 week after the onset of deafness symptoms and had been followed for at least 12 months. HLA-DQB1 and -DRB1 typing was performed from DNA using molecular-based methods on patients and ethnically matched healthy controls. Results. Thirty-three patients fulfilled the inclusion criteria. No significant differences in HLA-DQB1 phenotype frequencies were found between patients and controls (n=145). Carriage of HLA-DRB1*0403 was significantly increased in the whole group of patients compared with controls (OR = 11.97; 95% CI 1.99–91.60; p=0.002; pcorr=0.04). In patients without auditory improvement the frequency of the HLA-DRB1*04 phenotype was significantly increased compared with healthy controls (OR = 6.57; 95% CI 1.62–26.70; p=0.003; pcorr=0.04).

HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease.

Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HLA) class II molecules on the predisposition to DIILD. We sought associations between HLA-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P =.002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P =.001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P =.003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P =.0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HLA allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage.