HLA Antigen Frequencies Research Articles

Development of a calculated panel reactive antibody calculator for the United Arab Emirates: a proof of concept study

Calculated panel reactive antibody (CPRA) is used to help increase sensitized patient’s access to transplantation. United Arab Emirates (UAE) has a diverse resident population hence we developed a UAE–CPRA calculator based on HLA antigen frequencies of the different ethnic groups that represent the UAE population. HLA antigen frequencies at serological split antigen level for HLA-A, -B, -C, -DRB1 and -DQB1 of 1002 healthy unrelated donors were performed. We subsequently compared the performance of the UAE CPRA calculator with the Organ Procurement and Transplantation Network (OPTN) and the Canadian CPRA calculators in 110 Kidney Transplant waitlist patients from January 2016 to December 2018. Lin’s concordance correlation coefficient showed a moderate agreement between the UAE and OPTN calculator (Rc = 0.949, 95% CI 0.929–0.963) and the UAE and Canadian calculators (Rc = 0.952, 95% CI 0.932–0.965). While there continued to be a moderate agreement (Rc = 0.937, UAE versus OPTN calculator) in the lower sensitized group, a poor agreement (Rc = 0.555, UAE versus OPTN calculator) was observed in the higher sensitized group. In this study, we provide a template for countries to develop their own population-specific CPRA calculator. Implementation of the CPRA algorithm based on HLA frequencies of the multi-ethnic UAE population will be more fitting to increase access to transplantation and improve transplant outcomes. Our study demonstrates that the CPRA calculators developed using the data from the western population had poor correlation in our higher sensitized patients disadvantaging them in potential organ allocations systems. We plan to further refine this calculator by using high resolution HLA typing to address the problem of a genetically diverse population.

New genetic risk factors for myocardial infarction at young patients in Southern Turkey

Purpose: Genetic predisposition plays an important role in the development of atherosclerosis in young patients. The aim of this study was to determine the relationship between myocardial infarction and HLA antigens in young patients who had myocardial infarction in southern region of Turkey. Materials and Methods: We enrolled 50 patients ( 36 male, 14 female, mean age 45.0  7.1 ) who had myocardial infarction before 45 years old in men and 55 years old in women and 50 healthy subjects (31 male, 19 female, mean age 51.5  5.5 ) as a control group into the study. Venous blood samples were collected for HLA tissue typing and determining trombogenic factors. Histocompatibility antigens (HLA-A,B,C,-DQ,-DR) were studied with Polymerase Chain Reaction (PCR)-Sequance Spesific Oligonucleotide typing (SSO) method. Results: Frequency of HLA antigens in patients and controls were 38% and 10% for HLA-A24, 40% and 10% for HLA-DQB2, 26% and 6% for HLA-DRB1-7 and 52% and 26% for HLA-DRB4-1. Chi square test revealed a significant relation with the disease and the presence of these antigens. In the logistic regression analysis, smoking, Lp(a), homocysteine and HLA-DQB1 subtype were independently associated with development of MI in young patients.Conclusion: The presence of HLA-A24, HLA-DQB2, HLA-DRB1-7 and HLA-DRB4-1 may be used as genetic markers for the tendency to coronary artery disease in southern region of Turkey.

P159 Evaluation of differing methods for calculating cpra for kidney allocation

Aim Currently, there are two different approaches to calculating cPRA. The first, used in USA since 2009, is the expectation maximization (EM) algorithm. The second, utilized in Europe/Canada, is to simply observe the percentage of donors with a particular antigen (“count method”). Recently, the UNOS/OPTN Histocompatibility Committee has been re-evaluating the optimal method for determining cPRA. This has been driven by the need to consider incorporating DP (and other) locus antibodies. The benefit of the EM method, based on haplotype frequencies, is to estimate population frequencies that would include unobserved, rare phenotypes. However, because DP is not in linkage disequilibrium, it may no longer be feasible to use. Here, we evaluate the use of the count method in comparison with the EM approach for determining HLA antigen frequencies in the U.S. donor population. Methods Using the UNOS/OPTN data, we evaluated HLA typings from 39,568 deceased donors from 1/2015–1/2018. We then compared the observed antigen frequencies (count method) with those derived from the UNet cPRA calculator (EM method). Results See table. Download : Download high-res image (81KB) Download : Download full-size image Conclusions There was high concordance between the two methods of calculating cPRA in antigen frequencies within the A, B, and DR loci. Instances where there were large discrepancies were primarily due to parent antigens that were subsequently split; the UNet cPRA was based upon a pool of donors from 2007–9. This suggests, at the very least, that updates to the cPRA calculator are needed. Since DPB is not in linkage disequilibrium with the other loci, thereby negating our ability to use the EM algorithm, we suggest a new updated cPRA calculator be based upon the count method of calculating antigen frequencies.

Wait time deconstructed

Transplant (TX) physicians often ask us: What effects do ABO and HLA antibody sensitization have on my patient’s ability to get an organ offer? This study attempts to answer that question by analyzing waitlist (WL) and TX patient data, ABO and HLA antigen frequency data over a 6 year period for the Tulane kidney transplant program. Data was stratified by presensitization, sex, ABO and TX status. We analyzed this data along with HLA antigen frequency and pertinent organ offer statistics to determine the projected wait time for a highly sensitized (99%) regraft patient with ABO = O. On average, presensitized Tulane WL patients wait 50% longer for an organ than unsensitized patients. The following table gives median wait time stratified by sex, ABO, and TX status. Using the above, ABO and HLA antigen frequencies and frequency and types of organ offers, we projected wait time until a compatible organ offer for a 99% CPRA, regraft male patient awaiting a standard criteria donor with ABO–O in excess of 14 years for an in-state offer. The wait for a regional or national offer is projected to be 63 months, but may be less in the future due to the new allocation system. Wait time is highly dependent on ABO and sensitization, but we also see a disparity in wait times for WL patients vs. TX patients pointing to the effect of HLA antigen frequency. All sensitization is not equal. Many still on the WL likely have less frequent HLA types and higher levels of HLA antibodies to common HLA antigens than those transplanted given all else equal. These data trends provide the TX physician a better understanding of factors affecting wait time. Download : Download full-size image The following table includes transplant (TX) vs. wait list (WL) patient data given in months wait time stratified by sex and CPRA level. Download : Download full-size image

Does the OPTN cPRA Calculator Accurately Predict HLA Antigen Frequencies in Pediatric Donors?

The calculated panel reactive antibody (cPRA) is an estimate of the likelihood of receiving an HLA-incompatible organ based on an historical sample of solid organ donors of all ages, but has not been validated specifically for pediatric donors. We hypothesized that differences in the ethnic makeup of pediatric and infant vs. adult thoracic organ donors would correspond to differences in HLA antigen frequencies not accurately predicted by the current cPRA calculator. All US thoracic donors for the calendar years 2012-2013 were analyzed for the frequencies of A/B/C and DQ antigen frequencies in pediatric (< 18 years) and infant (< 1year) donors as compared to the overall donor pool and to that predicted by the cPRA calculator. A comparison of the ethnic frequencies for each donor group was also conducted. 10,290 thoracic donors were analyzed, including 1119 < 18 years old and 386 < 1 year old. Caucasians made up 73% of the total cohort, 66% of the pediatric cohort, but only 53% of the infant cohort. (P=0.001) African-Americans and Latinos represented larger percentages of the pediatric and infant donor pools when compared to the total donor pool (p=0.001). Although the cPRA calculator accurately predicted the actual antigen frequency in the total cohort within 4 percentage points, it inaccurately predicted the antigen frequency by as much as 9% for 7/70 (10%) and 9/70 (13%) antigens in the pediatric and infant cohorts, respectively (P = 0.02 and 0.05). Differences were most common for antigens commonly found in African-Americans and Latinos (e.g. A36, B53). The national cPRA calculator underestimates the frequency of certain HLA antigens in the pediatric and infant donor pools and may inaccurately estimate the likelihood of receiving an HLA-incompatible organ in these populations. Differences in antigen frequency are likely the result of minority overrepresentation in the pediatric and infant donor pools.

(443) - Pregnancy Outcomes Following Cardiac Transplantation

s S169 Conclusion: The national cPRA calculator is inaccurate at the center-specific level due to wide ethnic variation in donor HLA antigen frequency. Given that the national cPRA calculator may inaccurately estimate the likelihood of an HLA-incompatible donor at any one specific center, moving to a centerspecific or regional cPRA profile may be warranted.

HLA Antigen Distribution in Renal Transplant Patients &amp; Donors Visiting Tertiary Care Hospital of Karnataka State in South India

Renal transplantation is the most successful treatment option for chronic renal failure patients. But success of this depends on HLA antigen matching between the renal recipient & donor. This study is the first report from Karnataka state of South India to find out distribution of HLA-A and B antigens in live renal transplant recipients and donors visiting a tertiary care hospital.In a retrospective study, HLA-A and B allele frequencies were studied in 345 renal transplant recipients & donors visiting our hospital, between 2005-2013. HLA tissue typing was done by polymerase chain reaction using sequence specific primers .Then Allele frequencies were obtained & analysed. A total of 32 HLA-A and 40 HLA-B alleles were identified in the live renal transplant recipients & donors. High frequency A alleles found in our patients & donors were- A*24(16%),A*33(13.6%),A*02(13.5%),A*11(11.4%),A* 01(9.6%). The most frequent alleles in the HLA-B locus were B*40(15%), B*07(13.4%), B*35(12.7%), B*51(8.8%), B*44(7.6%). Also we have found that females dominated among donors. The results showed significant heterogeneity in both HLA-A and B antigens. By knowing the frequency of HLA antigens in population,it is easy to find HLA matched organ transplant recipient & donors from different ethnic background, without a blood relationship.

HLA Class II Alleles Are Associated With Histological Inflammatory Features of Steatohepatitis (NASH): Presidential Poster

Introduction: The genotype-phenotype interaction in chronic liver diseases is a subject of growing interest. Previous studies have linked liver fibrosis susceptibility to specific HLA alleles. In this study we aimed to examine potential associations between HLA class II alleles and histological characteristics and severity in patients with NAFLD/ NASH. Methods: DNA from biopsy-proven NAFLD patients was genotyped using polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) for HLA class II antigens (HLA-DR1, -DR3, -DP &-DQ). Liver biopsies were assessed for hepatic steatosis, inflammation, and fibrosis. Multivariate analysis was performed to draw correlations between HLA antigen frequencies and the different variables; p≤0.05 were considered to be significant. Results: The study cohort include 85 patients with biopsy-proven NAFLD [age=44.25±10.78 years; female=68 (80.0%); white=59 (69.41%); NASH=35 (41.18%); diabetes mellitus=44 (22.4%); hyperlipidemia= 48 (56.47%) 75(38.9%), hypertension=46 (54.12%)]; diabetes=30 (35.29%); portal Inflammation=46 (54.12%), lobular Inflammation: [Kupffer cell hypertrophy=3 (3.8%%), inflammatory cells=18 (21.18%), polymorhnuclear cells=9 (10.59%)], [pericellular fibrosis=33 (38.82%), portal fibrosis=53 (62.35%); bridging fibrosis and cirrhosis=13 (15.29%)] and controls (N=55) without liver disease. DPB1*03 was found to be associated with patients with advanced steatosis [N=7 (31.82%) vs. non-steatosis N=6 (9.52%), p=0.01]. Interestingly DQA*05 was found to be associated with apoptosis and necrosis [N=25 (35.71%) vs. 1 (6.67%, p=0.02]. DRB3*01 was only found in patients with apoptotic or necrotic markers [N=16 (22.86%) vs. 0 (0.00%), p=0.03]. DQA1*03 was associated with higher risk of inflammation [n= 7 (53.85%) vs. 17 (25.76%), p=0.04] than those without inflammation. Inversely, DPA1*01 [n= 3 (33.33%) vs. 64 (84.21%), p<0.001], DPB1*04 [n= 0 (0.00%) vs. 47 (61.84%), p<0.001], DQB1*03 [n=2 (22.22%) vs. 49 (64.47%), p=0.01], and DRB4*01 [n= 2 (22.22%) vs. 47 (61.84%), p=0.04] were associated with lower risk of any type of inflammation. In multivariate analysis, DQA1*03 was independently associated with inflammation [odds ratio (OR): 6.12 (95% CI 1.39-27.73; p=0.01), while DPA1*01 was independently associated with lower risk of any type of inflammation (OR 0.08; 95% CI 0.01-0.61; p =0.01]. Conclusion: HLA-class II genes play important role in determining the disease mechanisms. DQA1*03 alleles play important role in predisposing to sever histological features of NASH among patients with NALFD. These HLA class II alleles that are risk haplotypes may help identify NAFLD patients with increased risk for developing inflammation and sever liver disease.

Identification of Independent Susceptible and Protective HLA Alleles in Japanese Autoimmune Thyroid Disease and Their Epistasis

Autoimmune thyroid disease (AITD) includes Graves disease (GD) and Hashimoto thyroiditis (HT), which partially share immunological features. Determining the genetic basis that distinguishes GD and HT is a key to understanding the differences between these 2 related diseases. The aims of this study were to identify HLA antigens that can explain the immunopathological difference between GD and HT and to elucidate epistatic interactions between protective and susceptible HLA alleles, which can delineate the distinct function of HLA in AITD etiology. We genotyped 991 patients with AITD (547 patients with GD and 444 patients with HT) and 481 control subjects at the HLA-A, HLA-C, HLA-B, DRB1, DQB1, and DPB1 loci. A direct comparison of HLA antigen frequencies between GD and HT was performed. We further analyzed an epistatic interaction between the susceptible and protective HLA alleles in the development of GD and HT. We identified 4 and 2 susceptible HLA molecules primarily associated with GD and HT, respectively, HLA-B*35:01, HLA-B*46:01, HLA-DRB1*14:03, and HLA-DPB1*05:01 for GD and HLA-A*02:07 and HLA-DRB4 for HT. In a direct comparison between GD and HT, we identified GD-specific susceptible class II molecules, HLA-DP5 (HLA-DPB1*05:01; Pc = 1.0 × 10(-9)) and HLA-DR14 (HLA-DRB*14:03; Pc = .0018). In contrast, HLA components on 3 common haplotypes in Japanese showed significant protective effects against the development of GD and HT (HLA-A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01-DPB1*09:01 and HLA-A*24:02-C*07:02-B*07:02-DRB1*01:01-DQB1*05:01-DPB1*04:02 haplotypes for GD and HLA-A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04-DPB1*04:01 haplotype for GD and HT). Interestingly, the representative protective HLA, HLA-DR13 (HLA-DRB1*13:02), was epistatic to susceptible HLA-DP5 in controlling the development of GD. We show that HLA exerts a dual function, susceptibility and resistance, in controlling the development of GD and HT. We also show that the protective HLA allele is partially epistatic to the susceptible HLA allele in GD.

Comparison of HLA Alleles in Follicular Lymphoma and Chronic Lymphocytic Leukemia Patients Referred for Allogeneic Stem Cell Transplantation

AbstractAbstract 4218 Introduction:Data recently published showed that besides the several well-known parameters, long term outcome after allogeneic stem cell transplantation (SCT) in chronic lymphocytic leukemia (CLL) may be influenced by the presence or absence of certain HLA class I alleles (HLA-A1+/A2-/B44-) (Khouri et. Al. Cancer 2011). We have also recently published an 11-year progression free survival (PFS) rate of 72% in relapsed follicular lymphoma (FL) after SCT (Khouri et al. Blood 2012). A higher relapse rate has been observed in CLL patients when compared to FL (50% vs. 4%). Since HLA subtypes played an important role in CLL, our goal in this study was to assess and compare over expressed HLA alleles in FL and CLL patients who received a SCT at our center. Methods:Two cohorts of patients who received SCT were retrospectively studied. Group I consisted of 59 Caucasian patients (23 [39%] F: 36 [61%] M) with FL and Group II consisted of 119 Caucasian patients (27 [23%] F: 112 [77%] M) with CLL. The HLA alleles at HLA-A, -B,-C and -DRB1 loci of both groups were analyzed and the HLA typing was performed by polymerase chain reaction (PCR) amplification and oligonucleotide hybridization using commercial kits from Invitrogen (Carlsbad, Ca) or One Lambda (Canoga Park, Ca) that resulted in intermediate resolution. Patients were also typed for these loci using high-resolution methods with PCR amplification and nucleotide sequencing (Abbott, Abbott Park, Ill).The antigen frequencies of all of the alleles of HLA-A, -B,-C AND DRB1 were calculated. Antigen frequency was defined as the percentage of the population possessing the antigen. Antigen frequency comparisons were only done for North American whites due to sample size and control group constraints. The control group was based on a sample analysis of 643 normal North American Whites. The Pearson x2goodness-of-fit test was used to validate the Hardy-Weinberg genetic equilibrium for phenotypic data. The association of various alleles with the control group was determined by using a chi-square test with Yates correction in a 2 × 2 table with 1 degree of freedom (SAS software, version 6.12, SAS Institute Inc, Cary NC). P values < 0.05 at the 95% confidence interval (95% CI) were considered significant. Results:A male predominance was noted in both patient groups. A total of 17 HLA-A, 29 HLA-B, 13 HLA-C and 13 HLA-DRB1 distinct alleles for FL patients and 16 HLA-A, 24 HLA-B, 13 HLA-C and 11 HLA-DRB1 distinct alleles were identified for the CLL patients. Since the predominant ethnic type in both groups were North American Whites, statistically valid comparisons of HLA antigen frequencies were only possible in this population. The observed heterozygosity for FL/CLL patients was 0.93220./0.831932 for HLA-A, 0.915254/0.949579 for HLA-B, 0.779661/0.882352 for HLA-C and 0.847457/0.941176 for HLA-DRB1. There were no untyped patients and all of the patients underwent hematopoietic stem cell transplantation.Our analysis reveals an over expression of HLA-A*03, HLA-C*04, HLA-DRB1*01, HLA-DRB1*07 and HLA-DRB1*15 with frequencies of 25.4%, 24.1%, 22.9%, 28.8% and 8.5 % in FL patients which was significantly higher than the frequencies of 15.1% for HLA-A*03 (p value 0.005), 1.1% for HLA-C*04 (p value < .00001), 10.3% for HLA-DRB1*01 (p value <.0001), 14.4% for HLA-DRB1*07 (p value < .0001) and 15.7% for HLA-DRB1*15 (p value < .0495) in the normal population showing for the first time an over representation of these alleles in patients with FL.In the CLL group our analysis revealed a 24.8% (p value 0.0014) frequency for HLA-A*01 which was significantly higher than the frequency of 16% (p value 0.0014) in the normal population showing an overrepresentation of this allele. The underrepresented allele was HLA-B*38 with a frequency of 3.4% compared to 12.4% (p value 0.0335) in the normal population.When the two groups FL and CLL patients were analyzed, the significant alleles were HLA-A*01, HLA-A*03, HLA-C*04, HLA-DRB1*01 and HLA-DRB1*07. Conclusion:Our results demonstrate a significant difference in HLA expression in Follicular Lymphoma and Chronic Lymphocytic Leukemia patients with the over representation of HLA-A*03, HLA-C*04, HLA-DRB1*01, HLA-DRB1*07 and HLA-DRB1*15 alleles in FL and HLA-A*01 and HLA-B*38 alleles in CLL. We do not know whether these variances account for a different graft-versus-malignancy susceptibility to donor cells between the two groups and this remains to be studied. Disclosures:No relevant conflicts of interest to declare.

HLA alleles in Brazilian patients with fissured tongue

Fissured tongue (FT) is a clinical condition manifested by numerous little furrows on the tongue's surface. Previously, the authors observed an association with HLA-C×06 in psoriasis (PS) and benign migratory glossitis (BMG); however, HLA-C was not surveyed in FT. This study investigated the association between HLA alleles and FT. Thirty-three FT bearers were studied, after evaluation of criteria for inclusion. These patients did not present PS, BMG or any other conditions associated with FT. The control group (CG) was composed of 561 individuals with HLA-A, 560 individuals with HLA-B, 168 individuals with HLA-C, 564 individuals with HLA-DRB1 and 390 individuals with HLA-DQB1. Samples from these individuals were processed to extract DNA. The HLA classes I and II were determined using the reverse line blot technique. The frequencies of HLA antigens found in patients were compared with the CG using Fisher's exact test. The comparison of the frequencies of HLA antigens found in the patient groups and in CG revealed no association with any of the alleles studied, except for HLA-A*01, which exhibited a decreased frequency in patient groups. HLA-C*06 was detected in 7.57% of FT patients and 10.42% of the CG (not significant). The lack of association of FT with HLA-C*06 reinforces the proposal that this disease does not have a common genetic factor in the triad of BMG, FT and PS.

Frequency of HLA Antigens in a Sample of Iraqi Brucellosis Patients

Fifty one patients with serologically confirmed brucellosis and 70 healthy controls were phenotyped for HLA-A, -B, -DR and -DQ antigens by using standard microlympho-cytotoxicity method, and lymphocytes defined by their CD markers (CD3, CD4, CD8 and CD19). The results revealed a significant (Pc = 0.001) increased frequency of HLA-DR8 (41.18 vs. 10.0%) in the patients . A significant increased percentage of CD8+ lymphocytes was also increased in the patients (25.15 vs. 22.0%; P = 0.006), while CD3+ lymphocytes were significantly decreased (75.1 vs. 79.4%; P = 0.02).

Frequency of HLA Antigens in a Sample of Iraqi Brucellosis Patients

Fifty one patients with serologically confirmed brucellosis and 70 healthy controls were phenotyped for HLA-A, -B, -DR and -DQ antigens by using standard microlympho-cytotoxicity method, and lymphocytes defined by their CD markers (CD3, CD4, CD8 and CD19). The results revealed a significant (Pc = 0.001) increased frequency of HLA-DR8 (41.18 vs. 10.0%) in the patients . A significant increased percentage of CD8+ lymphocytes was also increased in the patients (25.15 vs. 22.0%; P = 0.006), while CD3+ lymphocytes were significantly decreased (75.1 vs. 79.4%; P = 0.02).

Infertility and HLA antigen - male infertility and infertile couples. - Correlation between HLA antigen and infertility.

On the basis of the concept that immunogenetic factors play a role in the incidence of unexplained male infertility, the so-called idiopathic infertility, HLA antigen analyses were performed for (1) azoospermia cases among the infertile males diagnosed by testicular biopsies as having germ cell aplasia and (2) unexplained infertile couples. The results were as follows. (1) The detection frequency of the various HLA antigens of locus A in the azoospermia cases with germ cell aplasia did not differ from that in the controls, but there was a significant increase of BW 35 at locus B (corrected P value< 0.017). (2) In the unexplained infertile couples, frequencies of locus A antigens closely resembled the controls, but there was a significantly higher frequency of BW 35 at locus B. An important future topic for investigation concerning the correlation between infertility and the HLA antigens will be the HLA-D loci on the basis of their correlation with BW 35

HLA-DR4, DR13(6) and the ancestral haplotype A1B8DR3 are associated with ANCA-associated vasculitis and Wegener's granulomatosis

As the HLA system is involved in recognition of self and non-self, an association with the development of ANCA-associated vasculitis (AAV) seems probable. In this study, the relation between HLA antigens and AAV and it's severity were investigated. Consecutive patients diagnosed with AAV at our centre, who were followed for at least 2 years, were included. The frequency of HLA antigens of AAV and WG patients was compared with 5872 healthy blood donors from the same region and with 4000 healthy Dutch controls originating from a Eurotransplant database. From 304 AAV patients, sufficient data were available. We found DR13(6) to be less prevalent and both DR4 and the ancestral haplotype A1B8DR3 more prevalent in patients with AAV compared with controls, particularly in patients with WG. In addition, DR1 was less prevalent in patients with WG in comparison with controls. Further, DR8 was more prevalent in patients with CSS compared with other forms of vasculitis and controls. There were no associations between HLA antigens and disease characteristics or course of AAV or WG. AAV is associated with increased prevalence of DR4 and the ancestral haplotype A1B8DR3 and with decreased prevalence of DR13(6), particularly in patients with WG. In patients with WG, prevalence of DR1 was decreased, whereas in patients with CSS DR8 was increased. No associations between HLA antigens and disease characteristics or course of AAV were found.

HLA Antigens in Omani Psoriasis Vulgaris Patients.

To determine the frequency of different HLA-antigens in patients with plaque psoriasis in the Omani Arab population. Fifty four Omani patients clinically diagnosed with plaque psoriasis attending the dermatology outpatient clinic in Al-Nahdah Hospital (the tertiary dermatology centre in Oman) were selected for HLA studies. HLA-B52 was present in 20.4% of patients 11/54 and in 5% of controls without psoriasis 5/100. For the association p was <0.004 and the relative risk (RR) was 4.86. Psoriasis does not appear to be associated universally with the same HLA antigens. The association of HLA-B52 with plaque psoriasis in Omani patients compares with the HLA-Cw6, -Bw57 and -DR7 preponderance in most other ethnic groups.

Improved Definition of Human Leukocyte Antigen Frequencies Among Minorities and Applicability to Estimates of Transplant Compatibility

HLA population data can be applied to estimates of waiting time and probabilities of donor compatibility. Registry data were used for derivation of HLA antigen and haplotype frequencies in a 1996 report. At that time there were several instances of significant deviation from Hardy Weinberg Equilibrium (HWE). Because molecular typing has been increasingly used since 1996, analysis of recent donor phenotypes should provide more accurate HLA frequencies. HLA frequencies were derived from the phenotypes of 12,061 donors entered into the Organ Procurement and Transplantation Network registry from January 1, 2003 to December 31, 2004. Frequencies for HLA-A;B;DR and HLA-A;B, DR, DQ haplotypes were derived from 11,509 and 10,590 donors, respectively. Frequencies of the allele groups encoding serologic antigens were obtained by gene counting and haplotype frequencies were estimated using the expectation maximization algorithm. Fit to HWE was evaluated by an exact test using Markov Chain Monte Carlo methods. There was clear evidence of improved definition of rarer HLA antigens and haplotypes, particularly among minorities. The reported frequencies of broad antigens decreased overall for HLA-A, B, and DR, with concomitant increases in split antigens. Allele group genotypes among the major ethnic groups were in HWE with the single exception of HLA-A locus alleles among Asians. Improved HLA definition also permitted the first report of DR;DQ and A;B;DR;DQ haplotypes among U.S. donors. The noted improvements in HLA definition and the overall lack of significant deviation from HWE indicate the accuracy of these HLA frequencies. These frequencies can therefore be applied for representative estimates of the U.S. donor population.

Recurrent erythema multiforme: tissue typing in a large series of patients.

Previous reports have shown an increased frequency of certain HLA antigens in association with erythema multiforme, including HLA-B15(B62), HLA-B35, HLA-A33, HLA-DR53 and, more recently, HLA-DQB1*0301. A strong association with HLA-DQ3 has been documented in patients with recurrent erythema multiforme. We have performed HLA typing in 39 patients with recurrent erythema multiforme, of whom 33 were associated with herpes simplex virus infection. The results were compared with 309 controls. In the recurrent erythema multiforme patients there was a statistically significant increase in HLA-B62 and HLA-B35. An increase in HLA-DR53 was also found, although this did not reach statistical significance. There was no increase in HLA-A33. The presence of HLA-DQ3 in the study population approached that in the controls. Finally, the study population demonstrated a trend towards a reduction in the HLA antigens A1, B8 and DR3. The study confirms the previously reported associations with HLA-B62 (B15), HLA-B35 and HLA-DR53. We have been unable to confirm an association of HLA-A33 or HLA-DQ3 with erythema multiforme. The HLA antigens A1, B8, and DR3 are associated with autoimmune disease, reflecting an increased host response to tissue self antigens. Their absence in patients with recurrent erythema multiforme (REM) may be an indicator of a poor host response to an antigen, which in the case of REM is the herpes simplex virus.

Focus on the frequencies of serological HLA antigens in 4,094 Japanese people

Between 1987 and 2005 we performed serological HLA typing in 4,094 Japanese people to evaluate the frequencies of HLA antigens among cancer patients, non-cancer patients and normal subjects. Among these cancer patients compared with non-cancer and normal patients, there were significantly lower frequencies for HLA-24, -A33, -B35, -B44, -DR8, and -DR9, but there was only one significantly lower frequency for HLA-DR8, even after the Bonferroni correction. In cases of gastric cancer, there was a significantly lower frequency for HLA-A33 and -B44 than among non-cancer subjects, even after the Bonferroni correction. In cases of esophageal cancer, significantly lower frequencies for HLA-A33, -B44, -DR6, -DR8, and -DQ4 were found. In cases of hepatoma, the frequency of HLA-DQ3 was significantly lower. In lung cancer, HLA-DR8 and DQ4, and in breast cancer, HLA-Cw3, -DR8, and -DR9 were also significantly lower after the Bonferroni correction. The data demonstrated here shows that there may be an association between different cancers and different antigens. The frequencies of HLA-A33, -B44, -Cw3, -DR6, -DR8, -DR9 and -DQ4 antigens were lower in total; therefore, these antigens may act as defensive factors of carcinogenesis.

HLA antigens as predictors of disease progression in HIV‐infected haemophilia patients (a 22 years’ follow up)

Our objective was to assess the influence of genetic factors such as HLA classes I and II antigens and other clinical and laboratory variables on the progression of HIV disease in a cohort of 118 HIV infected haemophilic subjects of Greek origin who had been typed for HLA antigens and were followed up prospectively for 22 years since seroconversion. At the end of the follow up we compared two groups of patients: 22 patients who had a fast progression to AIDS (median 6 years since seroconversion) vs. 33 patients who remained asymptomatic in stage A2 for up to 22 years (median 15 years). The results showed that the two groups did not differ significantly in age at seroconversion or baseline CD4+ T cell count. However there was a difference in the frequencies of certain HLA antigens in the two groups. The fast progressors had a higher frequency of HLA-A28, B21 and DR3, which was statistically significant (P = 0.02, 0.04, 0.05, respectively) compared to the slow progressors. These findings based on classical HLA typing techniques confirm other published observations and support the effect of genetic background in the progression of HIV infection in haemophilics.