Human Leukocyte Antigen Groups Research Articles

Complimentary electrostatics dominate T-cell receptor binding to a psoriasis-associated peptide antigen presented by human leukocyte antigen C∗06:02

Psoriasis is a chronic skin disease characterized by hyperproliferative epidermal lesions infiltrated by autoreactive T cells. Individuals expressing the human leukocyte antigen (HLA) C∗06:02 allele are at highest risk for developing psoriasis. An autoreactive T cell clone (termed Vα3S1/Vβ13S1) isolated from psoriatic plaques is selective for HLA-C∗06:02, presenting a peptide derived from the melanocyte-specific autoantigen ADAMTSL5 (VRSRRCLRL). Here we determine the crystal structure of this psoriatic TCR-HLA-C∗06:02 ADAMTSL5 complex with a stabilized peptide. Docking of the TCR involves an extensive complementary charge network formed between negatively charged TCR residues interleaving with exposed arginine residues from the self-peptide and the HLA-C∗06:02 α1 helix. We probed these interactions through mutagenesis and activation assays. The charged interface spans the polymorphic region of the C1/C2 HLA group. Notably the peptide-binding groove of HLA-C∗06:02 appears exquisitely suited for presenting highly charged Arg-rich epitopes recognized by this acidic psoriatic TCR. Overall, we provide a structural basis for understanding the engagement of melanocyte antigen-presenting cells by a TCR implicated in psoriasis while simultaneously expanding our knowledge of how TCRs engage HLA-C.

AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury.

AASLD practice guidance on drug, herbal, and dietary supplement-induced liver injury.

Dual Role of PTPN22 but Not NLRP3 Inflammasome Polymorphisms in Type 1 Diabetes and Celiac Disease in Children.

Genetic polymorphisms in genes coding for inflammasome components nucleotide-binding oligomerization domain leucine rich repeat and pyrin domain-containing protein 3 (NLRP3) and caspase recruitment domain-containing protein 8 (CARD8) have been associated with autoinflammatory and autoimmune diseases. On the other hand several studies suggested that NLRP3 inflammasome contributes to maintenance of gastrointestinal immune homeostasis and that activation of NLRP3 is regulated by protein tyrosine phosphatase non-receptor 22 (PTPN22). PTPN22 polymorphism was implicated in the risk for various autoimmune diseases including type 1 diabetes (T1D) but not for celiac disease (CD). The aim of our study was to evaluate the role of inflammasome related polymorphisms in subjects with either T1D or CD as well as in subjects affected by both diseases. We examined PTPN22 rs2476601 (p.Arg620Trp), NLRP3 rs35829419 (p.Gln705Lys), and CARD8 rs2043211 (p.Cys10Ter) in 66 subjects with coexisting T1D and CD, 65 subjects with T1D who did not develop CD, 67 subjects diagnosed only with CD and 127 healthy unrelated Slovenian individuals. All results were adjusted for clinical characteristic and human leukocyte antigen (HLA) risk. PTPN22 rs2476601 allele was significantly more frequent among subjects with T1D (Padj = 0.001) and less frequent in subjects with CD (Padj = 0.039) when compared to controls. In patients with coexisting T1D and CD this variant was significantly less frequent compared to T1D group (Padj = 0.010). Protective effect on CD development in individuals with T1D was observed only within the low risk HLA group. On the other hand, we found no association of NLRP3 rs35829419 and CARD8 rs2043211 with the development of T1D, CD or both diseases together. In conclusion PTPN22 rs2476601polymorphism was significantly associated with the risk of developing T1D in Slovenian population, while no associations of proinflammatory NLRP3 and CARD8 polymorphisms with T1D and CD were observed. Interestingly, the same PTPN22 variant protected from CD. We hypothesize that this effect may be mediated through the NLRP3 inflammasome activation.

Impact of HLA Allele-KIR Pairs on Disease Outcome in HIV-Infected Thai Population.

Class I human leukocyte antigen (HLA) molecules contribute to HIV control through antigen presentation to both cytotoxic T lymphocytes and natural killer cells. Contribution of cytotoxic T lymphocytes to HIV clinical outcome by HLA alleles has been well studied. However, reports about the role of natural killer cells in HIV clinical outcome, particularly, about the effect of HLA-killer immunoglobulin-like receptor (KIR) pairs, remain incomplete. The effects of HLA allele-KIR pairs on HIV clinical outcome were statistically analyzed in a Thai cohort of treatment-naive chronically infected population (n = 209). Five HLA allele-KIR pairs scored significantly in viral load (VL) differences. Among them, opposing effects on VL were identified among subjects expressing KIR2DL2 ligands within the HLA-C1 group: higher VL in individuals expressing HLA-B*46:01+KIR2DL2+ compared with individuals without KIR (HLA-B*46:01+KIR2DL2-) (5.0 vs 4.6 log10 copies/mL, P = 0.02), in HLA-C*01:02+KIR2DL2+ (5.0 vs 4.6 log10 copies/mL; P = 0.02), and lower VL in HLA-C*12:03+KIR2DL2+ (4.3 vs 5.6 log10 copies/mL; P = 0.01). In the longitudinal analysis of a ten-year follow-up, HLA-B*46:01+KIR2DL2+ve subjects also had a higher mortality rate compared with the subjects without that pair, independent of variables including antiretroviral treatment, as well as CD4 T-cell count, sex, and age (adjusted hazard ratio 5.9, P = 0.02). We identified several HLA allele-KIR pairs associated with clinical outcome differences including opposing effects on VL within 1 HLA group with the same KIR. Among them, HLA-B*46:01 emerged in Southeast Asia about 50,000 years ago and is now the most prevalent HLA-B allele in that area. These findings highlight that each endemic area has unique features of anti-HIV innate immunity that impact clinical outcome.

Prevalence and Risk Factors of BK Viremia in Patients With Kidney Transplantation: A Single-Center Experience From Turkey

BackgroundBK virus is the cause of nephropathy, which can progress to graft loss after kidney transplantation. In this study, we aimed to investigate the prevalence and risk factors of BK viremia in patients with kidney transplantation at our center. MethodsThis was a retrospective single-center study. We included recipients transplanted between 2010 and 2015. Patients were stratified according to BK virus DNA follow-up values into three groups (0–999 copies/mL, 1000–9999 copies/mL and ≥10,000 copies/mL). The parametric t test and the non-parametric χ2 test were used to detect differences between groups. Multivariate analysis was used to identify risk factors for BK viremia. ResultsOne hundred eighty-three patients were included in the study, with mean follow-up time of 33.6 ± 14.9 months. BK viremia prevalence was found 15.8% (n = 29), and time to detection of viremia was 7.6 months. Cadaveric transplantation and matching human leukocyte antigen (HLA) A24 and HLA B55 subgroups were found to be independent risk factors for BK viremia [odds ratio (OR), 3.65; 95% confidence interval (CI), 1.42–9.39; P < .001; OR, 4.94; 95% CI, 1.84–13.2; P < .001 and OR, 14.03; 95% CI, 1.07–183.5; P = .04, respectively]. Risk factors for BKV level ≥10,000 copies/mL cadaveric transplantation, male sex, and HLA A24 matching (OR, 4.53; 95% CI, 1.49–13.7; P < .001; OR, 3.47; 95% CI, 1.11–10.86; P = .03 and OR, 3.63; 95% CI, 1.08–12.1; P = .03, respectively). ConclusionsPatients should be followed more carefully for BK viremia who have cadaveric transplantation, are male, and have matching in certain HLA groups, which were independent risk factors in the present study. Our results are important to individualize screening methods and provide early diagnosis in our country.

Abstract 1289: Renal cell carcinoma patients have altered HLA expression patterns which show correlations to clinical parameter

Abstract The aim of this study was to evaluate altered HLA (Human Leukocyte Antigen) expression patterns of renal cell carcinoma (RCC) patients and healthy control persons (blood donors). Peripheral blood samples from RCC patients and from healthy controls were investigated for the incidence of HLA groups. The frequency of HLA groups was analyzed statistically and correlated with relevant clinical data. In addition, HLA subtypes were analyzed for RCC patients and for healthy blood donors. A multidimensional statistical comparison was performed. An update of the follow up for RCC patients was conducted in 2014. After following the CD45 autoMACS depletion protocol, we identified CTCs in 96 out of 233 peripheral blood samples (41%), which originated from 81 out of 154 (53%) RCC patients. We detected two HLA groups, HLA-Cw*07 and HLA-DRB1*04 that were significantly higher in healthy controls than in RCC patients (p &amp;lt; 0.05), respectively. In a Kaplan-Meier survival analysis these results were confirmed (p &amp;lt; 0.05). On the one hand, RCC patients had less alleles HLA-Cw*07 (p &amp;lt; 0.05; χ2-test) and HLA-DRB1*04 (p &amp;lt; 0.05; χ2-test) compared to healthy blood donors. On the other hand, RCC patients showed an increased occurrence of the allele HLA-Cw*12 compared to healthy blood donors. There are HLA groups that occur less often in RCC patients than in healthy controls. But it needs larger study populations and further immunological studies to investigate if special HLA-types can have a protective effect against RCC carcinogenesis. Occurrence of the alleles HLA-Cw*07, and HLA-DRB1*04 was significantly altered in RCC patients compared to healthy blood donors and may change the risk to suffer from a RCC. The integration of our results in systematic functional studies will help to earlier identify persons with an increased risk of RCC development and may have an impact in future patient care. Citation Format: Steffen Goebel, Karen Bluemke-Anbau, Wolfgang Altermann, Udo Bilkenroth, Axel Meye, Susanne Fuessel, Astrid Kehlen, Christine Lautenschlaeger, Andres Melchior, Paolo Fornara, Helge Taubert. Renal cell carcinoma patients have altered HLA expression patterns which show correlations to clinical parameter. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1289. doi:10.1158/1538-7445.AM2015-1289

A human-specific allelic group of the MHC DRB1 gene in primates

BackgroundDiversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the HLA loci are the most polymorphic in the human genome. One characteristic of HLA diversity is long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species. Modern humans have disseminated across the world after their exodus from Africa, while chimpanzees have remained in Africa since the speciation event between humans and chimpanzees. It is thought that modern humans have recently acquired resistance to novel pathogens outside Africa. In the present study, we investigated HLA alleles that could contribute to this local adaptation in humans and also studied the contribution of natural selection to human evolution by using molecular data.ResultsPhylogenetic analysis of HLA-DRB1 genes identified two major groups, HLA Groups A and B. Group A formed a monophyletic clade distinct from DRB1 alleles in other Catarrhini, suggesting that Group A is a human-specific allelic group. Our estimates of divergence time suggested that seven HLA-DRB1 Group A allelic lineages in humans have been maintained since before the speciation event between humans and chimpanzees, while chimpanzees possess only one DRB1 allelic lineage (Patr-DRB1*03), which is a sister group to Group A. Experimental data showed that some Group A alleles bound to peptides derived from human-specific pathogens. Of the Group A alleles, three exist at high frequencies in several local populations outside Africa.ConclusionsHLA Group A alleles are likely to have been retained in human lineages for a long period of time and have not expanded since the divergence of humans and chimpanzees. On the other hand, most orthologs of HLA Group A alleles may have been lost in the chimpanzee due to differences in selective pressures. The presence of alleles with high frequency outside of Africa suggests these HLA molecules result from the local adaptations of humans. Our study helps elucidate the mechanism by which the human adaptive immune system has coevolved with pathogens over a long period of time.

Genetic diversity among volunteer donors of bone marrow in southeastern Brazil, according to the HLA system.

Checking the histocompatibility of the molecules of the human leukocyte antigen (HLA) system is vital for performing bone marrow transplantation with allogeneic material. The objective of this study was to characterize bone marrow donors according to gender, age, ethnicity and HLA groups at a regional hemotherapy center in Brazil. Descriptive study on registered donors at a regional hemotherapy center in a public university hospital in the southeastern region of Brazil. The records of 66,780 donors who were registered between 2005 and June 2011 were consulted, and the variables studied were tabulated. There were equal numbers of male and female donors and 82.8% of them were under 45 years of age. In terms of ethnicity, 77.3% declared themselves to be white, 15.0% mixed race, 5.7% black and 2% others. In terms of immunogenetic characterization, the most frequent HLA-A allelic group was HLA-A*02, with 39.20% of the donors; in the HLA-B allelic group, the most common was HLA-B*35, with 14.18%; while in the HLA-DRB1 allelic group, the most frequent was HLA-DRB1*03, with 17.03%. Comparison between these results and data from the Brazilian Bone Marrow Donor Registry (REDOME) showed that there were demographic and immunogenetic differences due to the history of immigration in the region of Ribeirão Preto, in southeastern Brazil. The results reinforce the importance of understanding the demographic and immunogenic profile of regions of Brazil, in order to reduce the waiting time for a histocompatible donor.

Donor-specific antibodies are associated with antibody-mediated rejection, acute cellular rejection, bronchiolitis obliterans syndrome, and cystic fibrosis after lung transplantation

Lung transplantation is limited by chronic lung allograft dysfunction. Acute cellular rejection (ACR) is a risk factor for allograft dysfunction; however, the role of antibody-mediated rejection (AMR) is not well characterized. This was a retrospective review from 2007 to 2011 of lung transplant recipients with human leukocyte antigen (HLA) antibody testing using Luminex (Luminex Corp, Austin, TX) single-antigen beads. Statistics included Fisher's exact test for significance. Donor-specific antibodies (DSA) developed in 13 of 44 patients. Of the 13 with DSA, 12 had cystic fibrosis compared with 18 of 31 in the non-DSA group (p = 0.035). Of those with DSAs, 23.1% occurred within the first year, and 69.2% occurred between 1 and 3 years. Twelve of 13 DSA patients had anti-HLA DQ specificity compared with 2 of 31 non-DSA patients (p = 0.0007). AMR developed in 10 of the 13 DSA patients compared with 1 of 31 non-DSA patients (p = 0.0001). The DSA group experienced 2.6 episodes/patient of cellular rejection vs 1.7 episodes/patient in the non-DSA group (p = 0.059). Bronchiolitis obliterans syndrome developed in 11 of 13 in the DSA group vs 10 of 31 in the non-DSA group (p = 0.0024). In the DSA group, 11.5% HLAs matched compared with 20.4% in the non-DSA group (p = 0.093). AMR developed in 11 of 22 patients in the non-DSA HLA group compared with 0 of 22 in the group without non-DSA HLA antibodies (p = 0.002). Survival at 1 and 3 years was 92% and 36% in the DSA group, respectively, and 97% and 65% in the non-DSA group. DSAs and non-DSAs occur frequently after lung transplantation. DSAs are prevalent in the cystic fibrosis population and are associated with AMR, bronchiolitis obliterans syndrome, and possibly, ACR.

‘Immunogenetics of Aging’: report on the activities of the 15th International HLA and Immunogenetics Working Group and 15th International HLA and Immunogenetics Workshop

'Immunogenetics of Aging' is a component that was first included in the 14th International HLA and Immunogenetics Workshop (IHIWS) and developed further within the 15th Workshop. The aim of this component was to assess the impact of human leukocyte antigen (HLA) genes, cytokine genes, and some innate immunity genes such as killer-cell immunoglobulin-like receptors (KIRs) and mannose-binding lectin 2 (MBL2) in successful aging and their contribution to the better understanding of immune dysfunction in old age. Within the 15th IHIWS new populations were included in the analysis. Additional cytokine gene polymorphisms were assessed and innate immunity genes were analyzed for possible relevance in longevity. The results showed that longevity might be associated with anti-inflammatory cytokine gene profiles, decreased frequency of interleukin-10 (IL-10) and transforming growth factor-B1 haplotypes associated with a low level of gene expression, and increased frequency of haplotypes determining a high level of expression. Extended tumor necrosis factor-A and IL-12B genotypes were also likely relevant to longevity. Data also showed that innate immunity genes are associated with susceptibility to infections in the elderly and showed that these genes might be an important genetic marker in aging. Decreased frequencies of KIR2DS5 and A1B10 haplotypes, and an increased proportion of MBL2-deficient haplotypes were found in the group with higher cytomegalovirus-specific IgG antibody levels. Together, these studies emphasize the relevance of genes regulating immune functions in maintaining human longevity and stress the importance of further clarifying their impact on successful aging.

High Impact of Human Leukocyte Antigen Matching On Overall Survival and Transplant Related Mortality in Allogeneic Hematopoietic Stem Cell Transplantation for CLL: Long-Term Study From the EBMT Registry.

Abstract 2286Poster Board II-263 Background:The outcomes of related and unrelated donor hematopoietic stem cell transplantations (HSCT) are strongly affected by the degree of human leukocyte antigen (HLA) matching between the transplant recipient and the donor or cord blood unit. HLA matching plays an important role in engraftment, incidence and severity of graft-versus-host disease (GVHD) and also in overall survival; although this factor is still not validated yet in many hematological malignancies. Objective:To evaluate the impact of HLA matching and difference in matching degree among transplants from unrelated donors (UD) on different outcomes in chronic lymphocytic leukemia (CLL). Materials & methods:We have analyzed 370 CLL patients who underwent an allogeneic HSCT reported to the EBMT registry. There were 280 males (75%) and 90 females with a median age of 53 years (24-69). Forty-five patients (12%) have received a previous HSCT. At transplant, 294 among 317 evaluated patients had a good performance status (PS) (93%), 43 patients were in CR (12%), 160 in PR (46%), 44 in SD (13%) and 103 in PD (29%) among 349 evaluated patients. Two hundred and sixty six patients received a reduced intensity conditioning regimen (RIC) and 103 a standard (Std) conditioning; 313 patients received PBSC, 56 BM and 2 cord blood cells from 198 HLA siblings, and 172 unrelated donors (UD). There were 136 (36%) sex-mismatched (91 F/M and 45 M/F), 150 pairs (40%) had an ABO incompatibility (61 minor, 89 major) and for CMV: 78 pairs were +, 146 - and 111 mixed. The median interval between diagnosis and transplantation was 53 months (3-308). According to the registry, there were 198 HLA siblings, 135 matched UD (MUD) and 37 mismatched UD (MMUD). We focused on UD and re-analyzed all HLA typings for patients and donors, after classification we found: 24 well matched (10/10 in high resolution), 28 partially matched (7/7, 8/8 or 9/9 in high resolution), 30 matched in low resolution and 90 mismatched in high resolution, which was different from the registry classification. Results:After transplantation, 359 patients engrafted, 199 developed an AGVHD (gr I: 74, gr II: 79, gr III: 29 and gr IV: 17) and 171 presented a cGVHD (83 limited and 88 extensive). The cumulative incidence of AGVHD for the total population was 22% for gr II and 13% for gr > II. [Siblings: 19% and 12%; well & patially matched: 37% and 10%; low resolution & MMUD: 19.6% and 15.3% for grII & gr > II respectively]. At 1 year after transplant for the total population, the cumulative incidence of limited and extensive cGVHD was 17 % (15-19) and 18.4% (16.4-20.4)[ Siblings: 16.2% (13.6-19) and 17.2% (14.5-20); well & patially matched: 23% (17.2-29) and 23.1% (17.2-29); low resolution & MMUD: 15.8% (12.3-19.1) and 18.3% (14.8-21.8)] respectively. With a median follow up of 48 months, the probability of 3 and 5-years overall survival (OS) for the total population were 62% (56-67) and 52% (45-57) respectively. We found a high significant difference in term of OS between the siblings, well & partially matched groups versus low & MMUD groups (p=0.002) (figure 2). [OS at 3 & 5 years; Siblings: 68.3% (61.8-75.5) and 57.2% (49.8-65.6); well & patially matched: 60.8% (47.6-77.7) and 53.3% (39.2-72.4), low resolution & MMUD: 49% (40.3-59.5) and 38.5% (29.5-50.2) respectively]. We observed also a high significant difference in term of transplant related mortality (TRM) between the same groups (p=0.0022) (figure 4). The multivariate analysis using Cox model studying age, pre-transplant status; gender, PS, cells source, ABO compatibility, conditioning and different HLA groups, showed a significant impact of 4 factors on OS: age: HR=1.04 (1.01-1.6) p=0.001, disease status (PD): HR=3.08 (1.2-7.1) p=0.02, PS: HR=2.37 (1.1-5.1) p=0.02 and HLA MMUD group: HR= 1.62 (1.02-2.59) p=0.03. The same factors were also highly significant in multivariate analysis in term of TRM (age: HR=1.04 (1.001-1.07) p=0.009, disease status (PD): HR=5.49 (1.29-23.4) p=0.02, PS: HR=3.8 (1.7-8.4) p=0.01 and HLA MMUD group: HR= 1.9 (1.07-3.37) p=0.02. Conclusion:This large retrospective analysis pointed out the high impact of HLA matching in terms of OS and TRM (in addition of age, disease status and PS), without any difference between HLA siblings, MUD and partially matched groups. Moreover, we demonstrated the importance of HLA classification when registering patients in the EBMT registry and its impact on different outcomes. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Artificial Antigen Presenting Cells (aAPC) Expanded NK-Mediated Enhanced Lysis of Allogeneic Tumor Cells Regardless of HLA Class I/KIR Mismatch and Its Implication of Use in Eradicating Acute Lymphoblastic Leukemia (ALL).

Abstract 3023Poster Board II-999NK Killer cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands play critical roles in maintaining natural killer (NK) cell tolerance, while providing surveillance against pathogens and malignant transformation. Natural killer (NK) cells have been explored as tools for adoptive anti-tumor or leukemia immunotherapy and current models hold that a mismatch or absence of KIR ligands on target cells is essential for efficient NK cell mediated cytolysis. However, new approaches are now available to activate NK cells and the role for KIR mediated signaling in regulating cytotoxicity of activated NK cells has not been well studied. In this study, aAPCs comprising IL15Ra+K562 cells engineered to express 4-1BBL activated and expanded peripheral NK cells in the presence of exogenous IL15 up to 1000-fold in 3 weeks. Compared to resting NK cells, 4-1BBL/IL15-activated NK cells upregulated TRAIL and NKp30, 44, 46 expression, and showed significantly enhanced cytotoxicity against a multitude of tumor targets including K562, Daudi, Ewing's tumors, osteosarcoma, as well as autologous tumors (50%-90% killing vs. 0%-8% with non-activated NK cells). Meanwhile we could detect little to no influence of KIR signaling in regulating cytotoxicity by aAPC activated NK cells, since sorted CD158a+ and CD158b+ activated NK cells showed similar killing of tumor cells expressing HLA group C1 (CD158b ligand) and/or C2 (CD158a ligand) antigens. In contrast, killer activating receptors (KARs) were indispensable for the cytolysis of solid pediatric tumors by aAPC-activated NK cells, since the killing was significantly inhibited by fusion proteins binding to the ligands of NKG2D, NK p30, p44, p46, p80 (KARs). About 20-40% inhibition of the killing was accomplished when all four activating receptors were blocked, though other activating receptors have not been well defined. Although acute lymphoblastic leukemia (ALL) blasts were refractory to fresh NK cytotoxicity, 4-1BBL/IL15 activated NK cells demonstrated higher lytic activities (20%-50%) against ALL blasts from either patients or cell lines. ALL blast lysis could be completely or partially inhibited by KAR-blocking fusion proteins, indicating that expression levels of KAR ligands vary among ALL cases and other solid tumors. We conclude that KIR ligand mismatch or absence is not essential for effective NK cytotoxicities on either solid tumors or ALL when fully activated NK cells are utilized. This suggests that adoptive therapy with autologous aAPC-activated NK cells may prove effective in some clinical settings, such as ALL, AML, or certain solid tumors. Further studies to assess the impact of KAR ligand expression on aAPC-activated NK killing of ALL blasts are in progress.Percentage of Activated NK Killings vs. Fresh NK's with/without KAR-Ig Fusion ProteinsActivated NK (E:T=2.5:1)Fresh NK (E:T=25:1)-KAR-Ig Fc+KAR-Ig FcSB tumor (Ewing's)48%30%0.5%HOS (Osteo sarcoma)63%36%0.7%Daudi (B. lymphoma)78%46%0.2%REH (ALL)54%8%3% DisclosuresNo relevant conflicts of interest to declare.

Is there any relationship between human leucocyte antigen class II and chronic urticaria? (chronic urticaria and HLA class II).

The Human Leukocyte Antigen (HLA) typing of large groups of patients with various autoimmune diseases has demonstrated that some HLA alleles occur at higher frequencies in specific diseases than in the general population. Chronic urticaria has been shown to have an autoimmune basis by a previous study which found an association between chronic urticaria and specific HLA groups. We investigated the HLA subtypes of Turkish chronic urticaria patients. For this purpose 42 Turkish patients with chronic urticaria and 115 healthy controls were typed for HLA-DR and DQ by PCR-SSP (Polymerase Chain Reaction Sequence Specific Primers) low resolution DNA technique. We found an increased frequency of DR4 (42.9%, p=0.01) in chronic urticaria patients in comparison with that in healthy controls. This study supports the hypothesis that HLA alleles may be involved in the pathogenesis of chronic urticaria and that they appear to be directly involved in the initiation of the immune response.