HLA-DQ Typing Research Articles

Re-exploring the iceberg of celiac disease in children: Results of a multicenter Italian screening project, based on a rapid HLA DQ typing test

Objectives: We aimed to assess the prevalence of celiac disease (CD) autoimmunity and overt CD in school age Italian children by using HLA typing as the initial test and to redefine the clinical spectrum of CD.

Re-exploring the iceberg of celiac disease in children: Preliminary results of a multicenter Italian screening project based on a rapid HLA DQ typing test

Re-exploring the iceberg of celiac disease in children: Preliminary results of a multicenter Italian screening project based on a rapid HLA DQ typing test

P100 Resistance to BK Viremia in renal transplant patients is associated with HLA-DQ5 and HLA-DQ6

Aim BK Viremia (BKV) and subsequent BK nephropathy are associated with renal graft loss. We hypothesized that the presence or absence of certain HLA allele(s) increases the susceptibility to BKV reactivation in renal transplant recipients on chronic immunosuppression. In a previous study, we compared 94 BKV+ patients and 682 normal bone marrow donors using our HLA Epitope Analysis Program that can detect every possible HLA epitope of 1–4 amino acids in the peptide-binding groove. The DQB1 epitope, EV—RGI84–90, (common to DQ5/6) was found to be significantly associated with resistance (p = 0.028). The HLA-DQB1 epitope, QLELRTT84–90, (common to DQ2/3/4) was associated with BK susceptibility (p = 0.02). Methods In this study, we used renal transplant patients who did not develop BKV as the controls to determine if HLA-DQ5/6 would remain associated with BKV resistance. Renal patients who had received a single transplant were analyzed for BKV and HLA-DQ typing. The typing of the recipient was used to separate the BKV+ and BKV− patients into three groups: homozygous for DQ5/6, heterozygous for DQ5/6 and DQ2/3/4 or homozygous for DQ2/3/4. Results Renal transplant recipients homozygous for DQ2/3/4 had a greater risk for disease than those homozygous for DQ5/6 (OR = 2.16 vs OR = 0.724). Patients who were heterozygous were also resistant to disease (OR = 0.508). The HLA typing of the donor was analyzed in the same manner but was not found to be significantly associated with BKV susceptibility. Conclusions The presence of a DQ5/6 allele is dominant resistant to BKV suggesting presentation of BK peptides on DQ5/6 to T cells may be required to prevent BK virus reactivation. Download : Download high-res image (99KB) Download : Download full-size image

P146 The use of surrogate crossmatching allows for the detection of a possible donor specific antibody to an HLA-DQ heterodimer

Aim The development of de novo donor-specific antibodies (DSA) post-transplant is an area of interest for the transplant community. There are several challenges in detecting DSA, including the use of recombinant HLA antigens vs. affinity-purified antigens from a phenotype, and the lack of donor typing at many loci. Herein, we describe a case where surrogate flow-cytometric crossmatch (FCXM) was used in conjunction with solid-phase immunoassays for the detection of DSA in a heart transplant recipient. Methods Post-transplant serum was tested by solid-phase immunoassays for the detection of DSA to the following donor antigens: A2,23; B7,8; Bw6; Cw7; DR15,17; DR52; DQ2,6. Confirmation of antibody specificity was obtained using FCXM using three surrogate donor cells. Results Initial testing by One Lambda LABScreen® PRA and Single Antigen assays provided negative results for HLA class I, and inconclusive results for HLA class II, suggesting possible reactivity to HLA-DQ2, HLA-DQA1∗05:01/DQB1∗02:01, or false-positive reactivity. In order to confirm the possible specificities obtained, surrogate crossmatching was performed utilizing pronased cells from donors with the following HLA types: Donor 1- DQB1∗02:XX, 03:XX (DQ9); DQA1∗02:01; Donor 2- DQB1∗02:01; DQA1∗05:01; Donor 3- DQB1∗02:01, 03:01 (DQ7); DQA1∗05:01, with recipient serum at dilutions of Neat, 1:2, 1:4, and 1:16. T cell crossmatch results at all dilutions were negative for each donor cell tested. Donor 1 tested B cell negative at all dilutions tested, while donor 2 tested positive at serum dilutions of Neat, 1:2, and 1:4, and donor 3 tested positive at serum dilutions of Neat and 1:2. This evidence allowed for us to assign a strong antibody, defined by our laboratory as predicted to yield a positive FCXM, to the DQA1∗05:01/DQB1∗02:01 heterodimer. Since donor HLA-DQA1 typing was not available, it is inconclusive whether the antibody detected should be considered donor-specific. Conclusion We conclude that while solid-phase immunoassays are useful tools for the detection of HLA antibodies, there are several challenges present which could require the use of additional assays for confirmation of test results. In addition, the lack of complete donor typing often makes it difficult for the laboratory to accurately interpret the findings of such results.

A Rare HLA-DRB1*14:22-DQB1*04:01 Haplotype in a Kidney Donor: Implication in the Interpretation of Donor-Specific Antibody in Kidney Transplantation—A Case Report

BackgroundThe presence of donor-specific human leukocyte antigen antibodies (HLA-DSA) can be determined by performing Luminex assay with single-antigen beads. The single-antigen beads' panels cover the most frequent HLA alleles of the HLA-A, B, C, DRB1, DRB3/4/5, DQB, and DP loci, although the HLA typing for deceased donors often includes only HLA-A, B, and DR. Therefore, the information of haplotypic association between DRB1 and DQB1 is essential for the analysis of HLA-DSA, especially when HLA-DQ antibodies are identified in the patient's serum. Case ReportWe report the finding of a rare HLA-DRB1*14:22-DQB1*04:01 haplotype in a Thai potential kidney donor. HLA class I and class II high-resolution typing were performed by a method of polymerase chain reaction with the use of sequence-specific primers. The HLA-A*24:02-C*04:06-B*13:01-DRB3*02:02-DRB1*14:22-DQA1*05:05-DQB1*04:01 haplotype in the kidney donor was confirmed by segregation analysis in the kidney donor's family. This rare haplotype was also identified in her father and the 2 of her offspring. ConclusionsTo our knowledge, this is the 1st report of the rare HLA-DRB1*14:22-DQB1*04:01 haplotype in Thai individuals. The information of the rare HLA-DR-DQ haplotypic association provides a caution for HLA laboratory personnel when analyzing HLA-DSA in a patient with HLA-DQ antibodies and the HLA-DQ typing of a deceased donor is unavailable.

Prevalence of Autoantibodies and HLA DR, DQ in Type 1 Diabetes Mellitus.

Type I diabetes Mellitus (T1DM) is caused by autoimmune destruction of β-cells of pancreas. Two forms of T1DM are known called as 1A (autoimmune) and 1B (idiopathic). Aim was to study the prevalence of Anti-TTG IgA, Anti-TPO, GADA, ZnT8 and IA-2 autoantibodies and HLA DR and DQ genes and its diagnostic value in T1DM. Thirty four T1DM patients, 59 type 2 diabetes mellitus (T2DM) patients and 28 healthy controls were included in study. Antibodies levels were estimated by ELISA and HLA typing was performed by SSP-PCR method. The prevalence of various autoantibodies in T1DM were Anti-TTG 14.7%, Anti-TPO 17.65%, GADA 38.23%, ZnT8 11.76% and IA-2 5.88%. Only GADA and ZnT8 were significantly positive in T1DM. GADA (66.67%) and ZnT8 (33.33%) positivity was more in patients below 15 years age while levels of other antibodies were higher after 15 years age. All autoantibodies were detected in higher frequency in T1DM than in T2DM and controls. HLA DR and DQ typing showed highly significant increase in DRB1*0301 (61.76%, p=0.00) and DQB1*0201 (64.71%, p=0.00) in T1DM. Subjects with HLA DRB1*0301 and DQB1*0201 had 80-100% positive prevalence of GADA, ZnT8, IA-2, Anti-TTG and Anti-TPO autoantibodies. Combination of GADA antibody with DRB1 and DQB1 estimation improved diagnosis of T1A than insulin antigen specific antibodies alone.

Valor predictivo y utilidad clínica del genotipado HLA-DQ en el diagnóstico de la enfermedad celiaca en mayores de 50 años

IntroductionCeliac disease is significantly undiagnosed, especially in older individuals. The aim of this study is to determine the predictive value of HLA-DQ typing in the diagnosis of celiac disease in patients over 50 and analyze the possible relationship between the gradation of risk attributed to the alleles and diagnosis in elderly. Materials and methods635 patients were studied during 2013 with suggestive symptoms of celiac disease. The diagnosis was confirmed by serologic studies and small bowel biopsy. The HLA-DQ genotyping was performed using a PCR-SSOP technique. Results68 of out 635 patients studied (10.7%) were older than 50 years with a male to female ratio of 1:3. The frequency of the alleles that has been associated with risk of CD (HLA DQ2.5 and/or HLA DQ8) was 87.5% (56 patients), being celiac 13 of them. 21 patients carry the half allele of HLA-DQ2.5 (DQA1*05 or DQB1*02) associated with low risk of celiac disease being none of them celiac. One patient with celiac disease did not carry DQ2.5 or DQ8 heterodimers but was positive for serological and histological analysis. The positive predictive value of the use of HLA testing in the population older than 50 years is 29.27% and the negative predictive value is 93%. ConclusionsDue to the high negative predictive value, the determination of HLA-DQ is a useful marker in the diagnosis of CD, in individuals over 50 with associated clinical. There was no relationship between low risk alleles and late onset of disease.

HLA - DQ genotyping in celiac disease in western India.

Very few human leukocyte antigen (HLA) studies have been carried out in celiac disease patients in India. The aim was to study the HLA DQ antigens in diagnosed celiac disease patients. The cross sectional study analysed non-consecutive 34 celiac patients diagnosed as per modified ESPGHAN criteria at tertiary centre and compared with 25 controls. The HLA-DQ typing was carried out using Histo Spot SSO HLA DQ celiac disease kit by tissue typing department. Out of 34 celiac disease patients (26 females, age ± SD 38.79 ± 15.84 years), 59% presented with typical diarrheal disease. Anemia (76%) was most common extra intestinal manifestation followed by bone pain (53%), neurological (12%) and infertility (3%). All 34 patients were IgA antiendomysial antibody positive out of which 32 patients (94%) were HLA-DQ positive (31 patients were HLA-DQ 2 and 1 was HLA-DQ 8 positive).Among HLA positive patients 13, 9 and 10 patients had modified Marsh stage 1, 2 and 3 respectively. HLA DQ 2 and DQ8 positivity among celiac patients (94%) was statistically significant as compared to controls (12%) (P< 0.0001). HLA DQ 2.5 (DQA1*0501 :DQB1*0201 haplotype) and DQ 2 (DQB1*02) haplotypes were common accounting for 70% of patients followed by DQ X.5, DQ8 and DQ 2.2. Celiac disease in Indian patients is predominantly associated with HLA DQ 2 and DQ 8 genotype and has high positive predictive value for diagnosis when combined with serology in symptomatic patients.

Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study.

BackgroundNon-celiac gluten sensitivity (NCGS) or ‘wheat sensitivity’ (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics.MethodsThis prospective observation study included 75 NCWS patients (63 women; median age 36 years) with irritable bowel syndrome (IBS)-like symptoms, 65 IBS and 50 celiac controls. Patients were recruited at two Internal Medicine Departments. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, HLA DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake.ResultsDBPC cow's milk proteins challenge showed that 30 of the 75 NCWS patients suffered from multiple food sensitivity. Osteopenia and osteoporosis frequency increased from IBS to NCWS and to celiac disease (CD) (P <0.0001). Thirty-five NCWS patients (46.6%) showed osteopenia or osteoporosis. Low BMD was related to low BMI and multiple food sensitivity. Values of daily dietary calcium intake in NCWS patients were significantly lower than in IBS controls.ConclusionsAn elevated frequency of bone mass loss in NCWS patients was found; this was related to low BMI and was more frequent in patients with NCWS associated with other food sensitivity. A low daily intake of dietary calcium was observed in patients with NCWS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-014-0230-2) contains supplementary material, which is available to authorized users.

Immunogenetics of non celiac gluten sensitivity.

The immunogenetics of coeliac disease (CD) has advanced from “Bench to Bed” in the sense that HLA-DQ typing is now an established part of the diagnostic armamentarium. The configuration characteristics and the specificity of the HLA-DQ2, (1) -DQ8 (2, 3) and –DQ9 (4, 5) allow the binding of small peptides that cannot be further digested by the absence of specific human intestinal enzymes (6, 7). These peptides are derived from wheat (gliadins and glutenins), barley (hordeins), rye (secalins), oats (avenines) and hybrids of these grains, such as kamut and triticale and bind to HLA molecules, in

Risk of low bone mineral density and low body mass index in patients with non-celiac wheat-sensitivity: a prospective observation study

Non-celiac gluten sensitivity (NCGS) or ‘wheat sensitivity’ (NCWS) is included in the spectrum of gluten-related disorders. No data are available on the prevalence of low bone mass density (BMD) in NCWS. Our study aims to evaluate the prevalence of low BMD in NCWS patients and search for correlations with other clinical characteristics. This prospective observation study included 75 NCWS patients (63 women; median age 36 years) with irritable bowel syndrome (IBS)-like symptoms, 65 IBS and 50 celiac controls. Patients were recruited at two Internal Medicine Departments. Elimination diet and double-blind placebo controlled (DBPC) wheat challenge proved the NCWS diagnosis. All subjects underwent BMD assessment by Dual Energy X-Ray Absorptiometry (DXA), duodenal histology, HLA DQ typing, body mass index (BMI) evaluation and assessment for daily calcium intake. DBPC cow's milk proteins challenge showed that 30 of the 75 NCWS patients suffered from multiple food sensitivity. Osteopenia and osteoporosis frequency increased from IBS to NCWS and to celiac disease (CD) (P <0.0001). Thirty-five NCWS patients (46.6%) showed osteopenia or osteoporosis. Low BMD was related to low BMI and multiple food sensitivity. Values of daily dietary calcium intake in NCWS patients were significantly lower than in IBS controls. An elevated frequency of bone mass loss in NCWS patients was found; this was related to low BMI and was more frequent in patients with NCWS associated with other food sensitivity. A low daily intake of dietary calcium was observed in patients with NCWS.

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To investigate the correlation of HLA alloepitopes with the development of de novo donor specific antibodies ( dn DSA) after renal transplantation. High resolution HLA-DR and HLA-DQ typing of 31 recipients with dn DSA and their donors was performed using sequence specific oligonucleotide probes. HLAmatchmaker software was used to determine eplet mismatches (MM). The mismatched eplet load for donor recipient pairs and the immunodominance of each eplet MM was analyzed. Dn DSA developed against HLA-DR (n = 14), HLA-DQ (n = 22), or both (n = 5). Mean traditional HLA antigen mismatch was not predictive of dn DSA development at HLA-DR (1.1 MM vs. 1.4 MM, p = 0.36) (Fig. 1) or HLA-DQ alpha/beta (1.6 MM vs. 2.2 MM, p = 0.06). However, those who developed dn DSA had a greater number of locus specific mismatched eplets at HLA-DR (11.2 MM vs. 17.4 MM, p = 0.05) and HLA-DQ (7.3 MM vs. 26 MM, p < 0.01). There were 5 HLA-DR eplets and 19 HLA-DQ (alpha chain n = 9, beta chain n = 10) (Fig. 2) eplets which were significant univariate predictors of dn DSA development against HLA-DR or HLA-DQ respectively. Eplet load was a better predictor of dn DSA development compared to traditional HLA matching at the Class II HLA-DR and HLA-DQ loci. Further study will be needed to evaluate whether these immunodominant epitopes predict dn DSA development in a multivariate model.

IgA antibodies against deamidated gliadin peptides in patients with chronic liver diseases

Background/aimsIgA antibodies against tissue-transglutaminase (anti-tTG-IgA) and IgA and IgG antibodies against deamidated gliadin peptides (anti-DGP-IgA and anti-DGP-IgG) are considered specific for celiac disease (CD) whereas, patients with chronic liver disorders have an increased risk of latent CD development. We investigated the prevalence and clinical significance of anti-DGP-IgA, anti-DGP-IgG and anti-tTG-IgA in a large cohort of patients with chronic liver diseases. Methods668 patients without gastrointestinal symptoms (426 viral hepatitis, 94 autoimmune liver diseases, 61 alcoholic disease, 46 non-alcoholic fatty liver disease, 41 with other liver disorders) were investigated by ELISAs (INOVA Diagnostics). Patients positive for at least one autoantibody invited for a small-intestinal biopsy and HLA-DQ typing. ResultsAnti-DGP-IgA were detected in 8.5%, anti-DGP-IgG in only one (0.15%, P<0.001) and anti-tTG-IgA in 5.8% of patients (P=0.05). Fifty-two were anti-DGP-IgA(+)/anti-tTG-IgA(−), 34 anti-DGP-IgA(−)/anti-tTG-IgA(+), and 5 anti-DGP-IgA(+)/anti-tTG-IgA(+). Anti-DGP-IgA positivity was associated with older age (P<0.05), cirrhosis (P<0.05) and increased IgA (P<0.05) whereas, anti-tTG-IgA only with cirrhosis (P<0.05). Histology and HLA-typing compatible with CD was revealed in 4/14 anti-DGP-IgA(+)/anti-tTG-IgA(−), 0/13 anti-DGP-IgA(−)/anti-tTG-IgA(+) and 2/2 anti-DGP-IgA(+)/anti-tTG-IgA(+). All 6 patients diagnosed with CD were anti-DGP-IgA(+) and only 2 anti-tTG-IgA(+). ConclusionsAlthough a significant number of patients had detectable CD-related autoantibodies, anti-DGP-IgA test seems better than anti-tTG-IgA for unmasking occult forms of CD in patients with chronic liver disorders. The known good performance for CD diagnosis of anti-DGP-IgG test was not confirmed in this specific group of patients.

HLA-DQ typing in the diagnostic algorithm of celiac disease

celiac disease (CD) is an immune-mediated chronic inflammatory disease associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD diagnostic algorithm in order to contribute to the development of practical indications for the use of HLA typing. we selected 317 subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were included in the study; a control sample of 70 healthy individuals was recruited. 64% of patients with CD carried DQ2 heterodimer (α5β2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed β2 chain and 1.1% were positive for DQ2 α5 chain. The only presence of α5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between β2 chain and CD. In the case-control study we observed a progression of increased risk, ranging from 1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6% of first degree family members were affected, exclusively in presence of HLA-DQ2, -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than parents. Finally, considering the different patterns of clinical presentation among the HLA-DQ risk classes identified we found no relationship between CD clinical presentation and HLA-DQ risk categories. our results strengthen the evidence that HLA-DQ status strongly influences the development of CD and demonstrate that knowledge of a patient's HLA-DQ genotype allows to establish clinically relevant genetic risk profiles.

Cystic fibrosis is a risk factor for celiac disease.

The coexistence of cystic fibrosis (CF) and celiac disease (CD) has been reported. To our knowledge there is no study directly comparing the incidence of CD in CF patients to that in the general population at the same time. There is no published data on genetic predisposition to CD in CF patients either. Therefore, in the present study we aimed to assess the genetic predisposition to CD and its incidence in CF patients comparing it to data from the general population. Two hundred eighty-two CF patients were enrolled in the study. In 230 CF patients the genetic predisposition to CD (the presence of HLA-DQ2/ DQ8) was assessed. In all CF patients, serological screening for CD was conducted. In patients with positive antiendomysial antibodies (EMA) gastroduenoscopy was offered. Intestinal histology was classified according to modified Marsh criteria. The results of serological CD screening in 3235 Polish schoolchildren and HLA-DQ typing in 200 healthy subjects (HS) were used for comparison. Positive EMA was found in 2.84% of the studied CF patients. The incidence of proven CD was 2.13%. The incidence of CD as well as positive serological screening were significantly more frequent in the CF group than in the general population. The frequency of CD-related HLA-DQ alleles in CF and HS did not differ. Genetic predisposition to celiac disease in cystic fibrosis patients is similar to that of the general population. However, our results suggest that cystic fibrosis is a risk factor for celiac disease development.

M2032 HLA-DQ Typing of Extra-Intestinal T-Cell Lymphomas: Evidence for An Association with Undiagnosed Celiac Disease? a Pilot Study On Anaplastic Large Cell Lymphomas

Introduction: The prevalence of celiac disease (CD) is 0.5-1% in the Western population. As CD is widely underdiagnosed, the majority of CD patients is still untreated and therefore at greater risk of developing complicated CD, including Enteropathy Associated T-cell Lymphoma (EATL). Differentiation between various T-cell lymphomas is difficult because of similar morphology and immunophenotype. The final diagnosis is based on clinical presentation and localisation of the lymphoma. Consequently, T-cell lymphomas in CD patients and T-cell lymphomas in the small bowel are always diagnosed as EATLs. However, 25% of EATLs are located extra-intestinal. The most frequent type of T-cell lymphomas is anaplastic large cell lymphoma (ALCL). ALCLs are either anaplastic lymphoma kinase (ALK) negative or positive. EATLs are always ALK negative. As is the case for most EATLs, ALCLs are CD30 positive. CD and EATL are strongly associated with HLA-DQ2 and/or -DQ8. HLADQ2 and/or -DQ8 expression is found in 98% of CD and EATL patients, compared to 40% in the Western population. Aims and Methods: We investigated whether the frequency of HLA-DQ2 and/or -DQ8 is increased in extra-intestinal ALCLs compared to the general population, in order to determine if extra-intestinal ALCLs might in fact be undiagnosed EATLs. For this purpose, extra-intestinal ALCL samples, ALK-positive and ALK-negative, were collected and DNA was isolated. DQA1 and DQB1 alleles were amplified using PCR. HLA-DQ typing was subsequently performed using a single strand conformation polymorphism / heteroduplex based method (SSCP/HD). Results: So far, 21 anaplastic large-cell lymphomas have been HLA-DQ typed. HLA-DQ2 was present in 10 lymphomas, of which 3 were homozygous. HLA-DQ8 was present in 4 lymphomas, all heterozygous. In total, twelve lymphomas (57%) were HLA-DQ2 and/or -DQ8 positive, indicating only a slightly higher prevalence than in the general population. However, within the subgroup of ALKnegative ALCLs, representing potentially undiagnosed EATLs, 71% was HLA-DQ2 and/or DQ8 positive (p=0.05). Conclusion: The increased prevalence of HLA-DQ2 and/or -DQ8 in ALK-negative ALCLs suggests underdiagnosis of EATL within this group of extra-intestinal T-cell lymphomas.

M2033 Role of Antibodies in the Long Term Follow Up of Patients with Celiac Disease to Predict the Adherence to Gluten-Free Diet

Introduction: The prevalence of celiac disease (CD) is 0.5-1% in the Western population. As CD is widely underdiagnosed, the majority of CD patients is still untreated and therefore at greater risk of developing complicated CD, including Enteropathy Associated T-cell Lymphoma (EATL). Differentiation between various T-cell lymphomas is difficult because of similar morphology and immunophenotype. The final diagnosis is based on clinical presentation and localisation of the lymphoma. Consequently, T-cell lymphomas in CD patients and T-cell lymphomas in the small bowel are always diagnosed as EATLs. However, 25% of EATLs are located extra-intestinal. The most frequent type of T-cell lymphomas is anaplastic large cell lymphoma (ALCL). ALCLs are either anaplastic lymphoma kinase (ALK) negative or positive. EATLs are always ALK negative. As is the case for most EATLs, ALCLs are CD30 positive. CD and EATL are strongly associated with HLA-DQ2 and/or -DQ8. HLADQ2 and/or -DQ8 expression is found in 98% of CD and EATL patients, compared to 40% in the Western population. Aims and Methods: We investigated whether the frequency of HLA-DQ2 and/or -DQ8 is increased in extra-intestinal ALCLs compared to the general population, in order to determine if extra-intestinal ALCLs might in fact be undiagnosed EATLs. For this purpose, extra-intestinal ALCL samples, ALK-positive and ALK-negative, were collected and DNA was isolated. DQA1 and DQB1 alleles were amplified using PCR. HLA-DQ typing was subsequently performed using a single strand conformation polymorphism / heteroduplex based method (SSCP/HD). Results: So far, 21 anaplastic large-cell lymphomas have been HLA-DQ typed. HLA-DQ2 was present in 10 lymphomas, of which 3 were homozygous. HLA-DQ8 was present in 4 lymphomas, all heterozygous. In total, twelve lymphomas (57%) were HLA-DQ2 and/or -DQ8 positive, indicating only a slightly higher prevalence than in the general population. However, within the subgroup of ALKnegative ALCLs, representing potentially undiagnosed EATLs, 71% was HLA-DQ2 and/or DQ8 positive (p=0.05). Conclusion: The increased prevalence of HLA-DQ2 and/or -DQ8 in ALK-negative ALCLs suggests underdiagnosis of EATL within this group of extra-intestinal T-cell lymphomas.

Persistent elevated tissue‐transglutaminase in cystic fibrosis

Persistent elevated tissue‐transglutaminase in cystic fibrosis

Anti-centromere antibodies (ACA) in systemic sclerosis patients and their relatives: a serological and HLA study.

Autoantibody reactivity to centromere proteins CENP-A, CENP-B and CENP-C was examined in 58 patients with systemic sclerosis (SSc), 218 first degree relatives and 22 spouses. HLA class II typing for HLA-DRB1 and HLA-DQA1 was performed by restriction fragment length polymorphism (RFLP) analysis in 50 families, and HLA-DRB1, HLA-DQA1 and HLA-DQB1 typing was performed by olignucleotide typing in 44 families. Eleven probands and two relatives had ACA. The two relatives with ACA also had SSc. One relative was an identical twin sister of a proband with ACA and the other relative was a sister of a proband with ACA. All ACA-positive probands and relatives were female, and all recognized CENP-A, CENP-B and CENP-C. The presence of at least one HLA-DQB1 allele not coding for leucine at position 26 of the first domain appeared necessary, although not sufficient for the generation of ACA. Therefore within SSc families ACA is strongly associated with female gender and disease phenotype, and is at least in part genetically determined.

HLA-DR17 and Mooren’s ulcer in South India

Objective:To investigate the association between Mooren’s ulcer and human leucocyte antigen (HLA) type DR17(3) in patients from the Tamil Nadu State of South India.Methods:Blood samples from 38 patients with Mooren’s...