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PubMed1977

Idiopathic hemochromatosis. Demonstration of recessive transmission and early detection by family HLA typing.

We studied iron overloading and HLA types in 24 sibships of patients with idiopathic hemochromatosis, of which 15 had at least two subjects with overt forms. HLA types of 84 unrelated patients were also investigated. Among siblings there was a significant association (P less than 0.0001) between the presence of hemochromatosis and the possession of the same two HLA haplotypes. The fact that overt forms of hemochromatosis depend on the presence of two specific homologous chromosomes strongly supports a recessive mode of transmission for the overt disease. The haplotypic equilibrium demonstrated in the unrelated patients group is another supporting argument. The lod-score value (2.239 for theta = 0.005) in six families available for study further supports the conclusion that a hemochromatosis gene is closely linked to the HLA-A locus. HLA typing in families with hemochromatosis could provide a means of early detection of subjects at risk before appearance of any sign of iron overload.

Adult↗

PubMed1991

DNA amplification for DQ typing as an adjunct to serological prenatal HLA typing for the identification of potential donors for umbilical cord blood transplantation.

It has recently been demonstrated that umbilical cord blood from genotypically human leukocyte antigen (HLA)-matched donors can provide sufficient numbers of progenitor cells for hematopoietic reconstitution. This technique has been successfully applied in the treatment of two children affected with Fanconi anemia (FA). Fetal cells from the potential sibling donors were first tested to determine that the fetus was not affected with FA. Unaffected fetal cells were then tested for HLA type. Cord blood from compatible donors can be harvested at birth and used immediately or frozen for subsequent use in hematopoietic reconstitution. We now show that fetal cell DNA amplification and hybridization for DQ typing can be an important adjunct procedure to verify serologically determined HLA class II types and/or to establish class II haplotype identity with the affected sibling.

Blood Transfusion↗

PubMed1999

Thyroid autoimmunity in children and adolescents with type 1 diabetes mellitus. Effect of age, gender and HLA type.

Type 1 diabetes is often associated with additional autoimmune phenomena. However, data reported on the frequency of thyroid autoimmunity differ vastly. Therefore, the prevalence of thyroid autoantibodies was evaluated at a large pediatric diabetes center in Southern Germany. 2,305 determinations (TPO and TG, ELISA) were performed in 495 patients with type 1 diabetes (234 boys, 261 girls; age at last measurement: 15.4 +/- 0.3 years, duration of diabetes 7. 5 +/- 0.2 years). The prevalence of elevated thyroid antibodies increased dramatically with age: from 3.7% in patients less than 5 years of age up to 25.3% in the age group 15-20 years (p < 0.0001). For children older than 10 years, girls were significantly more affected than boys (p < 0.0001). Thyroid autoimmunity tended to be more prevalent in the subgroup of patients with the HLA type DR3/DR4 compared to patients with other HLA types (p = 0.08). In children older than 10 years, basal TSH concentrations were significantly elevated in antibody-positive patients (p < 0.05). In conclusion, thyroid autoimmunity is prevalent in children and adolescents with type 1 diabetes. Adolescent girls and young women are especially affected. Yearly routine determinations of thyroid antibodies are therefore recommended.

Adolescent↗

PubMed1977

HLA typing of leukemic cells and lymphoblastoid cell lines: effects of non-HLA antibodies in common typing sera.

Several laboratories have recently observed that common HLA typing sera contain antibodies to various nonHLA antigens, including leukemia-associated antigens and normal platelet, granulocyte, or B-lymphocyte-specific alloantigens. In order to study the possible effects of these antibodies on HLA typing data in leukemia, several of these sera were adsorbed with HLA typed platelets, purified B-lymphocytes, cultured lymphoblasts, or mononuclear cells from patients with active leukemia of various types, and retested for residual activity against previously reacting cells. The results indicate that many of the reactions of leukemia cells to HLA typing sera represent reactions to nonHLA antibodies, many of which are directed against antigens common to cultured lymphoblasts, leukemia cells of several types, and normal B-cells. In the absence of family studies or prior serum adsorption, caution should be used in interpretation of all data related to HLA antigens in leukemia.

Antibodies↗

PubMed1984

HLA typing of dried sperm.

HLA human histocompatibility leukocyte antigens -A and -B antigens are expressed on human spermatozoa. A micro- and a macro-technique are described to HLA-type dried sperm coming from unknown subjects. The high HLA genetic polymorphism allows a high degree of sperm individualization which may be of value to blame or discard suspects in forensic science cases.

HLA Antigens↗

PubMed2002

[The application of molecular biology techniques in HLA-typing].

Human leukocyte antigen (HLA) is an important immunogenetic system. It plays a key role in immunoresponsiveness and hematopoietic stem cell and organ transplantation. The development of modern medicine and tissue typing promotes the combination of molecular biology techniques with HLA typing, and improves the accuracy and practicability of HLA typing. In this review, recent advances were concisely introduced in research of HLA typing on the application of restriction fragment length polymorphism (RFLP), sequence specific oligonucleotide probe (SSOP), single strand conformational polymorphism (SSCP), sequence specific primer (SSP), flow cytometry, gene chip, sequencing based typing, virtual DNA analysis and so on.

DNA↗

PubMed1976

HLA typing.

I present an overview of HLA typing, a method of evaluating donor-recipient compatibility. The major histocompatibility system in man, the HLA region, considered to control the immunologic response to transplantation and perhaps to certain diseases, is discussed in relation to chromosomal location, chromosomal mapping, association with other markers, nomenclature of the gene products (the HLA antigens), inheritance of the HLA antigens, and methods of determining these antigens. Use of HLA typing is currently most applicable in the correlation of certain diseases with HLA antigen frequency, in evaluating donor-recipient pairs for renal and bone marrow transplantation and for transfusion of platelets and granulocytes and in paternity testing.

Animals↗

PubMed2026

FuFiHLA: a tool for full-field HLA typing from long-read data.

MOTIVATION: Allele typing for Human Leukocyte Antigen (HLA) genes has many important clinical applications. Popular short-read typing can only accurately distinguish alleles at the coding sequence level, which potentially limit our understanding of the effect of variants in non-coding region. Long read data has been proved to be useful in typing HLA alleles in full resolution, but only a few tools are publicly available and with significant limitations in practical application. RESULTS: We developed FuFiHLA, a lightweight open-source software, to type HLA alleles. Currently it supports typing alleles of six HLA genes (HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, and HLA-DQB1) from long reads. Evaluation using 233 PacBio HiFi WGS samples from HPRC shows that FuFiHLA achieves 99.6% accuracy in the full field allele typing and QV as 51.8 for consensus allele sequence construction. Additional testing on four Nanopore R10 reads demonstrates slightly reduced accuracy in the fourth field. AVAILABILITY: FuFiHLA is available at https://github.com/jingqing-hu/FuFiHLA under MIT License.

Humans↗

PubMed2005

Use of HLA typing in diagnosing celiac disease in patients with type 1 diabetes.

OBJECTIVE: This study examines the use of HLA typing for the diagnosis of celiac disease in a group of Australians with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects included 131 sequential patients with type 1 diabetes (mean age 17 years [range 10-37]), 77 patients with biopsy-proven celiac disease (mean age 52 years [range 12-84]), and 162 healthy control subjects (mean age 17 years [range 2 months to 56 years]). Subjects were prospectively screened for celiac disease using endomysial antibodies (EMAs), tissue transglutaminase antibodies (TTGAs), and celiac disease-specific HLA typing. RESULTS: Celiac disease was diagnosed in 11 subjects after an intestinal biopsy (prevalence 8.4%). There was 95% agreement between TTGA and EMA for positive results and 100% for negative results. There was no significant difference for HLA DQ2 and DR4 among patients with type 1 diabetes with or without celiac disease. CONCLUSIONS: The prevalence of celiac disease among patients with type 1 diabetes is higher than previously estimated in Australia. TTGA is a valuable diagnostic tool that can be used for screening celiac disease in patients with type 1 diabetes. HLA typing should not be used in the diagnosis of celiac disease in patients with type 1 diabetes because of the similarities of HLA types between patients with type 1 diabetes and those with celiac disease.

Adolescent↗

PubMed1986

Antigen specific immune response potential and HLA typing of Israeli patients with thyroid autoimmune diseases (TAD).

The immune response potential to the synthetic polypeptide antigen (T,G)-A--L was studied in 35 patients with thyroid autoimmune diseases (TAD). For this purpose the ability of their antigen activated peripheral blood lymphocytes (PBL) to generate a (T,G)-A--L specific helper factor was tested. In addition, the patients were typed for their HLA determinants. The results of the study have shown that 20/35 (57%) patients responded to (T,G)-A--L, a similar proportion to that found among healthy donors that were tested as control. No significant difference was found in the rate of responses between patients with Graves' disease and Hashimoto's thyroiditis. The responses in these groups of patients were shown to be 13/22 (59%) and 7/13 (54%) respectively. HLA typing of 26 patients with TAD did not demonstrate any association of the disease or the immune response potential with any specific HLA determinant. It is proposed that unlike the general lack of regulation that we have previously observed in patients with systemic lupus erythematosus, the abnormal autoimmune reaction in TAD and probably in other organ-specific autoimmune diseases, is towards a specific organ without affecting other arms and functions of the immune system.

Autoimmune Diseases↗

PubMed2005

Outcome of pediatric hematopoietic stem cell transplantations from Thai unrelated donors matched with high-resolution HLA typing.

The authors evaluated the outcome of ten children given hematopoietic stem cell transplantations from Thai unrelated donors (URD-HSCT) selected using DNA high-resolution typing of both HLA class I and II loci. Six patient/donor pairs (60%) were fully matched; four (40%) were 5/6 matched. Patients had either non-malignant (n=9) or malignant (n=1) diseases. In most cases, graft-versus-host disease (GVHD) prophylaxis composed of cyclosporine and short-term methotrexate. The probability of hematopoietic recovery at day 30 was 90%. The cumulative probability of acute GVHD and of chronic GVHD equaled 44.4 and 0%, respectively. Three patients died of transplant-related complications. The probability of transplant-related mortality (TRM) at 30, 100, and 180 days were 10, 30, and 30%, respectively. The overall and disease-free survival rates were 70 and 70%, respectively. URD-HSCT with donor selection based on high-resolution HLA typing is associated with a low incidence of both severe acute GVHD and graft failure. The observed outcome is comparable to that of children transplanted from HLA-identical siblings.

Adolescent↗

PubMed1981

Takayasu's disease in two brothers. Analysis of HLA types.

Recent studies indicate that certain haplotypes of HLA are frequently associated with Takayasu's disease, and that HLA-A and B loci could determine the predisposition to this disease, especially in women. Ths paper describes two male sibs with Takayasu's disease in whom HLA typing was carried out. In addition, HLA types were determined on A, B, C, and DR loci of all family members. It was found that no haplotypes were shared by the two patients, but that HLA-Bw52, which has been reported to be frequently associated with Takayasu's disease, was found in one of them. The results suggest that the pathogenesis may be multifactorial and not solely linked to HLA.

Adolescent↗

PubMed1991

[Postmortem serologic and biochemical HLA typing with cultivated retinal pigment epithelium cells].

A quick and reliable method for HLA typing of human cadavers has been established. Retinal pigment epithelial cells (RPE) were obtained from cadaver bulbi 8-36 h post mortem (n = 24). After 24 hours, cell growth correlated inversely with the time lapse between the donor's death and bulbus explantation. Cultivated human RPE were stimulated by different Y-interferon (IFN) concentrations and examined by FACS analysis for the expression of MHC class I and II molecules. A concentration of 100 units/ml human Y-IFN was sufficient to induce maximal class I antigen expression by about 90% of cells after 3 days. At 50 units/ml Y-IFN, the cells showed maximal class II antigen expression for HLA-DR, whereas 100 units/ml I-IFN was required for maximal HLA-DQ expression. Higher concentrations of Y-IFN induced a further HLA-DP expression. However, serological HLA typing was performed after cell stimulation with 250 units/ml Y-IFN for 3 days. A concentration of 500 units/ml Y-IFN yielded equivalent results, but 750 units/ml Y-IFN led to poor identification of class I MHC specificities. Unclear serological results on class I specificities were clarified by 1D-isoelectric focusing (1D-IEF), thus allowing full HLA typing of all donor bulbi examined. In summary, successful HLA typing of cultivated RPE is dependent on both the Y-IFN concentration and the time lapse between stimulation and typing of the RPE. The method provides a much improved basis for cadaver cornea grafting.

Adolescent↗

PubMedDate not supplied

[The utility of class I HLA antibodies screening in a Tunisian obstetric department in order to select good HLA typing reagents].

In order to reduce the cost of the serologic class I HLA typing, we have established a screening program for HLA antibodies among obstetric patients. Class I HLA antibodies were identified by standard microlymphocytotoxicity test using a panel of 100 lymphocytes. In the study period, carried out between January 2000 and June 2002, 817 women were tested, most of them (62%) during the last trimester of pregnancy and in the other cases after delivery. These patients, aged between 18 and 45 years, were in the majority (88%) multiparous. From the total number of 817 maternal serum samples screened, 194 specimens (23,74%) tested positive for HLA antibodies. Thirty eight HLA specificities were characterised in 110 maternal sera of which 62 contained monospecific HLA antibodies. HLA-A2 and HLA-B51(5) were the most common specificities characterised in this study. HLA alloimmunization was present since the first pregnancy. There was no statistically significant linear correlation between HLA alloimmunization and the number of pregnancies. Fifty maternal serum samples (6,11%) could be used as HLA typing reagents. Of these 50 sera, 36 had monospecific HLA antibodies. These useful antisera covered a total of 30 specificities: 8 HLA-A and 22 HLA-B. The cost of self - screening for useful antisera as estimated at dollars 62/mL, the personnel was not considered. However, the lowest cost of commercial HLA typing sera is approximately dollars 400/mL. Our study showed the utility and the net economic advantage to use maternal sera as reagents in our new HLA laboratory with limited budget.

Adolescent↗

PubMed1996

DNA-based HLA typing for cord blood stem cell transplantation.

Molecular analysis of the HLA loci has revealed a pattern of extensive sequence polymorphism. For the class II loci, the polymorphism is localized to the second exon, whereas for the class I loci, both the second and third exons are polymorphic. These polymorphic regions encode the peptide binding groove and appear to be functionally significant in terms of disease susceptibility and transplantation. However, much of this polymorphism cannot be detected by serologic HLA typing methods. DNA typing methods based on PCR amplification and hybridization with sequence-specific oligonucleotide (SSO) probes can distinguish the many allelic sequence variants identified at these loci. The use of arrays of immobilized SSO probes allows genetic typing at many polymorphic sequence motifs in a single PCR and single hybridization reaction, making possible the development of simple, robust, and automated tests. PCR-SSO probe typing of the HLA loci requires very little sample material, is capable of either general or fine discrimination of alleles, and can be used to detect maternal contamination of cord blood. The application of this approach to typing HLA class I and II loci is discussed with regard to hematopoietic transplantation therapy.

Female↗

PubMed1981

Technical and theoretical considerations in the HLA typing of amniotic fluid cells for prenatal diagnosis and paternity testing.

HLA typing of amniotic fluid cells has been used for the prenatal diagnosis of the HLA linked diseases congenital adrenal hyperplasia (21-OH-deficiency (21-OH-def) type) and complement C4 deficiency and it has also been used for the prenatal determination of paternity. There are, however, technical difficulties in this test associated with the weak expression of some B locus antigens on amniotic fluid cells, and theoretical difficulties related to associations between particular HLA antigens and the 21-OH-def allele. Since certain HLA-B locus antigens are found in significantly increased frequencies among patients with 21-OH-def, there is a relatively high incidence of HLA-B homozygosity among the patients and over 40 per cent of the parents of these patients share one or more HLA-B locus antigens. Results of some prenatal HLA typing tests may thus be difficult to interpret, and supplementary tests should be used whenever possible. HLA typing of amniotic cells is, however, the only available procedure for prenatal diagnosis of C4 deficiency and it is the best available procedure for prenatal determination of paternity. A modification of our original procedure allows HLA typing to be performed with increased numbers of HLA typing sera, and sera with optimum reactivity for amniotic fluid cells have now been selected for the definition of most of the more commonly expressed HLA antigens. Although amniotic fluid cells do not express DR Antigens, amniotic fluid cells can be typed for the HLA-linked marker glyoxalase I (GLO) and this may be the informative for prenatal diagnosis in some cases.

Adrenal Hyperplasia, Congenital↗

PubMed1997

Acquisition and use of DNA-based HLA typing data in bone marrow registries.

The increased use of DNA-based typing techniques has improved the accuracy and reliability of HLA types assigned to patients requiring an allogeneic bone marrow transplant and their potential donors, facilitating better donor selection. The benefits of this technology, which will completely replace serologic typing within the next few years, have not yet been fully exploited since the typing information obtained in the form of DNA sequence polymorphisms is presently converted to an HLA allelic type for submission to a registry. Furthermore, within the registry, the allelic type may be further converted to a serologic antigen for use in the search and match process. Because the current nomenclature system makes selection of donors who are likely to provide optimal matches difficult, it is critical that DNA-based HLA typing data be recorded by registries as sequence polymorphisms tested as positive or negative rather than interpreted HLA types and that searching and matching utilize these polymorphisms. Until this transition is complete, we will not fully utilize this powerful HLA typing technology to best serve those patients seeking unrelated donors.

Alleles↗

PubMed1994

Strategies for prenatal HLA typing for potential cord blood donor evaluation.

The reasons for prenatal HLA typing for potential cord blood stem cell donor evaluation are reviewed and the strategies for doing so are summarized. Cultured fetal cells are class I HLA typed by modified serological techniques. When indicated, the fetal cells are also class II HLA typed by one or another DNA typing method. The same procedures can be used for the prenatal identification of a potential donor for an affected fetus.

Blood Donors↗