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At least 19 recordsLinked to original sources
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↗
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↗
PubMed1979

Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) by HLA typing.

Congenital adrenal hyperplasia (C.A.H.) due to 21-hydroxylase deficiency is an HLA-linked recessive disorder. HLA-A and B antigens are expressed on amniotic cells. Prenatal diagnosis of C.A.H. by HLA typing of families and amniotic cells was attempted in two at-risk families. In one family HLA typing indicated that the fetus would have C.A.H., and this prediction was confirmed after birth. In the second family, HLA typing indicated that the fetus would be an unaffected, phenotypically normal carrier of the disease gene, and this prediction was also confirmed after birth.

Adrenocortical Hyperfunction↗
PubMed1979

Early detection of idiopathic haemochromatosis: relative value of serum-ferritin and HLA typing.

A study of 18 unrelated families with idiopathic haemochromatosis (I.H.C.) was undertaken to define the relative values of HLA typing and serum-ferritin estimation in the early detection of the disease. Sharing of both HLA haplotypes with the proband indicated a high risk of I.H.C. in siblings; but HLA typing was of limited value in detecting affected offspring. Non-identical HLA indicated a low risk of I.H.C. in both siblings and offspring. The presence of HLA A3 was not clinically useful as a marker for I.H.C., since this antigen was also present in 40% of unaffected relatives. In contrast, the serum-ferritin concentration was elevated in 96% of patients with I.H.C. and in only 5% of unaffected relatives. HLA typing provides some indication of the risk of I.H.C. in first-degree relatives, but the combination of serum-ferritin, serum-iron, and transferrin saturation remains the most reliable screening regimen for early diagnosis of I.H.C.

Adolescent↗
PubMed1977

Family studies and HLA typing in ankylosing spondylitis and sacroiliitis.

The families of 21 ankylosing spondylitis (AS) and 16 sacroiliitis (SI) patients were investigated and typed for HLA markers. The association of HLA B27 with AS was confirmed, but no strong evidence for the same or other HLA markers being associated with SI was found. Inheritance patterns in families were analyzed according to the multifactorial and monofactorial models. It is proposed that a major gene associated or interacting with the B27 product controls the susceptibility to AS, and that this gene behaves as a dominant with incomplete penetrance. The problem as to whether linkage disequilibrium maintained by selective pressure, or functional epistasis between the "disease gene" and the B27 antigen may be the acting mechanism of association, remains to be elucidated.

Arthritis↗
PubMed2025

Learning predictive signatures of HLA type from T-cell repertoires.

T cells recognize a wide range of pathogens using surface receptors that interact directly with peptides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.TCRs, associated with a specific HLA allele, exhibit sequence similarities that suggest prior antigen exposure. Immune repertoire sequencing has produced large numbers of datasets, however the HLA type of the corresponding donors is rarely available. Using our TCR-HLA associations, we trained a computational model to predict the HLA type of individuals from their TCR repertoire alone. We propose an iterative procedure to refine this model by using data from large cohorts of untyped individuals, by recursively typing them using the model itself. The resulting model shows good predictive performance, even for relatively rare HLA alleles.

Humans↗
PubMed1979

HLA types and immunity in multiple sclerosis.

HLA types and levels of humoral and cell-mediated immune responses to several antigens were studied in a large group of patients with multiple sclerosis, and in controls. Patients were more likely than controls to have the DRw2 antigen. They had higher mean antibody titers to measles but not to cytomegalovirus, herpes 1, or herpes 2, and had less competent cell-mediated responses. Antibody titers to measles were lower and cell-mediated immune responses were more effective in patients with the DRw2 antigen in patients than in patients without it. This apparent specificity for measles suggests that the etiology of multiple sclerosis is related to the immune response to measles or related viruses.

Antibodies, Viral↗
PubMed1978

Recovery of lymphocytes from clotted blood for HLA typing.

A method to recover lymphoid cells from clotted blood for the microcytotoxicity test used in HLA typing is described. The procedure consists of disruption of the clotted blood followed by Ficoll-Hypaque gradient purification of the mononuclear cells. The results of HLA typing of lymphocytes from unclotted and clotted blood were identical.

Blood Coagulation↗
PubMed2025

Evaluating the Antigen and Eplet Accuracy of DQA1 Imputations With the HaploSFHI Two-Field HLA Typing Inference Tool.

Donor/recipient mismatched HLA antigens can lead to the production of Donor-Specific Antibodies by the recipient, which are deleterious to organ transplants. The HLA-DQ locus is the most frequent target, with both the DQ beta and alpha chains involved. For deceased donors in particular, while HLA-DQB1 has been typed in emergencies for a long time, HLA-DQA1 has only recently been included. No imputation algorithmic tool was available to impute HLA-DQA1 until the development of HaploSFHI, trained on 61,393 two-field typings by NGS methods. We evaluated the accuracy of two-field HLA-DQA1 imputation from serological and two-field level HLA-A, B, DRB1, and DQB1 typings. We report a highly accurate two-field HLA-DQA1 prediction using a French test cohort of 7696 individuals, respectively reaching 92.30% and 96.45% accuracy. The average 'False Positive eplet load' stood at 0.19 and 0.07, respectively, and the average 'False Negative eplet load' at 0.18 and 0.08, respectively. A similar performance was obtained on three independent test cohorts of European ancestry (from the USA, the UK, and Portugal). Interestingly, performance was only slightly inferior on five independent test cohorts of other ethnicities (from Hong Kong and the USA) whereas it was significantly lower for two-field DRB1 imputation from its serological level. These results suggest that DQA1 can reliably be imputed even when information is totally missing, with low error risk at both antigen and eplet levels, even if the reference population is not matched. Similar additional initiatives would be welcome to confirm these findings.

Humans↗
PubMed1979

HLA types in corneal diseases.

Evaluation of the results of HLA typing of 187 patients grouped into herpetic keratitis (37), non-herpetic keratitis (43), keratoconus (42), endothelial dystrophy (23), stromal dystrophy (13), lues (5), and injuries (24), failed to show convincing deviations in any of the groups from a normal control series (2900 persons). Yet, as for the herpes group, a rise in B5 must strongly be suspected. The data are presented and possible implications are discussed.

Corneal Diseases↗
PubMed1978

HLA-typing in juvenile diabetics with and without positive family history and in families with one and two diabetic siblings.

HLA-typing was performed in two groups of juvenile-onset diabetics, one with (n = 58) and one without (n = 109) a family history of the disease. The association of this type of diabetes with certain HLA antigens (excess of B8 and B15, shortage of B7) was confirmed. No heterogeneities could be established between the two groups. This suggests that the aetiologic basis in single and familial cases of juvenile diabetes is the same. The hypothesis, that the B8 associated gene is more penetrant than the B15 associated gene, cannot be confirmed. Haplotypes were determined in families with one and two diabetic siblings. The findings of high haplotype concordance among diabetic siblings was confirmed: concordance of 2, 1 and 0 haplotypes in 7, 5 and 3 pairs respectively. There was a low degree of haplotype concordance between diabetics and nonaffected siblings in the families with two diabetics: 2, 1, and 0 haplotypes in 2, 8 and 6 pairs respectively. This led to the hypothesis of negative selection against these HLA-linked "diabetogenic" genes. This tendency was not, however, observed in families with only one diabetic. The report of a high recombination rate in families with juvenile diabetics could not be confirmed.

Adolescent↗
PubMed1977

Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type.

In a study of 972 patients with diabetes mellitus, humoral pancreatic islet-cell antibodies (I.C.Ab.) were detected in highest prevalence in insulin-treated diabetics with (38 per cent) and without (22 per cent) associated overt organ-specific autoimmune disease (A.I.D.) where consideration was not given to the duration of diabetes. They were also detected in 8 per cent of diabetics treated with oral hypoglycemic agents (O.H.A.), but not in diabetics requiring diet alone and in only 0.5 per cent of 434 control subjects. Six per cent of 522 patients with overt organ-specific A.I.D. but not diagnosed to be diabetic had I.C.Ab.s. I.C.Ab.s were present in the sera of 2 per cent of 157 first-degree relatives of I.C.Ab.-positive subjects. In insulin-treated diabetics and, to a lesser extent, in diabetics not requiring insulin, the prevalence of humoral I.C.Ab. was strongly dependent of the duration of the diabetes, being 60 per cent during the first year from diagnosis in the insulin-treated group and falling to 20 per cent at two to five years and to 5 per cent at 10-20 years. The prevalence of I.C.Ab. in insulin-treated diabetics showed no correlation with the patient's age at the time of testing when the duration of diabetes was taken into account. Diabetics who did not require insulin for treatment but who were I.C.Ab.-positive showed a significant tendency to subsequently require insulin and to have a higher prevalence of other autoantibodies than insulin-independent diabetics who were I.C.Ab.-negative. Persistence of I.C.Ab. for more than five years from diagnosis of diabetes was associated with coexistent overt organ-specific A.I.D. and with HLA-B8, A1, and A1 + B8.

Adult↗
PubMed1977

HLA typing and primary cadaver graft survival.

Analysis of 463 consecutive primary cadaver renal transplants showed no influence of HLA match grade on renal allograft survival. Additional categorization according to HLA match grade and degree of presensitization again showed no correlation between match grade and graft survival. Mismatches and matches of specific antigens, cross-reacting groups of antigens, and effect of matching at both locus A and B were also evaluated. There was no significant effect on graft survival except when mismatches against donor A2 and cross-reacting group A2, A28 occurred. A trend toward better graft survival was suggested in recipients matched for A9 and cross-reacting group A9, Aw 23, Aw 24. Although HLA match grade did not influence ultimate graft survival, HLA typing remains important, especially to avoid mismatch against donor A2 antigen. In addition, subsequent detection of new specificities, particularly in other than the A and B loci, may provide significance in the future.

Cadaver↗
PubMed1977

Reactivity of HLA typing sera against cultured lymphoblastoid cell lines and purified peripheral B and T cells from the same original donors.

Anomalous cytotoxicity reactions are observed in some HLA typing sera when cultured lymphoid cells are used as targets. These extra reactions are also detected when the purified B cells from the original donors of the cell lines are used. This observation strongly indicates that these extra reactions are directed to the B cell alloantigens which are normally expressed on B cells of the original donor.

B-Lymphocytes↗
PubMed1976

Nasopharyngeal carcinoma and Burkitt's lymphoma in a Canadian family. I. HLA typing, EBV antibodies and serum immunoglobulins.

Two nasopharyngeal carcinomas of the lymphoepithelioma type and two Burkitt's lymphomas with the characteristic histopathologic features developed in three siblings and one first-degree cousin in a large French-Canadian family. Epstein-Barr virus antibody titres in the two lymphoepithelioma cases but not in the Burkitt's lymphoma cases were, as expected, greatly elevated. HLA typing of the family members failed to disclose HLA antigens A2 and B Sin-2, which have been associated with lymphoepithelioma in Asia. The occurrence, however, of a plasmacytoma in one other first-degree cousin and low serum IgA values in several siblings and cousins suggests the possibility of a genetically determined predisposing B-cell dysfunction in the development of these tumours.

Adolescent↗
PubMed2025

HLA-Typing of Donor-Origin Cells Enriched From Urine Cell Culture of Kidney Transplanted Recipients.

The incomplete or lack of histocompatibility information constitutes a barrier for the early detection and management of de novo donor-specific antibodies (DSA). To improve the quantity and quality of DNA materials for HLA typing, we developed a non-invasive culture-based method, using DNA extracted from enriched donor-derived kidney stem cells (DKSC) selectively cultured from the urine of kidney transplant receipients (KTR) to allow high-resolution typing by next-generation sequencing. This prospective proof-of-concept study evaluated the feasibility and performance of this approach. DKSC were enriched from the urine of 60 KTRs. DNA extracted from culture-enriched DKSC showed significantly higher concentration and better quality than unbound cells, and with identical short tandem repeat (STR) and 100% concordance compared to that obtained from peripheral blood. Our results suggest that cultured-enriched DKSC are non-invasive and useful for determining HLA and other genes for KTRs where donor information is limited or lacking.

Humans↗