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PubMed1992

Retinal pigment epithelial cells in post mortem HLA typing of corneal donors.

Corneas used for transplantation are typically obtained from donors up to 48 hr post mortem. By this time, standard HLA typing usually is impossible because of the lack of viable lymphocytes in spleen and peripheral blood. To increase the number of HLA-typed corneas, we developed a method in which the retinal pigment epithelial (RPE) cells of the donor eye are isolated, cultured in the presence of 1000 IU/ml interferon-gamma (IFN-gamma), and, after 4 d, are typed for HLA Class I and Class II antigens in the standard NIH cytotoxicity assay. Sixty five donors were typed simultaneously using peripheral blood lymphocytes and RPE. One hundred and sixteen out of 120 HLA-A antigens, 125/127 HLA-B, 106/108 HLA-C, and 92/100 HLA-DR antigens were identical using the same technique. Donor age, sex, cause of death, time of enucleation post mortem, and time of RPE preparation post mortem, as well as duration of culture period prior to stimulation with IFN-gamma did not correlate with the results of HLA typing. These data show that RPE cells can substitute for lymphocytes in post mortem HLA typing. Consequently, every donor with corneas suitable for transplantation can be prepared for matched transplantation.

Adolescent↗
PubMed1989

HLA types in patients with rheumatoid arthritis developing leucopenia after both gold and sulphasalazine treatment.

HLA types, especially HLA-DR3, are associated with the development of toxic reactions in patients with rheumatoid arthritis after treatment with gold or D-penicillamine. In this study, after treatment with sulphasalazine, leucopenia was observed in three patients, who all had a history of leucopenia after previous gold treatment. The HLA types of these patients did not include HLA-DR3; the two patients developing mild leucopenia had HLA-DR2 and the one developing agranulocytosis had HLA-DR4.

Adult↗
PubMed1992

Correlation of HLA types and clinical findings in Japanese patients with hyperthyroid Graves' disease: evidence indicating the existence of four subpopulations.

OBJECTIVES: To re-evaluate the associations of HLA types with Japanese patients having hyperthyroid Graves' disease, HLA types and clinical findings were correlated. DESIGN: Four independent clinical findings (ophthalmopathy, family history, age at onset and size of goitre) and two autoantibody titres, thyrotrophin binding inhibitor immunoglobulin (TBII) and anti-thyroid microsmall antibody (anti-M), were analysed. PATIENTS: Eighty-eight Japanese patients with hyperthyroid Graves' disease and 186 control subjects were assessed. MEASUREMENT: Serological HLA typing was performed on 73 antigens in HLA-A, -B, -C, -DR and -DQ loci. HLA-D and -DP (29 antigens) were determined by the restricted fragment length polymorphism (RFLP) methods. TBII and anti-M were measured by commercially available kits. RESULTS: Patients with potent antibody titres had HLA antigens commonly seen among all the patients with Graves' disease. Interestingly, however, HLA-B35 and -Cw11 were found to relate with negative and/or weak TBII, and HLA-B7 and absence of HLA-Aw19 with negative anti-M. Significant associations were observed between HLA-DRw8 and large goitre and absence of ophthalmopathy, and between HLA-DQw4 and a negative family history of diffuse goitre (corrected P less than 0.05). Several other antigens were also found to be significant. Among these antigens, four pairs of MHC classes I and II were found to relate to the clinical findings independently. HLA-DQw4 and negative -A31 pair was closely related to ophthalmopathy, negative family history and late onset of disease. The HLA-B5 and -Dw12 pair was associated with ophthalmopathy, positive family history and early onset of disease. The HLA-A11 and negative -DPw2 pair was associated with ophthalmopathy, negative family history and early onset of disease. The HLA-Bw46 and -DRw8 pair did not increase in frequency above that seen with HLA-DRw8 alone. These four antigen groups (HLA-DRw8, HLA-DQw4 and negative-A31, HLA-B5 and -Dw12, and HLA-A11 and negative -DPw2) were observed in the majority (68%) of patients with Graves' disease and at a significantly higher incidence than in the control group (P less than 0.05). CONCLUSION: There are four subpopulations of Japanese patients with hyperthyroid Graves' disease. This is one of the reasons why the association of HLA types in Japanese patients is rather weak when they are studied as one group.

Adolescent↗
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↗
PubMed2000

[Quality control for HLA typing].

In November 1999 we started the quality control exercise for Polish institutions involved in HLA typing. Five out of eleven invited institutions responded favourably and took part in the first run of the workshop. In the second trial, presently reported, number of labs increased to eight. Each centre received 4 blood samples for serological typing of HLA class I and 5 samples for DNA HLA class II typing. As in the previous workshop, HLA class II typing should be performed at least for DRB1 alleles at the low resolution level. The paper presents the results of the second run of standardisation.

HLA-DQ Antigens↗
PubMedDate not supplied

Serologic HLA typing in infantile spasms.

Serologic HLA typing was performed on 29 patients with infantile spasms and hypsarrhythmic patterns in their electroencephalograms (EEGs). There were no significant increases in the frequencies of HLA-A, B, and C antigens in the infantile spasm group as compared with controls. However, there was a significant increase in the frequency of DRw52 in the infantile spasm patients (90%) as compared with controls (72%) (p less than 0.05). In addition, 3 of 12 white infantile spasm patients demonstrated the complete B18,DR3 (DRw52) haplotype; none of 150 control white subjects showed this haplotype. These findings contribute to evidence that immunological mechanisms may be involved in the pathophysiology of infantile spasms.

HLA Antigens↗
PubMed2002

Is prenatal HLA typing of uncultured amniocytes before the collection of related allogenic cord blood helpful?

The collection of related allogenic cord blood is gaining increasing importance in families with one child affected by haematopoietic disease. Within a family, there is only a 25% chance of a full HLA match between siblings. 50% of all collected cord blood samples cannot be used because of poor quality. Because of this, the determination of HLA type is useful for planning the collection of related allogenic cord blood transplants. We studied whether HLA typing is possible during late pregnancy if amniocentesis has not been performed during the first trimester. HLA -A, -B and -DRB loci were detected in amniotic fluid, as well as in corresponding cord blood and maternal blood using PCR-SSP. For the first time, HLA typing was performed from uncultured amniocytes. Unambiguous results were obtained from all samples. Fetal HLA-genotype in amniotic fluid was confirmed by typing results from corresponding cord blood. HLA typing of uncultured amniocytes during late pregnancy is a reliable and fast method. For the first time, prenatal HLA typing by amniocentesis after week 38 of gestation is possible in less than 8 h and without fetal risk.

Adult↗
PubMed1988

Histocompatibility lymphocytic antigen (HLA) typing in patients with acute exacerbation of Hashimoto's thyroiditis.

Histocompatibility lymphocytic antigen (HLA) typing was performed in 6 patients with acute exacerbation of Hashimoto's thyroiditis whose diagnoses were established on the basis of typical histological findings, and was compared with those of 12 with subacute thyroiditis, 33 with general Hashimoto's thyroiditis and also with a control group. There was a high incidence of BW35 in patients with subacute thyroiditis, although it was only seen in 1 of 6 patients with acute exacerbation. The difference was statistically significant (p less than 0.01). Four of 6 patients with acute exacerbation had DR2 and none of them had DR4, which was the reverse of the findings for Hashimoto's thyroiditis patients in general, and the difference in the incidence of DR2 was significant (p less than 0.001). None of the HLA types in patients with acute exacerbation was significantly different from those of the control group. In conclusion, HLA typing in patients with acute exacerbation was different from those of subacute thyroiditis and general Hashimoto's thyroiditis. Acute exacerbation was considered to involve quite a limited and rather unique population among patients with Hashimoto's thyroiditis.

Disease Susceptibility↗
PubMed1996

Interleukin-2 activated lymphocytes show improved sensitivity for class 1 HLA typing.

The use of phytohemagglutinin (PHA)/interleukin-2 (IL-2) activated lymphocytes for HLA typing and the comparison with those of fresh peripheral blood lymphocytes are described. For detecting class 1 HLA antigens, PHA/IL-2 activated lymphocytes showed higher sensitivity than fresh lymphocytes of the peripheral blood in serological microcytotoxicity testing method. Their reaction specificity for the panel of alloantisera for class 1 HLA antigens was the same. On the contrary, for detecting class 2 HLA antigens, PHA/IL-2 activated lymphocytes showed lower sensitivity than those with fresh B-cells. For class 2 HLA typing, the typing with DNA methods showed the best results. Thus, we conclude that a combination of a serological typing method using PHA/IL-2 activated lymphocytes for class 1 HLA antigens with a DNA method for typing class 2 HLA antigens currently offers the best approach for the detection of HLA antigens.

Adult↗
PubMed1994

HLA-type of cerebral vasospasm patients after aneurysmal subarachnoid hemorrhage.

We studied human lymphocyte antigen (HLA) types in a group of 45 patients who had aneurysmal subarachnoid hemorrhage (SAH). A significantly increased frequency of HLA antigen A31 and a significantly decreased frequency of HLA antigen B40 were found. In patients with delayed ischemic neurological deficit (DIND) following aneurysmal SAH and HLA typing, HLA-Bw60 antigen showed significant increases; in patients who did not develop HLA-Aw33 and -Cw4 antigens showed significant. Among the patients with Fisher's Group 3 on CT, in particular, these antigens significantly increased when compared with controls from the same geographic area. These results suggest that HLA-Bw60 antigen plays a role as predisposing factor of DIND resulting from vasospasm following aneurysmal SAH, and that HLA-Aw33 and -Cw4 exert protective influence against DIND.

Adult↗
PubMed1993

Bone marrow transplantation for acute myeloblastic leukaemia: an EBMT Leukaemia Working Party prospective analysis from HLA-typing.

The optimal post-remission therapy for patients with acute myeloblastic leukaemia remains controversial. Allogeneic bone marrow transplantation, autologous bone marrow transplantation, and consolidation chemotherapy are the major options. In order to evaluate their respective value the European Group for Bone Marrow Transplantation conducted a prospective registration study. Patients with newly diagnosed acute myeloblastic leukaemia were registered at the time of HLA-typing and intention to treat in case of presence or absence of an HLA-identical donor was recorded. 27/79 (34%) patients HLA-typed at diagnosis had an identical donor identified. The estimated survivals at 3 years from HLA-typing were 44% and 21% among patients with or without HLA-identical donor, respectively (P = 0.02). 22/26 (85%) patients for whom allogeneic bone marrow transplantation was intended were transplanted but only 15/47 (32%) patients for whom autologous bone marrow transplantation was intended were indeed transplanted (P < 0.001). The survival was 50%, 29% and 17% (P = 0.004) for patients treated with allogeneic bone marrow transplantation, autologous bone marrow transplantation, or chemotherapy, respectively. 40/68 patients HLA-typed in first complete remission had an HLA-identical donor. The estimated 3-year survival among patients typed in first remission with and without HLA-identical donors was 42% and 35% (n.s.), respectively. This technique of early patient registration illustrates the problems of patient selection during the course of the disease and might be used as a complement to randomized trials when comparing bone marrow transplantation and other treatment options.

Adolescent↗
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↗
PubMed1996

[Comparison of kidney transplantation with and without regard to HLA typing].

OBJECTIVE: To compare the functional results after transplantation of locally obtained and assigned kidneys (without taking into account HLA typing) with those after transplantation of kidneys obtained via Eurotransplant (with HLA typing as principal criterion for assignment). PATIENTS AND METHODS: Between December 1983 and December 1993 a total of 236 kidneys were transplanted into 234 patients, 40 kidneys having been obtained via Eurotransplant and 196 removed locally and transplanted directly into patients on the local waiting list according to strict criteria: same blood group; waiting time since decision on transplantation; negative current crossmatch between recipient's serum and donor lymphocytes. Transplantation results were analysed retrospectively according to: ischaemia time, HLA mismatch, postoperative renal failure, postoperative renal function, rejection rate and transplant survival. Mean observation period was 55 months for the local and 50 months for the Eurotransplant kidneys. RESULTS: The number of HLA matches was higher in Eurotransplant group (P < 0.001). However, the cold ischaemia time was greater for this group (20.2 vs 15.7 hours; P < 0.01). Acute renal failure was less common with locally assigned kidneys (33 vs 53%: P < 0.02). There were no significant differences with regard to one-year and five-year renal function (serum creatinine; percentage of normal): 90.2% local vs 88.3% Eurotransplant and 81.8% vs 62.3%, respectively). Survival rates were also similar (96.9% local vs 95% Eurotransplant after one year, 94.4% vs 90% after 5 years). CONCLUSION: Local assignment by waiting time and blood group gave results that were similar to those via Eurotransplant based on HLA typing criteria.

Adolescent↗
PubMed1990

Dermatitis herpetiformis in two American blacks: HLA type and clinical characteristics.

Dermatitis herpetiformis is a rare blistering skin disease characterized in part by granular IgA deposits at the dermoepidermal junction, an associated gluten-sensitive enteropathy, and a strong association with the human histocompatibility leukocyte antigen (HLA)-A1 (74% of patients with dermatitis herpetiformis), -B8 (88%), -DR3 (95%), and -DQw2 (100%). Dermatitis herpetiformis is rarely seen in American blacks and some investigators have postulated that this finding may be due to the decreased frequency of HLA-A1 and -B8 in American blacks compared with Caucasians (American blacks: HLA-A1 = 15.3%, HLA-B8 = 10.7%; Caucasian: HLA-A1 = 26.4%, HLA-B8 = 18.3%). This report describes two American blacks with dermatitis herpetiformis and reports the results of HLA typing of these subjects for HLA-A, -B, -C, -DR, and -DQ antigens. HLA typing revealed that neither patient expressed HLA-A1 or -B8; however, both patients did express the class II antigens most frequently seen in dermatitis herpetiformis, HLA-DR3 and -DQw2. Comparison of HLA class II antigen frequency in normal American blacks and Caucasians reveals a similar frequency of HLA-DR3 and -DQw2 (American blacks: HLA-DR3 = 27.6%, HLA-DQw2 = 40.9%; Caucasian: HLA-DR3 = 22.6%, HLA-DQw2 = 32.9%). These data confirm the importance of the HLA class II region in the pathogenesis of dermatitis herpetiformis. In addition, these data suggest that the rare occurrence of dermatitis herpetiformis in American blacks is not due to the decreased frequency of the HLA class I antigens -A1 and/or -B8 but rather is related to differences in the HLA class II region not detected by routine HLA typing.

Biopsy↗
PubMed2001

Influence of HLA-A, HLA-B, and HLA-DR matching on rejection of random corneal grafts using corneal tissue for retrospective DNA HLA typing.

AIM: To establish if coincidental HLA-A, HLA-B, and HLA-DR tissue matching is associated with a reduced likelihood of corneal graft rejection. METHODS: Organ culture preserved random donor corneas were used for penetrating keratoplasty (PKP). Corneal tissue from all graft recipients and donors or blood samples from recipients after repeated transplantation were obtained in order to perform retrospective molecular HLA typing. A group of 21 recipients with a rejection episode (cases) after corneal transplantation was compared with a control group of non-rejectors (n = 43). 31 graft recipients were considered as high risk patients. The influence of HLA-A, HLA-B, and HLA-DR matching on rejection free graft survival time was analysed with Kaplan-Meyer statistics and Cox regression. RESULTS: A prolonged rejection free survival time was observed in graft recipients with one or two HLA-A matches (log rank test, p = 0.034). This effect was also observed in high risk graft recipients with one or two HLA-DR matches (log rank test, p = 0.030). CONCLUSIONS: Coincidental HLA-A and HLA-DR matches were observed and associated with a prolonged rejection free survival time in the total group and in the high risk group, respectively. These results support the beneficial effect of prospective HLA-A and HLA-DR typing upon corneal graft survival.

Adolescent↗
PubMed1996

Effect of HLA type and hypocomplementaemia on the expression of parvovirus arthritis: one year follow up of an outbreak.

OBJECTIVES: To determine the effect of HLA type and hypocomplementaemia on the duration and severity of joint involvement in parvovirus infection (HPV). METHODS: Forty seven patients were selected on a geographical basis from 83 with proven HPV infection during an outbreak that occurred in Oxfordshire in 1993. They were contacted by questionnaire a year later. Thirty five patients were available for examination and blood sampling. Subjects were typed for HLA-DRB1 alleles and HLA-B27 status. Immunological profiles, including C3 and C4 complement components, were determined. RESULTS: Joint symptoms occurred in all patients. They resolved within a week in 12 patients and persisted beyond one year in 19. On review, none had a picture of rheumatoid arthritis, but three patients had developed carpal tunnel syndrome. Decreased C4 was found in four. The HLA frequencies were similar to those in controls; however, joint symptoms persisted for more than one week in all HLA-DR4 positive patients (p = 0.009). There was no relation between the severity of joint symptoms and either HLA type, or hypocomplementaemia. CONCLUSIONS: Joint symptoms are common in parvovirus infection and the presence of HLA-DR4 may be associated with persistence of joint symptoms beyond one week. This study revealed no evidence of progression to rheumatoid arthritis.

Adult↗
PubMed1994

DNA-based HLA typing of nonhematopoietic tissue used to select the marrow transplant donor for successful treatment of transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TAGVHD) is a rare and usually fatal complication of blood transfusion which can arise when immunocompetent lymphocytes from the donor of a cellular blood product are transfused into a severely immunocompromised recipient. We describe the case of an 8-month-old male with a severe combined immunodeficiency syndrome who developed TAGVHD after receiving an unirradiated transfusion. Serologic HLA typing of the parents, the patient, and the blood donor demonstrated the foreign origin of circulating lymphocytes, confirming the diagnosis of TAGVHD. The manifestations of TAGVHD did not respond to medical immunosuppressive therapy, and bone marrow transplantation was planned to treat the underlying immunodeficiency as well as the TAGVHD. By using DNA-based class I and class II HLA typing, the child's HLA type was determined from nonhematopoietic tissues. This information proved critical in selecting the bone marrow donor. The child received immunosuppression, myeloablation, and a T-depleted, maternal bone marrow graft mismatched at one HLA class II allele. Trilineage hematopoietic engraftment occurred within 3 weeks, and the child remains clinically stable with no evidence of TAGVHD more than 2 years after the transplant. This case illustrates that TAGVHD can be successfully treated by allogeneic bone marrow transplantation and that DNA-based HLA typing can play a unique role in the diagnosis and management of TAGVHD.

Bone Marrow Transplantation↗