DR Types Research Articles

HLA class II DNA-RFLP typing in 102 individuals from Northern Greece.

The serological identification of HLA class II alleles is often doubtful. Since accurate HLA typing is essential for the matching of donor-recipient pairs in allogeneic transplantation, an effort was made to establish DNA restriction fragment length polymorphism (RFLP) typing and to assess the correlation between the serological and RFLP techniques in the population of Northern Greece. One hundred and two healthy individuals (204 HLA-DR alleles) from Northern Greece were HLA-DR, DQ typed with both the microcytotoxicity and the Taq I RFLP method, using three exon-specific probes. DNA-RFLP typing revealed (1) concordant results with serology in 69.9% (142/204) of the alleles and (2) at least one HLA-DR allele discrepant to serology in 30.4% (62/204) of the alleles. Incorrect serological DR types (weak reactions or inability to distinguish between two alleles with a common epitope) were identified in 54 alleles (26.5%), while 3.9% (8/204) of serological "blank" alleles turned out to be definable alleles by RFPL. Of the individuals tested, 10.8% (11/102) were DR-homozygous by RFLP. This comparison of results obtained by serology and RFLP demonstrated the necessity of the clinical application of DNA typing, especially for organ transplantation where accurate HLA typing has an important influence on graft survival.

Lymphocyte subset abnormalities, autoantibodies and their relationship with HLA DR types in children with Type 1 (insulin-dependent) diabetes and their first degree relatives

Type 1 (insulin-dependent) diabetes mellitus is associated with abnormalities of circulating lymphocyte subsets and autoantibodies. To investigate the prevalence of these in non-diabetic siblings and non-diabetic patients of children with Type 1 diabetes, we analysed T-cell subsets of function and activation in 31 families with an index case of Type 1 diabetes and related these to autoantibodies and HLA DR type. Using two and three colour cytofluorimetry, we studied total and activated (HLA-DR+) CD3+, CD4+, CD8+, lymphocytes and on CD4+ lymphocytes the CD45RA/RO "naive" and "memory" cell phenotypes. Diabetic children (mean duration of disease 3.1 years) had a reduced total lymphocyte count (p < 0.05), their non-diabetic siblings a reduced CD4+ T-helper cell count (p < 0.05), and their parents a reduced percentage and number of CD3+ T cells (p < 0.01 and p < 0.05) compared with age-matched control subjects. Diabetic children, their siblings and parents all had significantly increased levels of activated CD4+ T-helper cells (p < 0.01, p < 0.05 and p < 0.01). In diabetic children and their siblings there was a significant over-expression of the CD45RO "memory" cell marker and significant under-expression of the CD45RA "naive" cell marker, whilst these were normal in the parents. Islet cell antibody positive diabetic children had significantly higher levels of CD45RO-expressing CD4+ lymphocytes than those who were islet cell antibody negative (p < 0.05). Amongst the siblings and parents, possession of HLA-DR4 was associated with lower percentages of CD4+ and higher percentages of CD8+ T cells. These findings extend current knowledge about the role of immunoregulatory CD45RA/RO cells in Type 1 diabetes. In addition, they demonstrate lymphocyte subset abnormalities in unaffected family members, some of which may be influenced by HLA DR alleles.

Major histocompatibility complex-encoded antigen processing gene polymorphism in IDDM.

Susceptibility to insulin-dependent diabetes mellitus (IDDM) is greatly influenced by polymorphisms in the genes of the class II region of the human leukocyte antigen (HLA) complex. The complexity of this genetic association and the lack of a direct proof of involvement of HLA class II genes in human IDDM have continued to support speculation on a possible role of genes encoded in the close vicinity of these loci in IDDM. Because the recently discovered transporter associated with antigen processing (TAP) and large multifunctional protease (LMP) genes are encoded in the HLA class II region and are implicated in the processing of antigenic proteins for presentation by HLA class I molecules, they are additional candidates for a role in IDDM pathogenesis. We have analyzed genomic and coding sequence polymorphisms in the LMP2, TAP1, and TAP2 genes of 77 Danish IDDM patients and 102 control subjects. Although patients and control subjects did not differ in TAP1 and LMP2 alleles, we found a striking absence of the TAP2 allele B (long form) in IDDM patients. An analysis of the TAP2 alleles in individual DR types, however, revealed that this phenomenon is likely to be caused by linkage disequilibrium between the two loci. Thus, polymorphisms in the TAP and LMP genes are unlikely to be associated with IDDM.

Restriction fragment length polymorphism of HLA‐DQ and ‐DR allogenotypes in normal Southern Chinese

We have examined the Taq I restriction fragment length polymorphism (RFLP) of the MHC class II regions of 96 normal Southern Chinese with respect to the HLA-DRB, -DQA, and -DQB genes. The data were compared with the DR and DQ serotyping. RFLP correlates well with the serological typing of the DR types of Chinese. Variants are seen in DR2 and DR12. The variant in DR12 with a 10 kb at the upper band (DR12b) is not found in Caucasoids and is more frequent in Chinese (19.4% of the alleles). With the help of DQA and DQB RFLP the assignment of genotyping of DRB types is facilitated. Some of the linkage disequilibrium patterns among DRB, DQA and DQB are different from Caucasoids. This is particularly obvious in the DR2 and DR5 haplotypes. In the 96 Southern Chinese, the 3 commonest haplotype frequencies are: DR12b, DQ alpha 1b, DQ beta 3b (18.3%); DR9, DQ alpha 3, DQ beta 3a (15.7%); DR4, DQ alpha 3, DQ beta 3a (14.2%). The various DR beta, DQ alpha. DQ beta genes can be accurately defined in Chinese by RFLP. Polymerase chain reactions using sequence-specific primers were performed to confirm the various HLA-DRB and -DQB alleles. The use of RFLP is important in the study of HLA matching and HLA-disease association in Southern Chinese.

Influence of human leukocyte antigen matching on liver allograft survival and rejection: “The dualistic effect”

To date only one published large series of human leukocyte antigen matching and liver allograft survival exists, and considerable confusion has arisen about the advantage or disadvantage of human leukocyte antigen matching. In the present study we have reinvestigated the relationship between human leukocyte antigen mismatch and graft survival in 466 first liver allografts, seeking to clarify the relationship between human leukocyte antigen and both acute rejection and the vanishing bile duct syndrome. In view of current criticism regarding the accuracy of serological tissue typing for human leukocyte antigen-DR, we have used both classic serology and restriction fragment length polymorphism analysis to ensure the accurate assignment of recipient DR types. In addition, we have used polymerase chain reaction amplification and allele-specific and sequence-specific oligonucleotide probes to retest the hypothesis that human leukocyte antigen class II matching may increase susceptibility to the vanishing bile duct syndrome. One-year graft survival was significantly lower in patients with zero or two human leukocyte antigen-A mismatches (52% and 63%, respectively) than in those with one human leukocyte antigen--A mismatch (69%) (p = 0.016 and p = 0.018). A similar effect of B mismatching was observed, with a 1-yr graft survival of 73% for those with one compared with 60% for those with two human leukocyte antigen-B mismatches. In contrast no correlation was found between DR mismatch and graft survival. Human leukocyte antigen class I matching appears to influence graft survival largely through the occurrence of acute rejection and the development of the vanishing bile duct syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of human leukocyte antigen matching on liver allograft survival and rejection: “The dualistic effect”

To date only one published large series of human leukocyte antigen matching and liver allograft survival exists, and considerable confusion has arisen about the advantage or disadvantage of human leukocyte antigen matching. In the present study we have reinvestigated the relationship between human leukocyte antigen mismatch and graft survival in 466 first liver allografts, seeking to clarify the relationship between human leukocyte antigen and both acute rejection and the vanishing bile duct syndrome. In view of current criticism regarding the accuracy of serological tissue typing for human leukocyte antigen-DR, we have used both classic serology and restriction fragment length polymorphism analysis to ensure the accurate assignment of recipient DR types. In addition, we have used polymerase chain reaction amplification and allele-specific and sequence-specific oligonucleotide probes to retest the hypothesis that human leukocyte antigen class II matching may increase susceptibility to the vanishing bile duct syndrome. One-year graft survival was significantly lower in patients with zero or two human leukocyte antigen-A mismatches (52% and 63%, respectively) than in those with one human leukocyte antigen-A mismatch (69%) (p = 0.016 and p = 0.018). A similar effect of B mismatching was observed, with a 1-yr graft survival of 73% for those with one compared with 60% for those with two human leukocyte antigen-B mismatches. In contrast no correlation was found between DR mismatch and graft survival. Human leukocyte antigen class I matching appears to influence graft survival largely through the occurrence of acute rejection and the development of the vanishing bile duct syndrome. In those patients who underwent liver biopsies, 49% (28 of 57) without acute rejection had a single B mismatch compared with 32% (88 of 263) with acute rejection (x2 = 5.5, p < 0.025). In addition, a complete human leukocyte antigen-A mismatch was more common in those who developed the vanishing bile duct syndrome than in those with normal graft function (54% vs. 38%; X2 = 4.26, p < 0.05). In contrast to previous reports from this unit, no relationship between human leukocyte antigen-DR or -DQ mismatch and the vanishing bile duct syndrome could be detected. These findings indicate that human leukocyte antigen class I compatibility exerts a dual effect on the survival of primary liver allografts. Although some human leukocyte antigen-A and –B matching may be desirable for liver transplantation, full class I matching may have an adverse effect. (HEPATOLOGY 1993;17:1008–1015.)

Association of HLA-DR4-Dw15 (DRB1*0405) and DR10 with rheumatoid arthritis in a Spanish population.

To analyze the associations of HLA class II antigens with rheumatoid arthritis (RA) in a Spanish population. We used DNA oligotyping to determine DR types, DQA1 and DQB1 alleles, and DR4 variants in 70 unrelated seropositive RA patients and 189 healthy controls living in Spain. A significantly higher frequency of DR4 was seen in RA patients compared with controls (relative risk [RR] = 2.40). The DR10 specificity correlated most strongly with disease susceptibility (RR = 3.84). A significant decrease in the frequency of DR7 was observed in the RA patients (RR = 0.48). DR4-Dw15 (DRB1*0405) was found to be the unique DR4 allele associated with RA (RR = 4.27, P < 0.05), whereas Dw4 (DRB1*0401) and Dw14 (DRB1*0404/0408) showed no association, and both Dw10 (DRB1*0402) and Dw13 (DRB1*0403/0407) were negative risk factors for the disease. Approximately one-third of the cases of RA could not be explained by the "shared epitope" hypothesis. Investigation of the DQ alleles associated with DR4 showed that the haplotype Dw15-DQ8 (DRB1*0405-DQB1*0302) was a susceptibility factor for RA (RR = 6.36, P < 0.05). Our results suggest that HLA class II alleles involved in RA susceptibility can vary among different Caucasian populations.

Superior renal graft survival in caucasian patients with DR types associated with insulin dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and goodpasture's syndrome (GP): [formula omitted] and PI Terasaki, UCLA Tissue Typing Laboratory, Los Angeles, CA

Superior renal graft survival in caucasian patients with DR types associated with insulin dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), and goodpasture's syndrome (GP): [formula omitted] and PI Terasaki, UCLA Tissue Typing Laboratory, Los Angeles, CA

Analysis of HLA-DR types of unexplained recurrent spontaneous aborters in the Japanese population by oligonucleotide-DNA typing.

To examine whether unexplained recurrent spontaneous abortion (URSA), defined as 2 or more consecutive spontaneous abortions, is correlated with a particular DR type in the Japanese population, we determined the HLA-DR types of 82 primary aborters and 21 secondary aborters by DNA typing utilizing the polymerase chain reaction (PCR) and hybridization with sequence-specific oligonucleotides (SSOs). The DR gene frequencies of the patient group were compared with those of a normal group at three different levels of DR-definition (27, 13 and 11 DR types). At none of the three levels of comparison was any particular DR type with a frequency differing significantly between the patient and normal groups detected in Japanese URSA patients. Furthermore, we examined whether URSA was correlated with the degree of compatibility of HLA-DR antigen within patients and their husbands. Comparison of the DR compatibility between patients and normal couples was made in two different ways, i.e., comparison of the numbers of couples with mismatches and comparison of the average number of mismatches. For either of these two comparisons, we observed no difference in DR compatibility between patients and normal couples. Our results suggest that URSA is not correlated with any particular DR type and that the condition cannot be explained simply by DR compatibility between husband and wife.

Rapid DNA typing utilizing immobilized oligonucleotide probe and a nonradioactive detection system application to HLA-DR typing of the Japanese population

We established a rapid and simple method of HLA-DR genotyping, and applied it for analysis of the Japanese population. Our method includes rapid preparation of DNA samples from buccal mucosa, incorporation of biotin-dATP into DRB genes during amplification by the polymerase chain reaction, hybridization with sequence-specific oligonucleotide (SSO) probes immobilized on nylon membranes via poly (dT) tails, and detection of the hybridization signal as chemiluminescence. We carried out DR typing of 30 Japanese donors using 20 different immobilized SSO probes, and obtained unambiguous typing signals showing perfect correlation with their serologic DR types. The genotyping also enabled us to identify several DR types unique to the Japanese population, such as DRw12b (DRB1 ∗1202), DRw14c (DRB1 ∗1405), and serology blank type, DR‘JX6’ (DRB1 ∗1403). The method presented here would be suitable for routine DR typing in tissue-typing laboratories.

New polymorphic HLA-DR epitopes recognized by three monoclonal antibodies produced against DR103 transfected L cells.

Production of monoclonal antibodies directed against polymorphic epitopes of HLA class II molecules using whole human cells as immunogen has often proved ineffective, because most of the antibodies produced are directed against non-MHC human cell surface molecules. One approach to overcome this problem is the use of transfected mouse L cells expressing a single HLA class II allele as immunogen. By immunizing C3H mice with DR103-transfected L cells, we obtained 3 mAb, OHA TM901, OHA TM902, and OHA TM903, that recognize different polymorphic epitopes of the HLA-DR molecule. The molecular specificities of the 3 mAb were determined on a large panel of B-lymphoblastoid cell lines (B-LCL), peripheral blood cells and HLA class II transfectants from the XIth International Histocompatibility Workshop. Interestingly, the 3 polymorphic mAb detect new HLA-DR epitopes shared by several specificities: OHA TM901 reacts with DR1 (DR101, DR103), DR9 (DR901) and DR10 (DR1001) molecules; OHA TM902 recognizes the same molecules but also DR8 (DR801, 802, 803); OHA TM903 reacts with all DR types except DR3 (DR301, 302), DR7 (DR701, 702) and DR52. Surprisingly, OHA TM901 reacts with DR9 transfectants and B-LCL but not with DR9 peripheral blood lymphocytes. Biochemical analyses indicate that the 3 mAb immunoprecipitate HLA-DR products and react in western blots with DR alpha/beta-dimer but not with free alpha- or beta-chains. This study shows that transfected L cells are very useful tools for the production and the fine characterization of mAb recognizing polymorphic epitopes of HLA class II molecules.

Human T cells cannot act as autonomous antigen-presenting cells, but induce tolerance in antigen-specific and alloreactive responder cells.

The ability of two HLA-DR-expressing human T cell clones to function as antigen-presenting cells (APC) was investigated using highly purified T cells. The results demonstrated that these T cell clones are unable to act as autonomous APC, and that recognition of nominal or alloantigens on the surface of T cells leads to a state of nonresponsiveness. The first observation was that a T cell clone with specificity for the 306-324 peptide of influenza hemagglutinin (HA), and raised from a DR1 responder, exhibited apparent degeneracy of major histocompatibility complex restriction when cultured with peptide in the presence of peripheral blood mononuclear cells (PBMC) expressing a wide variety of structurally unrelated DR types. However, when the PBMC were pulsed with peptide and washed before coculture with the clone, peptide was exclusively recognized with DR1Dw1. This implied that in the presence of soluble peptide the T cells were displaying ligand to each other, and that the third-party APC were providing costimulatory signals. To test the ability of T cells to act as autonomous APC, accessory cell-free preparations of two DR1-restricted clones were cultured with peptide in the presence or the absence of added B cell APC. T cell purity was established by the absence of proliferation in response to the mitogen phytohemagglutinin (PHA). PHA-nonresponsive T cells were completely unable to proliferate in response to peptide alone; furthermore, preculture of the HA-specific clone, in the complete absence of accessory cells, with the same concentration of peptide (1 microgram/ml) that induced optimal proliferation when presented by conventional APC, led to profound nonresponsiveness. The same phenomenon was also observed when two of three anti-DR1 alloreactive T cell clones were precultured with a DR1-expressing T cell clone. The ability of the DR1-expressing clone to induce nonresponsiveness in anti-DR1 clones correlated with recognition of the DR1 alloantigen on the DR1-expressing clone.

Progression of HIV-related disease is associated with HLA DQ and DR alleles defined by restriction fragment length polymorphisms.

A cohort of 139 hemophiliacs was typed for HLA D region genes by means of restriction fragment length polymorphisms (RFLPs) detected by HLA DQ and DR gene probes. Disease progression was studied in the 65 HIV antibody-positive patients, who were infected by contaminated clotting factor before 1985. Strong associations were found between disease progression in HIV-infected patients and allelic DNA fragments revealed by a DQ alpha cDNA probe. A 5.5 kb fragment was reduced in frequency and a 4.6 kb fragment increased in frequency (p less than 0.005) in the faster progressing group, as measured both by development of CDC Category IV clinical symptoms and CD4 number less than 200 x 10(6)/l. These results correlate with DR types deduced from the RFLP patterns revealed by DR beta and DQ alpha gene probes. A decrease in DR4 and an increase in both DR5 and the DR3 subtype found in the A1 B8 DR3 haplotype were associated with disease progression (p less than 0.05).

Linkage between HLA-DRB1 and -DRB3 types in the Japanese population analyzed by oligonucleotide genotyping

We analyzed linkage between HLA-DRB1 and -DRB3 types in 219 Japanese donors by oligonucleotide genotyping. In the Japanese population, DRB1 ∗1201 was linked with DRB3 ∗0101 in all donors analyzed; in contrast, most Caucasian DRB1 ∗1201 is known to be linked with DRB3 ∗02(01/02) ( ∗0201 or ∗0202). However, most DRB1 ∗1202 was linked with DRB3 ∗0301. Thus, the two DRw12-related DRB1 types are linked with DRB3 types distinct from each other. All the three DRw14-related DRB1 types, DRB1 ∗1401, DRB1 ∗1402, and DRB1 ∗1405, were linked with DRB3 ∗02(01/02) in the Japanese population, contrasting with the known linkage between DRB1 ∗1402 and DRB3 ∗0101 in other ethnic populations. The serologically “blank” DR type, DRB1 ∗1403, was linked with DRB3 ∗0101. Other DRB1 types, DRB1 types, DRB1 ∗0301, DRB1 ∗11(01/04) ( ∗1101 or ∗1104), and DRB1 ∗13(01/ 02) ( ∗1301 or ∗1302) in the Japanese population were linked mostly with the same DRB3 types, like those known in other ethnic populations.

Joint Report of the Fourth International Bovine Lymphocyte Antigen (BoLA) Workshop, East Lansing, Michigan, USA, 25 August 1990

Blood samples from 54 animals were exchanged between 15 laboratories in nine countries to improve and expand BoLA class I and class II typing. A total of 27 out of 33 (82%) of previously accepted BoLA-w specificities were represented within the cell panel. Seventeen new serum-defined BoLA specificities were accepted by the workshop participants, thus expanding the number of internationally recognized BoLA specificities to 50. The large number of new specificities detected resulted from the number of serological reagents used (n = 1139) and the genetic diversity of the cell panel. Confidence derived from the high percentage of agreement between the laboratories on antigen detection (97.3%; r = 0.84) permitted the removal of the workshop (w) notation from 23 BoLA-w specificities and their acceptance as full status BoLA-A antigens. Two new non-BoLA antigens were also detected, one completely included within the red blood cell factor S' (BoLy-S'), whereas a second (BoLy-w1) did not show any association with tested red blood cell factors. A comparison between serological, isoelectric focusing (IEF) and DNA typing for BoLA class II polymorphism was conducted with a subset of workshop cells. Correlation between the three methods was significant for three combinations of alleles. Three other serologically defined class II specificities were correlated with DR and/or DQ restriction fragment length polymorphism (RFLP) types, whereas six additional IEF types were correlated with DR and/or DQ RFLP types (r greater than or equal to 0.50). Several new IEF, DRB, DQA and DQB RFLP patterns were identified. In 46 animals that were typed for BoLA-DR and DQ genes by RFLP analysis, 46 different BoLA haplotypes were tentatively defined. These 46 haplotypes were distinguished by 31 serologically-defined BoLA-A alleles (and 2 'blanks'), 15 DRB RFLP types (plus up to 10 new DRB RFLP patterns) and 23 DQA-DQB haplotypes.

Autoimmunity in non-human primates: the role of major histocompatibility complex and T cells, and implications for therapy

Two autoimmune disease models were studied in rhesus monkeys: type II collagen-induced arthritis (CIA) and experimental allergic encephalomyelitis (EAE). Unrelated outbred animals were used in these studies. In both models disease resistant and susceptible individuals could be identified. Susceptibility correlated with in vitro cellular responsiveness to antigen in the CIA model. In both models resistant as well as susceptible individuals developed a humoral response to the inducing antigen. However, there is an indication that IgM antibodies play a crucial role in the induction of CIA. No clear association between major histocompatibility complex (MHC) type and disease incidence was found although a higher frequency of a certain DR type was observed in EAE susceptible monkeys. It is likely that both the antigen binding capacity of the MHC class II molecules and the T-cell repertoire play an important role in determining whether disease will develop or not.

HLA‐DR gene frequencies in the Japanese population obtained by oligonucleotide genotyping

We determined HLA-DRB types of 375 randomly chosen healthy Japanese donors using a set of 29 different sequence-specific oligonucleotide (SSO) probes directed against various DRB alleles. Except for a few cases, these SSOs enabled us to identify 33 different DRB types including those detectable only by SSO genotyping. Gene frequencies were calculated for each of the DRB types identified. The "blank" frequency calculated by our SSO typing was essentially zero, in contrast to the considerably high "blank" frequencies reported at serological HLA-DR or cellular HLA-D workshops. This indicates that almost all of the DRB types in the Japanese population are positively detectable by our SSO typing. By comparing the gene frequencies for each of the DR types obtained by our SSO typing with those obtained by immunological typing at workshops, significant differences were observed for several of the DR types.

HLA Associations with Hashimoto's thyroiditis

There is disagreement over the HLA-DR associations of Hashimoto's (goitrous) thyroiditis. We have studied 86 English Caucasian patients with this condition whose DR types were determined by restriction fragment polymorphism analysis. HLA-DR3 was significantly more frequent in these patients than in 100 controls (chi 2 = 7.09; P less than 0.01). The relative risk was 2.23 and aetiological fraction 0.29. HLA-DPB and DQB alleles were analysed in a proportion of these subjects by enzymatic DNA amplification and oligonucleotide probing. The only significant finding was an excess of HLA-DQw2 (in linkage disequilibrium with DR3) in the Hashimoto group (chi 2 = 7.43, P less than 0.007). These results do not support a difference between goitrous and atrophic thyroiditis based on respective associations with HLA-DR5 and DR3, but confirm a recent study in which HLA-DR3 was associated with Hashimoto's thyroiditis. However, it is possible that genes telomeric to DR3 may be involved in determining which type of thyroiditis a patient with autoimmune hypothyroidism develops.

An analysis of synthetic peptide restriction by HLA-DR alleles in T cells from human subjects, naturally sensitized by Streptococcus mutans.

T cells from most human subjects show significant in vitro proliferative responses to a 185-kDa surface Ag from Streptococcus mutans as well as to synthetic peptides derived from the sequence of a Mr 3800 streptococcal Ag. T cells from subjects expressing each of the alleles from DR1 to DR7 responded to synthetic peptides of 17 or 21 amino acid residues. Furthermore, inhibition studies with mAb to HLA class I and class II Ag showed that the DR Ag was a restriction molecule for the proliferative responses. Mouse L cells transfected with DR1, DR2, DR4, DR5, and DR7 were used to confirm the permissive nature of the responses. An analysis of the fine specificity of the responses showed that the minimum peptides capable of stimulating T cells from subjects with different DR types varied by one or two residues. For DR2 and DR3 the shortest peptide was residues 6-15, an additional serine (residue 5) was required for DR1 and DR7 and an aspartic acid (residue 4) for DR4, DR5, and DR6. Successful oral-mucosal bacterial colonisation in humans, by a largely commensal Streptococcus, might be associated with the permissive nature of the HLA-DR restriction of the response to a major streptococcal cell surface peptide. The peptide recognised in association with the HLA-DR molecule may induce an immune response that prevents central entry of the organism from the peripheral mucosal site.

Genetic differences shown by HLA typing among Japanese patients with euthyroid Graves' ophthalmopathy, Graves' disease and Hashimoto's thyroiditis: genetic characteristics of euthyroid Graves' ophthalmopathy

Euthyroid Graves' ophthalmopathy (EO) is an ophthalmic disorder without persistent hyperthyroidism. To elucidate genetic differences among EO, Graves' disease (Gr) and Hashimoto's thyroiditis (H), we analysed HLA-A, B, C, DR, DQ, D and DP types in 23 Japanese EO patients, 88 Gr patients, 46 H patients and 186 control subjects utilizing assays of lymphocyte cytotoxicity and restriction fragment length polymorphism (RFLP). When compared with the control subjects, EO patients showed significant associations with HLA B40 (w61), DR9, DQw3, and Dw15 (P less than 0.01) and with HLA B12 and Cw1 (P less than 0.05). When allowance was made for the number of antigens tested, only DQw3 was significant. Significant differences were found between EO and Gr (DPw2), and between EO and H (Cw1) even after correction of P values. Comparisons between EO and related subgroups of Gr confirmed the heterogeneity of EO again. It is concluded from these results that EO is associated with different HLA types from Gr and H.