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PubMed2005

Epstein-Barr virus gp42 is posttranslationally modified to produce soluble gp42 that mediates HLA class II immune evasion.

Epstein-Barr virus (EBV) resides as a persistent infection in human leukocyte antigen (HLA) class II+ B lymphocytes and is associated with a number of malignancies. The EBV lytic-phase protein gp42 serves at least two functions: gp42 acts as the coreceptor for viral entry into B cells and hampers T-cell recognition via HLA class II molecules through steric hindrance of T-cell receptor-class II-peptide interactions. Here, we show that gp42 associates with class II molecules at their various stages of maturation, including immature alphabetaIi heterotrimers and mature alphabeta-peptide complexes. When analyzing the biosynthesis and maturation of gp42 in cells stably expressing the viral protein, we found that gp42 occurs in two forms: a full-length type II membrane protein and a truncated soluble form. Soluble gp42 is generated by proteolytic cleavage in the endoplasmic reticulum and is secreted. Soluble gp42 is sufficient to inhibit HLA class II-restricted antigen presentation to T cells. In an almost pure population of Burkitt's lymphoma cells in the EBV lytic cycle, both transmembrane and soluble forms of gp42 are detected. These results imply that soluble gp42 is generated during EBV lytic infection and could contribute to undetected virus production by mediating evasion from T-cell immunity.

Amino Acid Sequence↗
PubMed1994

HLA class II and susceptibility and resistance to insulin-dependent diabetes mellitus in a population from the northwest of Spain.

The role of HLA class II alleles in genetic predisposition to insulin-dependent diabetes mellitus (IDDM) was examined using Polymerase Chain Reaction/oligonucleotide probe typing (PCR/SSOs) of eight HLA class II loci in 58 IDDM patients and 50 healthy controls from the Northwest of Spain (Asturias). We compared the distribution of HLA class II alleles, haplotypes and genotypes between IDDM patients and controls, and tested three recently proposed HLA-IDDM susceptibility theories. By using the aetiologic fraction (delta) as an almost absolute measure of the strongest linkage of disequilibrium of a HLA marker to the putative Type I susceptibility locus, it has been found that the strength of association of the HLA markers may be quantified as follows: DQA1*03-DQB1*0302 or DQA1*0501-DQB1*0201 > DR3 or DR4; presence of more than one dimer DQ alpha beta of the six proposed by Rønningen > non-Asp57 DQ beta and Arg52 DQ alpha > Arg52 DQ alpha > non-Asp57 DQ beta/non-Asp57 DQ beta > DRB1*0301; DQA1*0501-DQB1*0201 > DQA1*03-DQB1*0302; DQB1*0302. The presence of at least one Asp57 DQ beta allele was the best protection HLA marker to IDDM in our population. Therefore, the above data confirm that IDDM susceptibility to HLA locus is linked more to DQ than DR.

Adolescent↗
PubMed1993

[Ectopic expression and the significance of HLA-class II antigens in the myocardium in patients with dilated cardiomyopathy].

Expression of HLA-class II antigens (DQ, DP) in the myocardium of patients with different heart diseases and normal controls was studied with indirect immunofluorescence (IIF). The positive rates in different groups were as follows: dilated cardiomyopathy (DCM, 12/13,+- ), rheumatic heart disease (2/4, +-+ + +), congenital heart diseases (1/14,+), left atrial myxoma (0/1) and normal controls (1/8,+). The immunofluorescent area was in the endocardium and endothelial cells of the blood vessels (VIII factor related antigen positive areas in dual staining of the myocardium). There were significant differences between the positive rates of DCM and those of other heart diseases including rheumatic heart disease, congenital heart diseases and left atrial myxoma (chi 2 cor = 15.3, P < 0.001), as well as between DCM and normal controls (chi 2 cor = 9.9, P < 0.01). The expression of HLA-class II antigens is highly selective. Ectopic expression has been postulated to be responsible for autoimmune diseases. So it can be used as a specific marker for autoimmunity in DCM.

Adult↗
PubMed2001

HLA class II antigens positively and negatively associated with hepatosplenic schistosomiasis in a Chinese population.

To identify possible associations between host genetic factors and the onset of liver fibrosis following Schistosoma japonicum infection, the major histocompatibility class II alleles of 84 individuals living on an island (Jishan) endemic for schistosomiasis japonica in the Poyang Lake Region of Southern China were determined. Forty patients exhibiting advanced schistosomiasis, characterised by extensive liver fibrosis, and 44 age and sex-matched control subjects were assessed for the class II haplotypes HLA-DRB1 and HLA-DQB1. Two HLA-DRB1 alleles, HLA-DRB1*0901 (P=0.012) and *1302 (P=0.039), and two HLA-DQB1 alleles, HLA-DQB1*0303 (P=0.012) and *0609 (P=0.037), were found to be significantly associated with susceptibility to fibrosis. These associated DRB1 and DQB1 alleles are in very strong linkage disequilibrium, with DRB1*0901-DQB1*0303 and DRB1*1302-DQB1*0609 found as common haplotypes in this population. In contrast, the alleles HLA-DRB1*1501 (P=0.025) and HLA-DQB1*0601 (P=0.022) were found to be associated with resistance to hepatosplenic disease. Moreover, the alleles DQB1*0303 and DRB1*0901 did not increase susceptibility in the presence of DQB1*0601, indicating that DQB1*0601 is dominant over DQB1*0303 and DRB1*0901. The study has thus identified both positive and negative associations between HLA class II alleles and the risk of individuals developing moderate to severe liver fibrosis following schistosome infection.

Adult↗
PubMed1999

Towards understanding the origin and dispersal of Austronesians in the Solomon Sea: HLA class II polymorphism in eight distinct populations of Asia-Oceania.

HLA class II nucleotide sequence polymorphisms were examined in eight ethnic groups of Asia-Oceania using DNA typing methods. Allele frequencies and characteristic DR/DQ haplotypes were determined and compared with those of other populations of Asia-Oceania. Genetic distances were measured to show the genetic relationship within the studied populations as well as between the studied populations and previously published populations. Phylogenetic trees were constructed based on HLA allele frequencies using the neighbour-joining method. The populations, mainly Trobriand Islanders, Roro, Tolai, Western Samoans and Taiwanese Aborigines, are characterized by a reduced diversity at the HLA loci examined, especially for DPB1. The high frequency of the 'Asian'-specific DPB1*0501 allele in Trobrianders and Roro, but also in Western Samoans and Taiwanese Aborigines, was the most striking result. The prevalence of DPB1*0501 and the short genetic distance from Trobriander and Roro to Taiwanese Aborigines provide evidence that the origin of the Austronesian odyssey is south-east Asia, and Taiwan could be an important part of it. The relatedness of Trobrianders to the Polynesian population from Western Samoa indicates a probable recent common ancestor. The observed lack of diversity may reflect bottleneck(s) and/or limited diversity of the founding population. Analysis of HLA class I antigens, together with mt-DNA and Y-chromosomal studies, will give us further information about the settlement of the Trobriand and other islands during the colonization of the Pacific.

Alleles↗
PubMed1995

Molecular analysis of HLA class II genes in Goodpasture's disease.

A molecular analysis of HLA class II genes was undertaken in order to characterize the previously reported association between HLA-DR2 and glomerulonephritis caused by antibodies to glomerular basement membrane (Goodpasture's disease). Genomic DNA was prepared from 53 patients with Goodpasture's disease and analysed by: (i) Southern blotting using cDNA probes to DRB, DQA and DQB genes, after digestion with TaqI endonuclease; (ii) allele-specific oligonucleotide probing of specifically amplified DNA; and (iii) nucleotide sequencing of relevant alleles. The patients had a greatly increased frequency of DRw15 (a subspecificity of DR2) which was present in 75.5% of patients and 31% of controls (p < 0.0001). The frequency of DR4 was also increased, especially in patients without DRw15. Overall, 90.5% of the patients had either DRw15 or DR4. In contrast, the frequency of DR1 was significantly reduced (patients 5.6%, controls 20.7%, p < 0.01). Differences in the frequencies of DQA and DQB alleles could all be explained by linkage disequilibrium. Nucleotide sequences of relevant alleles were identical to those previously published. Comparison of derived amino acid sequences of expressed DR beta chains showed that the DR beta chains of DRw15 and DR4 shared a six-amino-acid motif from positions 26-31, that included four polymorphic amino acids none of which are shared with DR1. A sequence-specific oligonucleotide detected this amino-acid motif in 45/49 (91.8%) patients tested. Thus, this particular motif, which lies on the floor of the antigen binding groove, has a stronger association with Goodpasture's disease than any individual allele, and may be of pathogenic significance.

Alleles↗
PubMed2006

Lack of association of HLA class II alleles with peanut allergy.

BACKGROUND: Peanut allergy is a common and severe phenotype of food allergy with a strong genetic component; HLA class II polymorphisms are attractive candidate genes for this disorder. OBJECTIVE: To determine possible genotypic associations of HLA class II with peanut allergy and attempt replication of previously reported associations. METHODS: Sibling pairs discordant for peanut allergy were genotyped (low resolution) by polymerase chain reaction-based methods to 7 DQ and 18 DR allele groups. A chi2 analysis was undertaken against sibling controls with statistical adjustment for multiple analyses. RESULTS: Seventy-three children with confirmed peanut allergy (mean age, 6.5 years; male, 72%; asthma, 58%; atopic dermatitis, 62%; allergic rhinitis, 67%; other food allergies, 41%) and 75 of their siblings who eat peanut (mean age, 8 years; male, 52%; asthma, 12%; atopic dermatitis, 22%; allergic rhinitis, 37%; other food allergy, 7%) were genotyped. Distribution of DQ7 (29% of children with peanut allergy vs 47% sibling controls) was statistically significantly different (P = .04) before statistical correction for multiple comparisons was made by multiplying them by the number of alleles tested (and not statistically significant after correction; P = .30). Distribution of DR11 was nearly statistically significant without statistical adjustment (26% with peanut allergy vs 41% of sibling controls; P = .07; corrected P = 1.3). Alleles that were previously reported to have a weak association with peanut allergy (DRB1 *03, *08; DQB1 *0302, *04) were not verified in this cohort (unadjusted P > .44). CONCLUSIONS: We could not establish an association between the HLA class II alleles evaluated in this cohort of sibling pairs discordant for peanut allergy.

Child↗
PubMed1999

Genetic linkage of HLA-class II locus to mite-specific IgE immune responsiveness.

BACKGROUND: IgE response to common inhalant allergens seems to be the major determinant of the development of atopic rhinitis and asthma but it has been difficult to demonstrate genetic control of the IgE response. OBJECTIVE: To investigate genetic linkage between specific IgE reactions to purified aero-allergens (grass, birch, cat, mite) and the HLA-class II locus. METHODS: DNA-based HLA-class II typing was performed for determination of DRB1, DQB1 and DPB1 alleles. Linkage was studied by the affected sibpair method and the extended transmission disequilibrium test in 100 children from 40 nuclear families selected from a homogeneous population in south-western Germany. RESULTS: Significant linkage of mite-specific IgE response to HLA-DPB (P = 0.00001), HLA-DRB (0.02) and HLA-DQB (P = 0.001) was revealed by sibpair analysis of MHC class II alleles and confirmed by the extended transmission disequilibrium test for HLA-DRB (P = 0.01) and HLA-DPB (P = 0.04). No consistent significant linkage between the HLA-class II locus and IgE response to grass pollen, birch pollen, and cat dander could be demonstrated. CONCLUSION: The findings are consistent with the existence of one or more genes in the HLA-class II region modifying the IgE immune response to common environmental allergens.

Adolescent↗
PubMed1989

A method of HLA class II typing using nonradioactive labelled oligonucleotides.

The typing of HLA class II genes using molecular biology techniques has brought undoubtedly new insights in the analysis of their polymorphism. Particularly interesting is the dot-blot analysis of enzymatically-amplified genomic DNA hybridized with sequence-specific oligonucleotides. In order to use this technique of typing on a routine basis, we established a non-radioactive detection method of enzymatically-amplified genomic DNA dot-blots. We could clearly demonstrate that, using biotin-labelled specific oligonucleotides, it was possible to specifically discriminate between DQB1 first domain DNA sequences displaying three, two or even only one base-pair difference at a given codon position. The very satisfactory sensitivity level reached by this non-radioactive detection method could safely allow its use for clinical applications of HLA typing at the DNA level.

DNA↗
PubMed2003

Influence of HLA class II molecules on the outcome of hepatitis B virus infection in population of Zhejiang Province in China.

OBJECTIVE: To investigate the correlation between HLA class II molecules and the different outcome of viral hepatitis B. METHODS: Thirty patients with chronic hepatitis B and 56 subjects who had spontaneously recovered from HBV infection in Zhejiang were enrolled in this investigation. HLA class II molecules types and alleles were determined by PCR-ssp. RESULTS: HLA-DR12 was found in 21 of the 56 subjects (38%) recovered from hepatitis B, compared to 3 of the 30 patients with chronic hepatitis B [10%, relative risk (rr), 0.19; Pcorr<0.025]. The frequency of the allele of HLA-DR12 DRB1*1201 was higher in the subjects recovered from hepatitis B infection (32%) than in the patients with chronic hepatitis B (3%; rr, 0.07; Pcorr<0.005). On the contrary, more HLA-DR9 was detected in the patients with chronic hepatitis B (43%) than in the subjects who recovered from hepatitis B infection (18%; rr, 3.52; Pcorr<0.025). HLA-DQ9 was also detected with a higher frequency in the patients with chronic hepatitis B (43%) than in the subjects who recovered from hepatitis B (20%; rr, 3.13; Pcorr<0.05). CONCLUSIONS: The HLA class II molecule DR12 and its allele DRB1*1201 are associated with protection against chronic hepatitis B in Zhejiang Province, China. HLA-DR9 and DQ9 are associated with chronicity of HBV infection.

Adult↗
PubMed1994

HLA class II associations with idiopathic nephrotic syndrome in children.

The occasional familial occurrence of idiopathic nephrotic syndrome (NS) points to a genetic predisposition. Reports on associations with certain HLA class II antigens support this hypothesis. In order to define the immunogenetic background of NS more precisely, HLA class II allele frequencies in 161 children with NS were studied by restriction fragment length polymorphism (RFLP) typing. The patient cohorts consisted of 87 children from Southwest-France and 74 from Southwest-Germany. The control group consisted of 118 French and 101 German unrelated individuals from the same geographical areas. HLA alleles were defined in patients with steroid-sensitive (SS) and steroid-resistant (SR) NS and in controls. RFLP typing revealed that the previously reported association between SSNS and HLA-DR7 is confined to the RFLP split 7.1 (DRB1*07) with a combined relative risk (RRcomb) of 6.2. HLA-DQB typing showed an increased frequency of the allele DQB2b (DQB1*0201) (RRcomb = 7.8). HLA-DQA typing showed an association of SSNS with DQA3 (DQA1*0201,0301,0302) (RRcomb = 4.1). The highest RR (16.5) for SSNS was found in German patients who carried the two DRB1 specificities 17.1 (DRB1*0301) and 7.1 (DRB1*07). All associations were stronger in SS patients with frequent relapses or steroid dependency than in non- or infrequent relapsers. SR patients exhibited no significant associations with HLA class II alleles.

Alleles↗
PubMed1986

Differential expression of HLA class II antigens in fetal human spleen: relationship of HLA-DP, DQ, and DR to immunoglobulin expression.

Frozen sections of human fetal spleen from 12 to 20 wk gestation were examined by using polyclonal antibodies to Ig isotypes, monoclonal antibodies to HLA class II subregion locus products, B and T cells, and follicular dendritic cells. Scattered lymphoid cells in spleen sections from fetuses of 12 to 13 wk gestational age expressed IgM but not IgD. The appearance of lymphoid cells expressing IgD occurred at 14 to 15 wk before the formation of loose clusters of B cells at 16 wk. IgD expression was associated mainly with cells in these clusters, which by 17 wk had become definite follicles. Follicular dendritic cells were not detectable until 20 wk. OKT3-positive T cells were not detected until 17 wk, and at 20 wk constituted 5% of the nucleated cell population. HLA-DR- and DP-positive lymphocytes and macrophages were detectable in fetal spleen from 12 wk onward; DR was expressed on more cells than DP, and the numbers of cells stained by HLA-DR-specific monoclonal antibodies exceeded the number of Ig-positive cells in all spleens examined. HLA-DQ was expressed by consistently fewer cells than HLA-DR and -DP in all spleens tested. The small number of DQ-positive cells in spleens from 12- to 13-wk fetuses had the morphology of macrophages; HLA-DQ expression by lymphoid cells followed a similar pattern to IgD expression and was associated mainly with follicular lymphocytes. It could be demonstrated by double-labeling experiments that all follicular IgM-positive cells in 17- to 20-wk spleens expressed HLA-DP, DQ, and DR antigens: IgM-positive cells in 12- to 16-wk spleens and interfollicular IgM-positive cells in 17- to 20-wk spleens all expressed HLA-DR, but only 59% and 43% expressed DP and DQ, respectively. Ninety-one to 100% of IgD-positive cells in all spleens examined expressed HLA-DQ in addition to DR and DP. In these experiments IgD-negative, DQ-positive cells had the morphologic appearance characteristic of macrophages. These data suggest that class II antigens are differentially expressed on developing lymphoid cells; DR and DP expression occurring in the earliest spleens examined, with expression of DP on a subpopulation of DR-positive cells; IgD and DQ expression appears to be coincident on maturing B cells as they begin to form follicles. An immunoregulatory role for HLA-DQ in B cell development is implicated and remains to be fully investigated.

Antibodies, Monoclonal↗
PubMed1993

Association of insulin-dependent diabetes mellitus in Taiwan with HLA class II DQB1 and DRB1 alleles.

The allelic constitution at HLA class II DRB1, DQB1, DQA1, and DPB1 loci of IDDM patients from Taiwan was compared with that of ethnically matched nondiabetic individuals by PCR-based DNA typing. Of the three haplotypes found to be positively associated with IDDM in Taiwan, two (DRB1*0301-DQA1*0501-DQB1*0201 and DR4-DQA1*0301-DQB1*0302) appear to be identical to the susceptible haplotypes in Caucasian and black populations, whereas the third haplotype (DR4-DQA1*0301-DQB1*04) has been reported to be positively associated with IDDM only in the Japanese population. The three haplotypes, DRB1*1502-DQA1*0102-DQB1*0601 and DRB1*1201 (or 1202)-DQA1*0501-DQB1*0301 and DRB1*0803-DQA1*0103-DQB1*0601, were negatively associated with IDDM in Taiwan; a protective effect of the last haplotype has not been reported previously. Neither DQ beta non-Asp-57 nor DQA1*0301 alone appears sufficient to account for the HLA-associated susceptibility to IDDM in Taiwan. Also, the DQ alpha beta heterodimer encoded by the alleles DQA1*0301/DQB1*0201, DQA1*0301/DQB1*0302, or DQA1*0501/DQB1*0201 does not explain the susceptibility of a larger fraction of the IDDM patients than the residue at position 57 of the DQ beta chain or DQA1*0301. Finally, the DRB1 alleles appear to affect IDDM susceptibility, although for most haplotypes the effect of individual loci cannot be assessed due to the linkage disequilibrium between the DQ and the DR region.

Adult↗
PubMed1989

HLA class II polymorphism: implications for genetic susceptibility to autoimmune disease.

Our understanding of HLA class II polymorphism has undergone a rapid evolution in the last few years. As in so many areas of modern biology, this progress has depended largely on the application of recombinant DNA techniques to the study of this gene family. In particular, the recent development of methods of gene amplification by means of the polymerase chain reaction has allowed for the rapid assessment of polymorphism in the human population. In addition, the elucidation by x-ray crystallographic analysis of the three-dimensional structure of an HLA molecule has been a major step. These areas of progress have now begun to converge to allow a more detailed approach to the problem of class II polymorphism and disease susceptibility. As discussed in this review, the data so far indicate that a few amino acid substitutions in class II molecules may exert a critical influence on susceptibility to autoimmune diseases such as RA and IDDM. The mechanism by which these class II polymorphisms predispose to autoimmune disease is still unknown. It is tempting to speculate that differences in the binding affinity of HLA molecules for autoantigens might be involved; however, as yet no specific autoantigen has been identified for either RA or IDDM. Intriguingly, sequence similarities have been observed between some viral proteins and class II molecules, raising the possibility that these infectious agents might induce autoimmunity by "molecular mimicry." Examples include the human cytomegalovirus protein, IE2 as well as the Epstein Barr virus gp110 protein. Other possible mechanisms involve more complex immunoregulatory effects, such as the absence of suppressor functions that appear to be under the influence of the HLA genes. To some extent, the persistent ignorance about the cause of autoimmunity reflects a general lack of knowledge concerning exactly how HLA polymorphisms exert immunoregulatory effects. For example, in addition to influencing antigen presentation, MHC molecules also affect the overall T cell repertoire during thymic selection. The relative importance of HLA class II polymorphism in exerting immunoregulatory effects by means of thymic selection of the T cell repertoire is unknown. For autoimmune diseases such as RA and IDDM, there is a need to identify a specific functional abnormality that is causing the disease before the etiological significance of the emerging associations with class II polymorphisms become clear.(ABSTRACT TRUNCATED AT 400 WORDS)

Alleles↗
PubMed2004

HLA class II polymorphism in Egyptian children with lymphomas.

UNLABELLED: The major histocompatibility complex (MHC) is a set of closely-linked genes encoded on the short arm of chromosome 6. It is important for understanding human immunological diseases, transplantation and in host defense against infection. The membrane proteins are two types; class I MHC proteins and class II MHC proteins. Strong arguments supporting genetic linkage between susceptibility to lymphomas and human leukocyte antigens (HLA)-class II are reported and give a clue about susceptibility or protection from the disease. AIM: To evaluate the possible changes of HLA class II (DR, DQ) alleles in children with lymphoma. METHODS: Thirty cases were included in this limited study. Nineteen cases of non Hodgkin's lymphoma (NHL) and eleven patients with Hodgkin's lymphoma (HD). Their ages ranged from 1.5 to 15 years. The control group consisted of 121 unrelated healthy subjects for DRB1 alleles and 59 unrelated healthy subjects for DQB1 alleles (only 59 subjects were typed for both DRB1 and DQB1). All cases in the study were assessed by thorough history taking, physical examination and laboratory investigations that included complete blood count, renal function tests, liver function tests, serum uric acid and HLA typing. Patients and controls were typed for HLA class II DRB1 and DQB1 alleles using INNO-LIPA reverse hybridization line probe assay (Innogenetic, Belgium). RESULTS: HLA-DRB1 *0403 and *1301 and HLA-DQB1 *0501,* 0201 and *0301 were significantly increased in patients with NHL when compared with control; whereas HLA-DRB1 *1302 and HLA-DQB1 *0502 and *0602 were significantly decreased when compared with control. In patients with HD, HLA-DRB1 *0403 and *1202 and HLA-DQB1 *0604, *0201 and *0203 were significantly increased when compared with control. CONCLUSIONS: (1) The susceptibility to NHL is related to HLA-DRB1 *0403 and *1301 and HLA-DQB1 *0501,* 0201 and *0301. (2) The susceptibility to HD is related to HLA-DRB1 *0403 and *1202 and HLA-DQB1 *0604, *0201 and *0203. (3) HLA-DRB1 *1302 and HLA-DQB1 *0502 and *0602 may confer protection to NHL. (4) Different HLA alleles may have a role in patients with both groups of lymphoma and further study is needed to better define the possible prognostic value of different HLA associations in patients with lymphomas regarding increased risk in the presence of certain HLA alleles and the possibility for treatment modifications in the future based on the presence or absence of certain HLA alleles.

Child↗
PubMed1991

Alleles at four HLA class II loci determined by oligonucleotide hybridization and their associations in five ethnic groups.

The use of polymerase chain reaction (PCR) and oligonucleotide hybridization offers a new approach for the definition of HLA class II alleles. It has been possible to determine 43 alleles of DRB1, four of DRB3, two of DRB4, four of DRB5, eight of DQA1, and 14 of DQB1. These alleles are inherited together in members of families and form closely associated groups which are found repeatedly and in characteristic patterns in different populations. We have determined the HLA class II alleles and analyzed their association in 431 healthy unrelated subjects including 161 North American Caucasians, 53 Latin Americans, 61 Blacks, 88 Chinese, and 68 Israeli Jews. For-locus haplotypes (DRB1; DRB3/4/5; DQA1; DQB1) were derived from 79 B cell lines and the analysis of segregation in 34 nuclear families. The B-cell lines yielded 37 and the families showed the same, and 20 other, haplotypic combinations. In addition to these 57 haplotypes, associated alleles were assigned in the unrelated panels following certain rules. The resulting haplotypes were assigned to groups known to share associated alleles. The groups were: 1) DR1, DR2, and DRw10 (13 haplotypes); 2) DR3 and DRw6 (26 haplotypes); 3) DR5 and DRw8 (24 haplotypes); 4) DR4, DR7, and DR9 (24 haplotypes). Their distribution in populations with different ethnic backgrounds was analyzed. The expressed DRB4 allele and its null mutant were determined by PCR and oligonucleotide hybridization. The different DR7 haplotypes resulting from these determinations were analyzed in a panel of 130 North American Caucasoids. This comprehensive analysis of class II HLA haplotypes in human populations should be useful in understanding the role of these genes and in various applications including anthropology, disease susceptibility, and transplantation of allogeneic organs and tissues.

Alleles↗
PubMed2001

The association of HLA class II with pars planitis.

PURPOSE: To investigate the association of HLA class II alleles with pars planitis. METHODS: Blood samples were obtained from 28 patients with pars planitis seen in the Department of Ophthalmology and Visual Sciences and the Barnes Retina Institute at Washington University, St. Louis, Missouri. RESULTS: HLA-DR15, one of the allelic subtypes of HLA-DR2, was present in 18 (64.3%) of 28 patients vs. 10 (20%) of 50 controls (OR = 7.20, CI = 2.28--23.20, P =.0001). HLA-DR51 (HLA-DRB 5) was present in 16 (57.1%) of 28 patients vs. 6 (12%) of 50 controls (OR = 9.78, CI = 2.79--36.42, P =.0001). HLA-DR17 was present in eight (28.6%) of 28 patients vs. one (2%) of 50 controls (OR = 19.60, CI = 2.29--886.7, P =.0001). CONCLUSION: Pars planitis is associated with an increased frequency of the HLA-DR2 suballele, -DR15, HLA-DR51, and HLA-DR17. These results suggest an immunogenic predisposition exists to pars planitis.

Adolescent↗
PubMed2001

Association and linkage of leprosy phenotypes with HLA class II and tumour necrosis factor genes.

Previous analyses indicate major gene control of susceptibility to leprosy per se and the HLA class II region has been implicated in determining susceptibility and control of clinical phenotype. Segregation analysis using data from 76 Brazilian leprosy multi-case pedigrees (1166 individuals) supported a two locus model as the best fit: a recessive major gene and a recessive modifier gene(s) (single locus vs two locus model, P = 0.0007). Combined segregation and linkage analysis to the major locus, showed strong linkage to HLA class II (HLA-DQB1 P = 0.000002, HLA-DQA1 P = 0.000002, HLA-DRB1 P = 0.0000003) and tumour necrosis factor genes (TNF P = 0.00002, LTA P = 0.003). Extended transmission disequilibrium testing, using multiple affected family members, demonstrated that the common allele TNF*1 of the -308 promoter region polymorphism showed linkage and/or association with disease per se, at a high level of significance (P < 0.0001). Two locus transmission disequilibrium testing suggested susceptibility (TNF*1/LTA*2) and protective (TNF*2/LTA*2) haplotypes in the class iii region. Taken together the segregation and HLA analyses suggest the possibility of more than one susceptibility locus in the MHC.

Brazil↗