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W Ollier

Publications and source records attributed to W Ollier.

At least 73 records · Page 4Linked to original sources

HLA-DR4 associated Dw types in rheumatoid arthritis.

Frequencies of HLA-DR4 and its related Dw types were compared between randomly selected normal controls and the index cases of multiplex rheumatoid arthritis (RA) families. A DR4 frequency of 68.3% was observed in index cases (n = 57) compared to 31.2% in normal controls (n = 96). Cellular typing with homozygous typing cells (HTCs) revealed significant increases of Dw4 (49.1% vs 22.9% RR = 3.2 p less than 0.001) and Dw14 (22.8% vs 2.1% RR = 13.9 p less than 0.001) in the index cases. A non-significant increase was seen for Dw13 (8.8% vs 4.1%). When DR4 positive patients and controls were compared, a significant increase was seen only for Dw14 (34.2% vs 6.6% RR = 7.3 p less than 0.01). Data from HLA genotyped RA and normal families allowed an examination of haplotype combinations of HLA-B antigens and DR4/Dw types to be made. HLA-Dw4 was predominantly found with B44 and Bw62 with nearly all DR4/Bw62 haplotypes being Dw4 positive. HLA-Dw13 was associated with B44 and Dw14 with Bw60, B44 and B27. Based on HTC and normal family data. Dw10 was found to be strongly associated with B38 containing haplotypes. Analysis of 69 C4A, C4B complement typed DR4 haplotypes failed to show any statistically significant association between Dw type and "complotype". However, there was a suggestion of C4A3. BQO being associated with Dw4 (34.2% vs 16.1% X2 = 2.9 p = ns) and C4A3, B1 with Dw14 (45.5% vs 27.6% X2 = 2.1 p = ns).(ABSTRACT TRUNCATED AT 250 WORDS)

Arthritis, Rheumatoid↗

HLA-D region heterogeneity in a Nigerian population.

HLA class II antigens were studied in a panel of 130 Nigerians. Complex patterns of associations were seen between HLA-Dw, -DR and -DQ specificities, differing widely from those reported for other populations. A number of Dw types were associated with the same DR antigen: Dw'1N' and Dw'BERN' with DR1, Dw2 and Dw'2N' with DR2, Dw5 and Dw'5N' (Dw5 + Dw'F5') with DRw11. It was also observed that a Dw type associated with more than one DR antigen: HLA-Dw3 was assigned to individuals who were DR3 negative and similarly Dw10, Dw13 and Dw14 to individuals negative for DR4. HLA-DRw8 and Dw8 were completely dissociated in Nigerians, and Dw8 did not show a preferential DR association. These results demonstrate that DR and DQ identity between HTC stimulator and responder cell is not necessarily a prerequisite for Dw to be assigned. Preliminary studies show that subtypes of HLA-Dw1 and Dw8 detected by HTC typing correlate with restriction fragment length polymorphisms (RFLPs) detected with a combination of Bgl II enzyme and DRA/DRB cDNA probes. HLA-DP antigen frequencies differed between Nigerians and British Caucasoids. The most common DP antigen in Nigerians was DPw1, compared with DPw4 in Caucasoids. HLA-DPw6 appeared to be absent or rare in both Nigerians and British Caucasoids. Only five out of 68 Nigerians tested were assigned two DP specificities. The association between HLA-DR3 and DPw1 reported in Caucasoid panels was absent in Nigerians.

Black People↗

HLA antigen and haplotype frequencies in Greeks.

A random panel of 189 healthy Greek subjects was HLA typed for A, B and DR antigens. The alleles of these loci were found to be in Hardy-Weinberg equilibrium. Compared with other European Caucasoid populations, the frequencies of A9, B5, B18, B35, DR2 and DR5 were raised and that of B8 lowered. Significant linkage disequilibrium was found between a number of A/B, B/DR and A/DR antigen combinations. Some of the antigen associations usually seen in Caucasoid populations were also present in this sample (A1-B8-DR3, B14-DR1, B15-DR4) although others were missing (A3-B7-DR2, B35-DR1, B44-DR4). In addition, some antigen combinations have not been previously described. The most frequent two locus haplotypes in the Greek population are B8-DR3 and B18-DR5.

Alleles↗

Antigenic determinants expressed by human C4 allotypes; a study of 325 families provides evidence for the structural antigenic model.

The antigenic determinants of human C4 have been defined by human IgG antisera, Rodgers (Rg) and Chido (Ch), in hemagglutination-inhibition assays (HAI). Eight (2 Rg and 6 Ch) are of high frequency, greater than 90%, and 1, WH, is of low frequency, 15%. The phenotypic combinations are complex; generally, C4A expresses Rg, and C4B has Ch, but reverse antigenicities have been established both by HAI and by sequence data of selected C4 allotypes. A study of 325 families provides data on the antigenic expression of each C4 allotype and demonstrates strong associations. A structural model for the antigenic determinants of C4 proteins has been proposed and is completely supported by the family material. Of the 16 possible antigenic combinations for C4 proteins, only 3 are undetected. A new Ch combination has been recorded in two French families. The reported sequence variation within the C4d region can account for the antigenic determinants but leaves the location of electrophoretic variation in C4 still unclear.

Blood Group Antigens↗

Chromosome 14 markers in rheumatoid arthritis.

Phenotype frequencies for variants of the chromosome 14 markers, alpha 1 antitrypsin (protease inhibitor--Pi), and immunoglobulin heavy chain gene allotypes (Gm and Am) were examined in affected and unaffected members of multicase rheumatoid arthritis (RA) families and compared with published population data. Significantly higher frequencies of phenotypes containing Pi*Z and Pi*S were observed in unrelated index RA cases compared with UK population data. There was also a higher frequency of Pi*Z in family members without RA than in population controls but no such difference for the frequency of Pi*S. No difference in the frequency of PiM1M2 heterozygotes was seen between patients with RA and population controls. An examination of clinical data failed to show any relation between any particular feature of RA and positivity for Pi*Z or Pi*S. No significant differences in frequency of Gm phenotypes were observed between patients with RA and controls. Significant association was found, however, between Pi*Z and Gm phenotypes containing Gm(zax;g). These associations are interpreted as indicating linkage disequilibria between these alleles. No interactions between DR4 and either G1m(z), (a), or (x) allotypes were apparent in patients with RA. A significant association was seen in the index RA cases between DR4 and Pi phenotypes carrying Z or S alleles. Observations from this study provide evidence for the existence of a genetic component for RA susceptibility encoded on chromosome 14. An interactive effect of these genes with DR4 towards susceptibility appears likely.

Arthritis, Rheumatoid↗

HLA-Dw specificity assignments are independent of HLA-DQ, HLA-DR, and other class II specificities and define a biologically important segregant series which strongly activates a functionally distinct T cell subset.

Several lines of evidence indicate that HLA-Dw, as defined by HTC typing, is not the result of the combined stimulatory effect of HLA-DR and DQ. Therefore, responder cells do not have to share HLA-DQ antigens with the stimulator HTCs to give a typing response. The common HLA-DR-DQ associations observed in HTCs correspond to different patterns of linkage disequilibrium in different populations. HLA-DQ and HLA-Dw are functionally heterogeneous. Although HLA-DQ molecules may play a role in primary stimulation, this role is distinct from that of Dw determinants which have strong lymphocyte activating properties. The role of the HLA-DQ determinants on the other hand, is one of modulating the total T cell response by controlling the proliferation of suppressor and cytotoxic cells. The primary MLC response is the result of the proliferative effect of HLA-Dw, DR, DP, and other associated determinants, in conjunction with a modulatory effect of DQ molecules. However, HLA-Dw (as detected by HTC typing) are DR associated determinants which are immunodominant in primary MLR. The genes of the HLA-DR subregion have been named DR by the WHO nomenclature committee. This subregion encodes the HLA-DR specificities and the DRw52 and DRw53 determinants. Unfortunately this nomenclature does not take into account the need to define the genetic basis of the HLA-Dw determinants--whether they are encoded by separate genes within the HLA-DR subregion or whether they are encoded by as yet unspecified genes in the HLA class II region in linkage disequilibrium with HLA-DR DRw52/53. There are at least three and possibly four beta chain genes in the HLA-DR subregion, all in strong linkage disequilibrium with each other. Some of these are expressed in most haplotypes while others are not; some behave as pseudogenes in some haplotypes and in others, all the genes are expressed. All the genes of the class II region have not been fully characterized. HLA-Dw determinants may be specified by one or more of these genes. When more information becomes available, the genetic and molecular basis of the HLA-Dw series as well as the functional heterogeneity and antigenic strength of the various class II determinants will be better understood.

Epitopes↗

HLA and rheumatoid arthritis: a combined analysis of 440 British patients.

Four hundred and forty unrelated British Caucasoid patients with rheumatoid arthritis (RA) have been HLA typed for class I and class II antigens. Analyses of HLA antigen associations were performed on the overall group and in patient subsets selected according to particular disease parameters or sex, or both. The results confirm previously reported positive associations of HLA-DR4, Dw4, and DRw53 and negative associations of HLA-DR2 and DR7 with RA. Patients subsets with severe erosions, seropositivity, and features of extra-articular disease showed a stronger association, also confirming earlier reports. The link between HLA and disease severity was emphasised by a significant trend of increased Dw4 frequency with increasing severity of radiological erosions. In addition, a positive association of RA with HLA-A2 was observed and a strong negative association with DR3. The frequency of HLA-B27 was significantly increased in patients with subluxation of the spine. Differences were observed between male and female patients in relation to the HLA association. In men an increase in the frequency of the haplotype HLA/Dw4/DR4/Bw62/Cw3/A2 was observed. This showed no relationship with parameters of disease severity other than extra-articular disease. In women only class II antigens (DRw53/Dw4/DR4) showed an increased frequency. This increase was strongly associated with disease severity. A significant decrease of this class II association was observed with increasing age of disease onset; this was not seen in men.

Adolescent↗

New HLA DNA polymorphisms associated with rheumatoid arthritis.

Studies of restriction enzyme fragment length polymorphisms (RFLP) have further clarified two DNA polymorphisms detected in DR4 positive individuals with a DQ beta probe. These patterns have been designated DQ beta omega, characterized in the Dw4 homozygous typing cell (HTC) BM14 and DQ beta phi, characterized in the Dw4 HTC MCF, and so do not correspond with different Dw types. These patterns clearly segregate in families with HLA haplotypes. We suggest that omega and phi may be polymorphisms of the DX beta gene. The previously reported DX alpha polymorphisms U and L were found with all DR types and in association with DQ beta omega (U) and DQ beta phi(L). In addition DQ beta phi was found to be strongly associated with TA10 positively (a subdivision of DQw3) although this association was not absolute. Associations between RFLP and other HLA Class II and I antigens seen in DR4 patients and DR4 controls suggest the existence of at least two preferential allelic associations (PAA), one containing omega/U and the other phi/L. PAA1: DX alpha U-DQ beta omega-TA10 negative-DQw3-Dw4-DR4----Bw62-Bw6-Cw3-A2 PAA2: DX alpha L-DQ beta phi-TA10 positive-DQw3-Dw4-DR4----B44-Bw4-Cw3-A2 The frequency of the omega pattern was higher, although not significantly in the RA patients compared with controls. However, a significantly higher frequency of omega was found in RA patients with extra-articular manifestations (EA) compared (a) with controls (p less than 0.04) and (h) with those patients without EA (p less than 0.05). In addition the frequency of phi was significantly higher in RA patients with nodules and/or erosions (N/ER) compared with patients without these features (p less than 0.008). When cumulative scores were assigned to patients after assessing the number of components fulfilled for each PAA, PAA1 appeared to be pronounced in patients with EA and PAA2 in patients with N/ER. The frequency of a previously reported DQ beta T6 band found with the enzyme Taq 1 and DQ-beta probe was found at a higher frequency in RA patients compared with controls. In addition a significantly higher frequency of this band was found in female RA patients compared to males.

Arthritis, Rheumatoid↗

HLA and rheumatoid arthritis: an analysis of multicase families.

In a study of multicase RA families, significantly raised frequencies of the HLA antigens DR4, DR1, Bw62, Cw3, A2, A31 and significantly lower frequencies of DR2, DR3, and B8 were found in probands compared to normal controls. When haplotype frequencies were compared between probands and controls, two haplotypes A2-B44-DR4 and A2-Bw62-DR4 were at higher frequency in probands. These differences no longer reached significance when only DR4-containing haplotypes were compared between probands and controls. A significantly lower haplotype frequency of A1-B8-DR3 was observed in probands compared to controls. This difference did not remain significant when only non-DR4 haplotypes were compared. Using an affected sibling pair ratio method, significant linkage between HLA and RA was found (P less than 0.01). Significant linkage was also observed between HLA and seropositivity. Analysis of Hardy-Weinberg equilibrium for the DR locus did not support the suggestion that DR4-associated RA susceptibility was inherited as a dominant trait. In addition it did not support the notion of an additive effect of DR4 and DR1 in RA susceptibility as these antigens were not found together more frequently than predicted by their individual gene frequencies.

Arthritis, Rheumatoid↗

A multicase family study of rheumatoid arthritis in south west Ireland.

A study of 26 families with multiple cases of RA was conducted in South West Ireland. In 149 relatives examined, 67 cases of RA were identified. An analysis of affected sibling pairs and trios revealed significant linkage between HLA and RA (p less than 0.05). A high frequency of DR4 was observed in probands (80.7 per cent) and affected members (74.6 per cent) compared with controls (18 per cent). An elevated frequency of the haplotypes A2-B44-DR4 (19.2 per cent) and A2-Bw62-DR4 (5.7 per cent) was seen in the affected sample. HLA-Bw62 was at raised frequency in probands (19.2 per cent) compared with controls (9 per cent). The haplotype frequency of A2-B44-DR4 was raised in affected females and A2-Bw62-DR4 in affected males. A low haplotype frequency of A1-B8-DR3 was found in all RA subjects. Disease severity (clinical and radiological criteria) was associated with DR4, but this did not reach statistical significance. A high incidence of extra-articular features of RA was observed, with DR4 occurring in all cases of vasculitis (75 per cent of whom were DR4 homozygous).

Adult↗

HLA and rheumatoid arthritis: susceptibility or severity?

An analysis of data collected on 440 British Caucasoid rheumatoid arthritis patients has confirmed positive association with HLA-DR4, Dw4, DRw53, and A2 and negative associations with HLA-DR2, 3, and 7. HLA-DR4 is more associated with RA 'severity' than with RA 'susceptibility', when measured by the parameters of ARA classification, seropositivity, severity of erosions and extra-articular manifestations. The association between HLA-A2, Cw3, Bw62, DR4, DRw53, and Dw4 and extra-articular disease has been confirmed in this study. The analysis of HLA and RA severity with respect to sex showed high frequencies of DR4, Dw4, and DRw53 in females, which increased in those with severe erosions, seropositivity or extra-articular disease. In males with RA, the disease appears to be associated not only with DR4, Dw4 and DRw53, but also with A2, Cw3 and Bw62. However, no significant differences in these antigen frequencies were found between male patients with severe RA and those without. Despite a significant decrease in the frequencies of DR3, B8 and A1 in most RA patient subsets, RA patients with Sjogren's syndrome showed a marked increase of A1 and B8 and patients with auto-antibodies had a significant increase in HLA-DR3 frequency when compared with patients without these features.

Arthritis, Rheumatoid↗

A new HLA Bw16 subtype defined in both Negroid and Saudi Arabian populations.

Serological identification of a new HLA-Bw16 subtype, B39B, was made by the analysis of reaction patterns of many alloantisera and one monoclonal antibody. The B39B pattern of reactivity was shown to be distinct from HLA-Bw38, Bw39, and 8w57. Cytotoxicity testing before and after absorption suggests that the B39B specificity belongs to the HLA-B7 cross-reactive group. The B39B was clearly demonstrated in two families. This antigen was detected in Negroids and Saudi Arabian Caucasoids but not in a large panel of British Caucasoids.

Black People↗

HLA polymorphisms in Saudi Arabs.

The HLA-A, -B, -C, -DR, Bf and GLO phenotypes of 109 unrelated Saudi Arab males have been determined. HLA-A and -B antigen frequencies were compared with data reported for European Caucasoids and various Arab populations. Most similarities in antigen frequencies were seen between Saudi Arab and Iraqi populations. A high frequency of Bw50 was observed in Saudi Arabs. The frequencies of HLA-DR antigens in Saudi Arabs were compared to European Caucasoids. HLA-DR7 was at high frequency in Saudi Arabs. Linkage disequilibria between alleles of HLA loci was examined. Many instances of previously reported antigen associations were seen in Saudi Arabs, together with a number of associations which have not been described elsewhere. HLA-Cw6-Bw50-DR7-BfS0.7 is suggested as being a common haplotype in Saudi Arabs.

Complement Factor B↗

HLA polymorphisms in a Shanghai Chinese population.

The frequencies of the HLA-A, B, C, D, DR and MB antigens have been determined in a homogeneous Shanghai Chinese population. Comparisons with the HLA-A and -B frequencies in other subsets of the Chinese population revealed some marked differences. No comparisons were possible for the D, DR and MB antigens since there were no previous studies of the antigens in those loci. We suggest that studies of the Chinese population should be confined to clearly defined homogeneous subsets. In this manner, the confounding effect of population heterogeneity may be avoided, and it is this heterogeneity which calls for extensive surveys of the huge Chinese population.

Asian People↗

HLA antigen associations with extra-articular rheumatoid arthritis.

Seventy-seven patients with rheumatoid arthritis were investigated to examine the frequency of HLA antigens and their relationship to clinical and serological manifestations of extra-articular disease. The phenotype frequencies of DR4, DRw53, Bw62 and Cw3 were significantly increased, compared to normal controls, and there were negative associations with DR2 and DR7. The HLA antigen in strongest association with rheumatoid arthritis was DR4 (73.6%) and the relationship with DRw53 appeared to be secondary. The frequency of DR4 rose to 92% in seropositive patients with extra-articular disease manifestations whose serum contained immune complexes. A high frequency of DR4 was also seen in male patients (86%), reaching 100% in the small group of seropositive male patients with immune complexes. It is suggested that extra-articular disease represents a manifestation of severe classical rheumatoid arthritis and is not an 'overlap' syndrome. We propose that the HLA haplotype Cw3-Bw62-Dw4-DR4-DRw53 makes a greater genetic contribution to disease susceptibility in both extra-articular and male rheumatoid arthritis patients than in other subsets of RA.

Arthritis, Rheumatoid↗

HLA-DB3: population distribution and family studies of a new HLA-D antigen associated with HLA-D antigen associated with HLA-DR4 in Caucasoids.

On the basis of studies with 6 HTCs in four different families the new cluster DB3 identified in the 8th Workshop can be considered an established specificity of the HLA-D series. In 112 healthy Caucasoids resident in South East England the frequency of this antigen was 2.6% similar to the frequency found in 142 Caucasoid patients with rheumatoid arthritis. The frequency in 54 unrelated Chinese individuals from Shanghai and of 120 Nigerians was 7.5% and 3%, respectively. All Caucasoid individuals who were DB3 were also DR4 whereas no such association was found in the two other population groups.

Asian People↗