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D Jaraquemada

Publications and source records attributed to D Jaraquemada.

At least 55 records · Page 3Linked to original sources
PubMed1986

HLA-DR4 as a predictor of outcome three years after onset of rheumatoid arthritis.

Data from 59 patients with early rheumatoid arthritis were analysed to determine the predictive value of the possession of HLA-DR4 for disease severity and functional outcome at 3 years after disease onset. The previously reported association of that antigen with seropositive disease was confirmed. Conversely, however, there was no evidence that functional outcome was worse in the HLA-DR4 positive group as measured by the Stanford Health Assessment Questionnaire. The mean articular index was lower in the HLA-DR4 group which also had a smaller proportion with limited wrist extension. In addition, both patient and physicians' global assessment of disease status were better in the HLA-DR4 group. It is concluded that HLA-DR4 is not a useful predictor of poor outcome at 3 years.

Adult↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1986

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↗
PubMed1985

Different functions and associations of HLA-DR and HLA-DQ(DC) antigens shown by serological, cellular and DNA assays.

Two consanguineous Caucasoid HTCs, DHI and FPA, were investigated, the latter having an unusual HLA-DR/DQ(DC) association. Both these HTCs typed clearly as HLA-DRw11. However, while DHI typed as DRw11/DQw3(DC4) as expected, FPA typed as DRw11/DQw1(DC1) instead. Although extremely rare in Caucasoids, DRw11/DQw1 is a common pattern of association in Nigerian Negroids. Southern blots of DNA extracted from EBV cell line derived from FPA, hybridized with HLA-DC alpha and HLA-DC beta probes, confirmed this unusual DRw11/DQw1(DC1) association. In addition the DC alpha probe showed a unique additional restriction fragment length polymorphism (8 kb) attributable to the DX gene in the FPA DNA. When DHI and FPA were used as stimulators in MLC, the patterns to typing responses obtained were not completely concordant although they overlap to some extent. For this reason FPA has been locally designated Dw'F5', distinct from Dw5. Furthermore, the HLA-DQ antigens of the responder cells were not necessarily the same as those of the HTCS to which they gave typing responses (FPA and DHI). Functional studies using these two HTCs showed that the DQ(DC) antigens probably have no direct lymphocyte activating properties but rather have a regulatory role in controlling responses to allodeterminants in MLC.

Antibodies, Monoclonal↗
PubMed1985

HLA polymorphisms in Nigerians.

The HLA class I and class II phenotypes of a panel of 114 unrelated Nigerians have been determined. The panel was tested for all the known class I antigens and comparisons of the HLA-A and -B frequencies with those of other African Negroid populations revealed some differences. Only limited comparisons could be made for the HLA-DR and -D frequencies as these are not available for any well-defined African Negroid population. The data concerning the class II antigens of this panel are the most interesting. Half of the DRw11-positive panel members are DQw3 negative and DQw1 positive. In addition, there is dissociation of some HLA-D and -DR specificities, a number of panel members are positive for an HLA-D specificity and are negative for the corresponding HLA-DR specificity. Our results show the value of population studies in the investigation of the relationship between the different HLA class II antigens.

Black People↗
PubMed1984

Association of HLA-DR4/Dw4 and DR2/Dw2 with radiologic changes in a prospective study of patients with rheumatoid arthritis. Preferential relationship with HLA-Dw rather than HLA-DR specificities.

Patients admitted to a prospective study within a year of onset of suspected rheumatoid arthritis showed a positive correlation between HLA-Dw4 and the eventual severity of peripheral radiologic changes. Dw4 and DR4 were strongly associated with severity of erosions when analysis was restricted to each of the following: patients with erosions, those under 50 at onset, and all females. Relationships were consistently stronger with Dw4 than with DR4. Another D-related specificity, MT3, was positively correlated and Dw2/DR2 negatively correlated with erosions.

Age Factors↗
PubMed1984

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↗
PubMed1984

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↗
PubMed1983

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↗
PubMed1981

MHC specified lymphocyte activating and suppressor activating determinants in human mixed lymphocyte reactions.

We have shown (1) the presence of HLA-linked Sad/s on a homozygous typing cell (HTC), FPA (8W321). When we used it to type the P family, which included an HLA-B/DR recombinant sibling, its genes mapped towards the HLA-B-A end of the HLA haplotype separate from HLA-D/DR and was found to be associated with HLA-Bw35 homozygosity; (2) this same recombinant maps the C4 complement genes on the HLA-D/DR end of the chromosome away from HLA-B; (3) that the suppressor T cell subpopulation which was activated by the Sad of this consanguineous HTC FPA was left behind after separating the OKT4 positive cells with a monomorphic monoclonal anti-T-cell antibody (OKT4). These OKT4 positive cells reacted normally in MLC to the FPA Lad Fes 6; (4) that at least part of the genetic control of suppressor recognition is outside the HLA complex.

Chromosome Mapping↗
PubMed1981

Intra HLA-D region recombinant maps HLA-DR between HLA-B and HLA-D.

A consanguineous family has been typed for HLA-A, B, C, D, DR and GLO, Bf, C2 and C4 and other red cell markers. The results indicate that an expected Dw7 homozygous sibling is a "Dw1"/Dw7 recombinant, probably derived from a crossing over between DR and D on the paternal haplotypes. The anomalous typings by Dw1 HTCs of the recombinant haplotype are best explained by the likely presence of an additional Lad polymorphism which could be a serologically detectable second epitope on the same molecule as the HLA-D determinant or in the form of two linked chains, one encoded by HLA-D and one by another Lad gene in the HLA haplotype.

Blood Grouping and Crossmatching↗
PubMed1981

Sources of variance in the double normalized value: an evaluation of its reproducibility as a measure on HLA-D locus identity.

Two different sets of mixed lymphocyte culture (MLC) experiments were performed using HLA-D homozygous typing cells (HTC). In all stimulator-responder combinations the median cpm's of four replicate cultures were reduced into double normalized values (DNV). In the first experimental set the responder panel was unselected, whereas the responders for the second set were chosen on the basis of either sharing an HLA-D determinant with the stimulator (ID) or not (non-ID). The experiments were designed: Set 1: To estimate the technical variability in the DNV's and to observe the distribution of this variability. The standard deviation of an observation on a stimulator-responder combination was approximately 24 DNV units. Thus, by running 6 experiments on each responder we would have a mean DNV with a standard error of 10 DNV units. Set 2: To determine whether stimulators typing for the same Dw specificity had the same distribution of DNV's and to investigate the variability between responders, between experiments and within experiments. Although the mean DNV is the same for all HTC's, the variability in observations was greater for some HTC's than for others. The variability may be completely technical for some HTC's, whereas for other HTC's there is evidence of responder variability and between experiment variability. Important implications of these results are: (1) that in using a single cut-off value of 60 for all HTC to define typing responses one will have a very high misclassification rate for a large percentage of ID responders; (2) for some HTC this error rate can be reduced through repeating the experiment 4 times and raising the cut-off point; (3) this error, together with the technical and/or experimental variance can be further reduced by using 2 or more HTC's of the same specificity in each experiment and by combing their data; (4) misclassification can be reduced in every situation by doing 4 experiments, using 2 HTC per responder and computing a cut-off which gives a misclassification rate for each Dw type of 10% in ID's and in non-ID's. Thus the best approach to achieving Dw locus typing with a desirable low rate of misclassification would be to do similar control studies of every HTC, to estimate technical experimental and responder variance and then use this information to determine a cut-of value and the number of HTC's and experiments per responder required to keep the error rate at a satisfactory level.

Cells, Cultured↗
PubMed1980

Type 1 diabetes and the HLA-D locus.

HLA-D specificities have been investigated in 58 classical Type 1 diabetics and 43 healthy subjects. Both groups were selected according to the HLA-B locus antigens which are known to have a significant positive or negative association with the disease. The results indicate that (1) the primary association of the disease is with HLA-DW3, (2) the increased frequency of DW4 in diabetics with rare exception is co-existent with the presence of DW3, (3) the low frequency of DW2 is secondary to the increase in DW3 and/or DW4, and is not consistent with a primary 'protective' role. It is suggested that these data support the hypothesis of interaction between HLA-linked genes operating by separate mechanisms to confer the susceptibility to young onset Type 1 diabetes (Type 1 A).

Adolescent↗
PubMed1979

"Ia-like" antigens on human T cells.

Human T lymphocytes have been tested for cell surface p. 28,33 "Ia-like" heteroantigen and DRw alloantigens. Small numbers (1--5%) of sheep (E) rosette or T antigen-positive, surface immunoglobulin-negative (E+, T+, smIg-) T cells were Ia+; these cells appeared to be restricted to the TG subset. Following activation by allogeneic lymphocytes or sperm, or by purified protein derivative of tuberculin (PPD), the proportion of positive T cells increased substantially. DRw typing indicated that Ia specificities on activated T cells were not acquired passively from the stimulator cells, suggesting therefore that either "selection" of a small DRw+ cell subset or derepression and/or exposure of DR locus gene products occurs during T cell activation.

Antigens, Surface↗