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M M Tongio

Publications and source records attributed to M M Tongio.

At least 19 recordsLinked to original sources
PubMed1995

Association of intermediate uveitis with HLA-A28: definition of a new systemic syndrome?

BACKGROUND: Endogenous posterior uveitis (PU) can be associated with systemic diseases, and certain forms have strong association with HLA antigens. Much less is known regarding intermediate uveitis (IU). The purpose of this study was to determine whether IU is associated with the HLA system and whether it can be associated with systemic symptoms. METHODS: In 179 consecutive patients consulting for uveitis, a detailed history was obtained and a physical examination performed. HLA typing for 71 HLA-A, B, DR and DQ antigens, laboratory tests, and radiography of the chest, sinuses, and sacroiliac joints were systematically performed. RESULTS: Thirty-two patients (18%) had IU; 51 (28.5%) had PU and constituted our internal control group. Nine of the patients with IU (28%) had the HLA-A28 antigen, compared with 8.1% of a healthy control population and 8.6% of the patients with PU (P < 0.001). An associated disease was found in four patients with IU (12.5%) (none was HLA-A28) and in 45% of the patients with PU (P < 0.01). Some 67% of HLA-A28 patients with IU had arthralgias affecting the knee(s), compared with 17% of non-HLA-A28 patients and 18% of patients with PU (P < 0.05 and P < 0.01 respectively); 55% had gonalgias and hypocomplementemia compared with 9% and 2% respectively (P < 0.01 and P < 0.001). CONCLUSIONS: IU is significantly associated with HLA-A28; patients having this antigen may represent a subset of the disease characterized by an increased prevalence of arthralgias and hypocomplementemia.

Adolescent↗
PubMed1995

Reevaluation of the relative risk for susceptibility to celiac disease of HLA-DRB1, -DQA1, -DQB1, -DPB1, and -TAP2 alleles in a French population.

In a population of 46 children with CD recruited in the Paris area of France, an excess of DRB1*03 and DRB1*07 alleles and of DR3/DR7, DR3/DR3 and DR11(or 12)/DR7 phenotypes was found (RRs of 6.3, 9.3, 24.6, 15, and 15.1, respectively), which is reminiscent of the markers of susceptibility observed in southern rather than in northern European celiac patients. More importantly, the highest association with CD was not found in individuals expressing the DQA1*0501-DQB1*0201 heterodimer in single dosage (RR = 24.9) or in homozygous state, but in people co-expressing one copy of DQA1*0501-DQB1*0201 on one haplotype and a second copy of DQB1*0201 on the second haplotype (RR = 35.7). This suggests that in our population either DQB1*0201 or a gene closely linked to DQB1*0201 influences the susceptibility to CD conferred by the DQA1*0501-DQB1*0201 heterodimer. Significant positive or negative RRs conferred by some TAP2 or DPB1 alleles were found. However, they were moderate compared to the RR conferred by the expression of a second copy of DQB1*0201. Moreover, they were no longer significant when patients were compared with HLA-DR matched controls. This suggests that associations of CD with TAP2 and DPB1 alleles are secondary to linkage disequilibria and argues against the contribution of these alleles in resistance and/or susceptibility to CD. Thus the "raison d'être" of a "DQB1*0201 second haplotype effect" in susceptibility to CD remains to be elucidated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

CD1 expression is not affected by human peptide transporter deficiency.

Conventional major histocompatibility complex class I molecules are highly polymorphic and present peptides to cytotoxic T cells. These peptides derive from the proteolytic degradation of endogenous proteins in the cytosol and are translocated into the endoplasmic reticulum by a peptide transporter consisting of two transporter associated with antigen processing (TAP) molecules. Absence of this transporter leads to the synthesis of unstable peptide free class I molecules that are weakly expressed on the cell surface. Mouse nonconventional class I molecules (class Ib) may also present TAP-dependent peptides. In humans, CD1 antigens are nonconventional class I molecules. Recently, we characterized a human HLA class I deficiency resulting from a homozygous TAP deficiency. We show here that CD1a and -c are normally expressed on epidermal Langerhans cells of the TAP-deficient patients, as are CD1a, -b, and -c on dendritic cells differentiated in vitro from monocytes. Moreover, the CD1a antigens present on the surface of the dendritic cells are functional, since they internalize by receptor-mediated endocytosis gold-labeled F(ab')2 fragments of an anti-CD1a mAb. This suggests either that CD1 molecules are empty molecules, that they are more stable than empty conventional class I proteins, or that CD1 molecules present TAP-independent peptides.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

[Expression of HLA-DP antigens on normal and leukemic blood cells].

HLA-DP allodeterminant elicit weak cellular and humoral immune responses. This study was undertaken to find out if the low immunogenicity of HLA-DP could be accounted for by a low level of expression on peripheral blood mononuclear cells. Double staining experiments and flow cytometry were performed in 28 healthy individuals, HLA-DP was found to be as expressed as DR and DQ on B lymphocytes. Furthermore, a DP+/DR- lymphocyte sub-population was identified and characterized as freshly activated T lymphocytes.

Adult↗
PubMed1992

Multifactorial analysis of the outcome of 6430 cadaver kidney grafts.

A total of 6430 cadaver kidney grafts performed within the network of France-Transplant between 1 January 1978 and 1 January 1989 were analyzed. Each case was examined comprehensively in regard to 12 variables. A multifactorial analysis (Cox regression) was used to determine the degree of association between each covariate and the outcome of the graft. The results were evaluated by calculating relative risks of graft failure for each variable. A total of seven covariates appeared to influence graft survival significantly: the period of transplantation (P = 10(-8)), retransplantations (P = 0.003), age and sex of the donor (P = 0.003 and 0.009 respectively), duration of pretransplant dialysis (P = 0.03), pretransplant sensitization to HLA antigens (P = 0.05), and matching for HLA-A, -B, and -DR loci (P = 0.03). This last parameter has previously been reported as influencing the outcome of the graft in seven out of eight international studies carried out using similar methodology.

Adolescent↗
PubMed1992

DP epitope mapping by using T-cell clones.

To determine whether a correlation exists between the genomic HLA class II DP DNA polymorphism and cell surface expression and to detect the DP epitopes responsible for alloreactivity, anti-DP T-cell clones were generated against new PLT blank RFLP DPa and DPb-defined specificities. The clones were tested on the 10th IHWS B-LCLs and on local panel cells. Oligotyping of the tested cells made it possible to (a) correlate the DPa specificity with the DPB1*0402 specificity and (b) split DPb into DPB1*1001 and DPB1*1401. By comparing DNA sequences of the second exon to panel reactivity, the epitopes responsible for DPB1*1001 and 1401 were defined and attributed to beta-chain residues contributing to peptide selection inside the HLA groove. However, DNA sequences could not explain anti-DPa allospecificity, indicating that another structure not yet definable may be involved.

Amino Acid Sequence↗
PubMed1992

Complexity of the HLA-DP region: RFLP analysis versus PLT typing and oligotyping.

A total of 84 individuals were DP typed in parallel with the restriction fragment length polymorphism (RFLP) analysis and the primed lymphocyte test (PLT). Whereas 80% of the cases gave concordant results, the other 20% showed discrepancies for one of the two alleles carried by the typed individuals. Oligotyping, PCR-RFLP and sequencing confirmed the results found by PLT. The 20% discordant results obtained with RFLP led us to conclude that RFLP typing cannot replace PLT typing. From a more general point of view, the RFLP analysis revealed the DP region to be more complex than expected since for each given PLT DP defined specificity, more than one RFLP DP haplotype could be determined. These were possibly induced by crossing-overs or gene conversion events.

Alleles↗
PubMed1992

[Analysis of frequency of DR3 allele in rapidly evolutive forms of Crohn disease in adults; comparison with the occurrence of this allele in slowly evolutive forms and in the normal population].

This communication reports 1. the frequency of the DR3 allele among 86 patients exhibiting various evolutive courses of Crohn's disease (CD), diagnosed in the same hospital in Alsace, France, hospitalized at least once between 1964 and 1986 and followed for at least 1 year, 2. the frequency of the DR3 allele among a control population in the same area: 126 volunteers donors of bone marrow. The definition of the evolutive course was similar to the one published by Binder et al.: slow course (including: intermittent: "occurrence of symptom-free period(s) of at least one month's duration excluding period where the patient was in steroid treatment"; and inactive: "completely free of bowel symptoms during the year") as opposed to continuous evolution: "without symptom-free periods". The DR3 allele determination was established by classical serologic analysis. 26 patients were found with the DR3 allele; 14 belonged to the slow course group, 12 to the continuous evolution group; 60 patients did not exhibit the DR3 allele: 50 in the slow course group, 10 in the continuous evolution group. chi 2 = 8.28; p = 0.004. Therefore the frequency of the DR3 allele was very significantly higher in the group with the continuous course (55%) than in the slow course group (22%). Similarly the frequency of the DR3 allele in the group with the continuous course (12/22: 55%) was significantly higher than in the group of control subjects (34/126: 28%) chi 2 = 6.64; p = 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[HLA class II DP antigens and bone marrow transplantation].

The biochemical structure of the HLA class II DP antigens is close to that of the remainder DR and DQ isotypes. Nevertheless, they may play a peculiar functional role. Their importance in bone marrow transplantation, where a complete HLA class II identity between graft donor and recipient is requested, is not yet known. The detection of a DP mismatch by using the mixed lymphocyte reaction is quite difficult. The role of such a mismatch in the incidence of graft versus host disease (GVHD) or graft rejection has to be defined. Studies on large series of recombinant families, using oligotyping, are necessary.

Bone Marrow Transplantation↗
PubMed1991

IgM anti-idiotypes that block anti-HLA antibodies: naturally occurring or immune antibodies?

Using dithiothreitol (DTT) technique, IgM anti-HLA anti-idiotypic antibodies were detected in a multiparous multitransfused woman. These antibodies were able to inhibit the binding of specific IgG anti-HLA antibodies on their corresponding antigen. The recognized determinants were cross-reactive determinants since they were partially found on anti-HLA antibodies from unrelated individuals. By studying the patient's sera over a period of 2 years, no IgM-IgG switch was observed but the presence of these antibodies was stable in time, despite the disappearance of the idiotypes (anti-HLA antibodies). However, when looking at the patient's earlier serum, it was shown that these IgM anti-idiotypic antibodies were absent from the first available serum. Thus, these anti-idiotypic antibodies seem to behave both like natural and immune antibodies. The incidence of such antibodies in pretransplant patients is discussed.

Adult↗
PubMed1990

HLA-DR1 and DRw6 association in DR4-negative rheumatoid arthritis patients.

This study of 110 seropositive rheumatoid arthritis (RA) patients confirms the significant association of susceptibility to RA with HLA-DR4 specificity (P less than 0.001). The DR1 frequency is elevated in the entire seropositive patient group, reaching marginal significance (P less than 0.025). The DR4-negative patients, however, have a much higher prevalence of DR1 (P less than 0.001). Surprisingly, the DRw6 specificity is significantly increased in the remaining DR4- and DR1-negative patients (P less than 0.01). These results demonstrate that RA is not associated with a single HLA-specificity, but to various degrees with DR4, DR1, and DRw6. These findings, and particularly the newly recognized association with DRw6, support the hypothesis that functionally equivalent shared epitopes or conformations on otherwise distinct MHC molecules may confer risk for developing RA.

Arthritis, Rheumatoid↗
PubMed1990

A nucleotide substitution in a Bg1 II site is responsible for the RFLP discrimination between DPw4 and DPa.

In a previous work we showed that the two functionally different specificities DPw4 and DPa could only be differentiated by RFLP analysis using two mutually exclusive fragments (respectively, Bg1 II 5.29 kb for DPw4 and 7.24 kb for DPa). The DP Workshop synthetic analysis localized these fragments in the DPA2 pseudogene region. Our results demonstrate, however, that they are located between the A1 and B1 genes; the Bg1 II restriction site responsible for the 5.29 kb fragment was localized between the first and second exon of the DPB1 gene and inside the 7.24 kb fragment. A single mutation point inside this restriction site is responsible for the absence of the 5.29 kb fragment, changing the specificity attributed by RFLP typing.

Bacterial Proteins↗
PubMed1990

[Post mortem HLA phenotyping of donors of eyes. Evaluation of a serological method of microlymphotoxicity on lymphocytes and PHA lymphoblasts].

To increase the number of HLA typed corneas a microlymphocytotoxicity assay on lymphocytes and PHA lymphoblasts was investigated. A double immunofluorescence technique using magnetic beads coated with anti-T8 (for class I) and anti-DR (for class II) monomorphic antibodies was applied. Blood samples from 50 non selected donors were obtained. HLA class I and class II typing was possible in 74% of the cases. Using PBL's (Peripheral Blood Lymphocytes) HLA class I could be defined in 29 out of 50 Cases and class II in 15 out of 50 cases. On PHA blasts HLA class I and class II antigens could be defined in 32 and 33 out of 50 cases respectively. Mean time of culture was 10 days (6-20). No influence of donor age and post partum time could be observed. By combination of both methods a significant proportion of eye donors could be reliably typed within a short time.

Adult↗
PubMed1989

Multiple sclerosis, sleep latencies and HLA antigens.

The role of HLA antigens, and HLA-DR2 in particular, in the determination of mean sleep onset latencies (MSOLs) in multiple sclerosis (MS) was studied. It has been suggested that this antigen may play a part in the reduction of MSOLs, since nearly 100% of patients suffering from narcolepsy are DR2-positive. A multiple sleep latency test was performed in 37 patients suffering from MS without spontaneous complaints of sleep disturbances and who were typed for HLA-A, B, C, DR and DQ. The MSOL was reduced in a total of 21 patients, in only 7 of 15 DR2-positive patients and in 12 of 21 DQw1-positive patients. However, it was reduced in 13 of 16 B8- or B14-positive patients. In contrast with this, in the absence of an early sleep onset (MSOL greater than 30 min), no HLA antigens were found to be over-represented when considered individually; only those patients positive for a group of cross-reacting HLA antigens (B5, B15, B18, B21 or B35) had an MSOL greater than 30 min. These results suggest that the genes which code for the DR2 or DQw1 antigens, which are present in nearly 100% of narcoleptics, are not solely responsible for the appearance of an early sleep onset in MS.

Adult↗
PubMed1989

A T-cell clone recognizing an MLC stimulating epitope located on the DRw11 beta 1 chain.

An alloreactive proliferative T-cell clone, 6065 WS, was obtained in an intrafamilial cell combination where the stimulator was a homozygous DRw11, DRw52, DQw3 son and the responder his haploidentical mother. Proliferation assays on eight local DRw11 families, 75 homozygous B-cell lines (Tenth Histocompatibility Workshop panel) and blocking assays with monoclonal antibodies showed that clone 6065 WS recognizes an epitope on the DRw11 beta 1 chain. Comparison of the reactivity of clone 6065 WS with cells expressing the three known DRw11 beta 1 amino acid sequences identified two unique amino acids at positions 71 and 86 which contribute to determining the specific recognition by the T-cell clone 6065 WS. Our data suggest that one or both of these amino acids can either be directly involved in the recognition by the T-cell receptor or responsible for critical conformation of the determinants on the DR molecule. Alternatively, they could affect recognition of a self peptide bound to the major histocompatibility complex class II molecule.

Amino Acid Sequence↗
PubMed1989

Molecular basis of complete C4 deficiency. A study of three patients.

The highly polymorphic fourth component of human complement (C4) is usually encoded by two genes, C4A and C4B, adjacent to the 21-hydroxylase (21-OH) genes and is also remarkable by the high frequency of the null alleles, C4A*Q0 and C4B*Q0. Complete C4 deficiency is exceptional because this condition appears only in homozygotes for the very rare double-null haplotype C4AQ0,BQ0. This condition in most cases gives rise to systemic lupus erythematosus and an increased susceptibility to infections. The molecular basis for complete C4 deficiency has not yet been established. Therefore we studied the DNA of three previously described C4 deficient patients belonging to unrelated families by restriction fragment length polymorphism analysis using C4 and 21-OH probes. These studies revealed a deletion of the C4B and 21-OHA genes in two patients and no deletion at all in the third patient. Therefore, complete C4 deficiency as a result of homozygosity for the C4AQ0, BQ0 haplotype is not a consequence of a deletion of the C4 genes. The molecular basis of this genetic abnormality is certainly very complex and may vary also from one case to another.

Alleles↗