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N Simonney

Publications and source records attributed to N Simonney.

16 recordsLinked to original sources

[Advantages and drawbacks of in vitro Interferon-gamma/T cell assays compared to the Mantoux test for the diagnosis of tuberculosis].

The development of in vitro blood tests that measure the delayed hypersensitivity reaction developed after contact with Mycobacterium tuberculosis will change progressively the diagnosis of M. tuberculosis infection. These blood assays (Quantiferon TB Gold, Cellestis, Australia; T-SPOT.TB, Oxford Immunotec, United Kingdom) use specific, complex M. tuberculosis antigens (ESAT-6 and CFP-10), whereas the intra-dermal Mantoux test is done with tuberculin, a complex mixture of more than 200 antigens. ESAT-6 and CFP-10 are absent from all the BCG vaccine strains used throughout the world. Significant improvement in the specificity with equivalent or increased sensitivity of the in vitro tests compared to the Mantoux test will lead eventually to replacement of the latter.

Diagnosis, Differential↗

Kinetics of circulating antibodies, immune complex and specific antibody-secreting cells in tuberculosis patients during 6 months of antimicrobial therapy.

OBJECTIVE: During the follow-up of a group of patients with active tuberculosis, the predictive potential of several antibody-based assays was evaluated in monitoring treatment efficacy. DESIGN: Eleven patients with bacteriologically documented pulmonary tuberculosis and two patients with tuberculosis pleurisy were studied over a period of 6 months, from the day before treatment to its completion. The kinetics of the humoral response to Mycobacterium tuberculosis was determined by the number of specific circulating antibody secreting cells (ASC) (ELISPOT assay), as well as the titres of specific circulating antibody and specific antibody present in circulating immune complexes (quantitative ELISA). RESULTS: Follow-up ELISPOT assays, performed after initiation of tuberculosis therapy showed a rapid increase of ASC, during the first week, followed by rapid 3-10 fold decline of ASC in 12 of 13 patients tested. This decline occurred more rapidly than the mycobacterial culture conversion. In contrast, follow-up of ELISA assays did not give relevant information in assessing the outcome of treatment. CONCLUSION: In comparison with direct detection of tubercle bacilli in sputum samples, the rapid clearance of specific circulating ASC occurring early on after the onset of therapy could suggest a potential usefulness of ELISPOT in monitoring therapeutic response.

Adult↗

Analysis of circulating immune complexes (CICs) in childhood tuberculosis: levels of specific antibodies to glycolipid antigens and relationship with serum antibodies.

BACKGROUND: The presence of specific antiglycolipid antibodies in serum and circulating immune complexes (CIC) in children with tuberculosis was detected in order to evaluate their contribution to the value of serodiagnosis of tuberculosis, as has already been shown in adults. METHODS: ELISAs using the three glycolipids LOS, DAT and PGLTb1 were performed in whole serum and immune complexes from 20 children with tuberculous disease or infection, in seven child contacts, and in 26 children with non-tuberculous disease. The contribution of complexed IgG antibody to the diagnostic values was established for each group. RESULTS: The antibody levels in free serum were higher (P < 0.01) in children with tuberculous disease or infection and in contacts than in controls. By contrast, except for PGLTb1, the IgG antibody levels were higher (P < 0.02) in children with tuberculous disease than in the other groups. The highest contribution of IgG antibody against LOS to the predictive values was shown in children with pulmonary tuberculosis (positive predictive value 1,000, negative predictive value 1,000). In paucibacillary tuberculosis (extra-pulmonary and tuberculous infection) and in contacts, the IgG antibody did not contribute to the sensitivity of the serodiagnosis, where the combination of antigens tested in serum increased the diagnostic yield. The very low levels of IgG antibody in these settings may indicate a different B cell response. CONCLUSION: The detection of immune complexes and IgG antibodies against the three glycolipid antigens is useful as a complementary technique for the serodiagnosis of children with a high probability of pulmonary tuberculosis.

Adolescent↗

Circulating immune complexes in human tuberculosis sera: demonstration of specific antibodies against Mycobacterium tuberculosis glycolipid (DAT, PGLTb1, LOS) antigens in isolated circulating immune complexes.

An enzyme-linked immunosorbent assay (ELISA) for IgG using three glycolipid antigens from Mycobacterium tuberculosis in 65 tuberculosis (TB) patients and 50 healthy control subjects was performed. The circulating immune complexes (CICs) were isolated by precipitation with polyethylene glycol 6000 (PEG). This method associated to ELISA measured the specific antibodies present in these CICs. PEG [optical density (OD) 280] was shown to be significantly elevated (P < 0.001) in tuberculous samples. The concentrations of IgG antibodies complexed to the three glycolipid antigens were shown to be higher in patient with tuberculosis than in normal control subjects (P < 0.001). No correlation was observed between levels of free and CIC-bound antibodies. These antibodies isolated from CICs were responsible for almost all of the false-negative serological results. However, great heterogeneity was noticed depending on the antigen used, showing a more positive ELISAs against DAT (77%) than against LOS (71%) or PGLTb1 (18.5%). No correlation was established between the presence of specific CIC-complexed IgG and the bacteriological load or the tuberculosis localization (pulmonary vs. extrapulmonary). The sensitivity of ELISA for CIC-complexed IgG to DAT and LOS was lower in HIV-infected TB patients. From these results, we conclude that detection of complexed IgG DAT and LOS glycolipid antigen will be useful as a complementary technique for the serodiagnosis of tuberculosis.

Adult↗

Recycling of ELISA plates for the serological diagnosis of tuberculosis using a Mycobacterium tuberculosis-specific glycolipid antigen.

A Mycobacterium tuberculosis-specific glycolipid antigen (diacyl-trehalose-DAT) and a battery of defined sera from tuberculous patients were used to evaluate the reliability of recycling ELISA microplates for serodiagnosis of tuberculosis. The reuse of plates was evaluated by the same ELISA technique before and after recycling with an acid buffer to dissociate and release antibodies from antigen-antibody complexes fixed on used plates. The correlation coefficients for comparisons between several new plates used on different days were always higher than r = 0.90, and the variation between tests was always lower than 12%. For comparisons performed systematically between new plates and recycled plates, the values were variable. Up to the fifth recycling, the correlation coefficient was higher than r = 0.60. From the sixth recycling, correlation coefficient values fell to r = 0.381. The results obtained with recycled plates washed manually were much poorer than those obtained after automatic washing. The results described in this report demonstrate that an ELISA test can be performed on recycled plates under the conditions described.

Enzyme-Linked Immunosorbent Assay↗

Analysis of the immunological humoral response to Mycobacterium tuberculosis glycolipid antigens (DAT, PGLTb1) for diagnosis of tuberculosis in HIV-seropositive and -seronegative patients.

Using an enzyme immunoassay (EIA) test, the concentrations of IgG antibodies against 2,3 diacyl trehalose (DAT) and phenolic glycolipid Tb1 (PGLTb1) were measured in the sera of 153 patients with active tuberculosis, 50 of whom were coinfected with HIV, and in the sera of 152 healthy blood donors, 149 asymptomatic HIV-seropositive patients, 12 HIV-seronegative patients with conditions simulating tuberculosis, 23 HIV-seropositive patients with disseminated infection caused by mycobacteria other than tuberculosis and 24 HIV-seropositive patients with pulmonary disease from whom mycobacteria was not isolated in culture. A slightly lower percentage (74%) of the HIV-seropositive than the HIV-seronegative (77%) tuberculosis patients were positive for anti-DAT and anti-PGLTb1 IgG antibodies, with a specificity ranging from 91 to 95%. There was no significant difference between EIA sensitivity in smear-positive and smear-negative patients with pulmonary tuberculosis for all HIV immune statuses and sites of disease (pulmonary vs. extrapulmonary). In HIV-seropositive patients, however, sensitivity was always lower for disseminated tuberculosis than for localized tuberculosis. Combining data for both the smear test and the EIA maximized sensitivity. The main value of the EIA test could be to provide early complementary information by antibody detection in patients with tuberculosis, particularly those with a negative smear test.

Adult↗

Extensive study of DRB, DQA, and DQB gene polymorphism in 23 DR2-positive, insulin-dependent diabetes mellitus patients.

To gain insight into the HLA subregions involved in protection against insulin-dependent diabetes mellitus (IDDM) we investigated the polymorphism of HLA-DR and -DQ genes in 23 DR2 IDDM patients. Results show the following. (1) Fourteen patients (61%) possess the DRB1, DRB5, and DQB1 alleles found in DRw16/DQw5 healthy people. These data contrast with the 5% of DRw16 normally found in DR2 populations and are in agreement with former observations supporting that the DRw16 haplotype is not protective. (2) Nine DR2 patients, i.e., 39% versus 95% in published DR2 controls, possess the DRB alleles found in DRw15 unaffected people. Among them, six patients have also DQA1 and DQB1 alleles identical to those found in DRw15/DQw6 healthy individuals. These data confirm that the DRw15/DQw6 haplotype is protective but indicate that none of the DR or DQ alleles, alone or in association, confers an absolute protection. (3) Our most striking results concern the very high frequency of recombinant haplotypes among the DRw15 patients: 3 of 9. In these three patients recombinations led to the elimination of both DQB1 and DQA1 alleles usually associated with DRw15. This strongly suggests that the occurrence of IDDM in these DRw15 patients is due to the absence of the usual DQ product and thus reinforces the assumption that DQ rather than DR region is involved in the protection conferred by the DRw15/DQw6 haplotype. Finally, analysis of the non-DRw15 haplotypes in heterozygous patients showed that IDDM can occur in the absence of any DQ alpha beta heterodimer of susceptibility.

DNA Probes, HLA↗

[Immunization against the ZWa (PLA1) platelet antigen: group at risk, prevention of complications. Apropos of 132 cases].

The identification of anti-ZWa (-PLA1) alloimmunisation is not very frequent. It can be observed in most perinatal alloimmune thrombocytopenias (PAT) and rare post transfusional purpuras (PTP). On the other hand, the clinical consequences of these immunisations are often dramatic, particularly for the foetuses for which there has been no prevention so far. The retrospective study of 132 cases, 123 PAT and 9 PTP, shows the possible irreversible complications for 18% of the newborns with PAT, but especially for 10% of the foetuses which will show PAT at birth. HLA markers are very useful to detect the people who are likely to develop an anti-PLA1 immunization for they are PLA1 negative and HLA DR3. Then, it becomes possible to prevent the complications of these immunisations. It is what we tried to do through the diagnosis and the treatment of PAT in 3 foetuses.

Antigens, Human Platelet↗

[Neonatal alloimmune thrombopenia].

88 families in which 84 cases of neonatal alloimmune thrombocytopenia (NAT) occurred, were studied. In 84 families, the NAT was the consequence of an incompatibility in the PLA system. Furthermore, the phenotype HLA-DR3 increases greatly the risk of immunisation (RR: 76,5). The importance of the risk of neurological sequellae was shown by the clinical study (about 25% of the surviving neonates). The occurrence of the accident at the first birth of a PLA1 positive child in a sibship was frequent (59%). In addition, the NAT recurred at each birth of a PLA1 positive child with only five exceptions. All of them concern a female neonate and this might be meaningful. Therapeutical data are heterogeneous and difficult to interpret. However, it appears that the prevention of obstetrical traumatism by caesarean section and compatible platelet transfusions are useful. It is too early to evaluate the efficacy of prenatal transfusions of mother's washed platelets. However, in the two cases in which we use them, they gave a good and sustained platelet count increment. The prenatal diagnosis of NAT and the PLA grouping of the foetus has been proposed in three cases and are feasible at 20 weeks of pregnancy.

Blood Platelets↗

HLA antigens in hemophiliacs A with or without factor VIII antibodies in a Venezuelan Mestizo population.

Twenty-eight unrelated hemophilia A patients, seven of them with anti-factor VIII antibodies were typed for HLA-A, B, C antigens and 25 of them for HLA-DR. The results show a significant difference in HLA-DR4 frequency between hemophiliacs with antibodies who lack this antigen and hemophiliacs without antibodies, in whom HLA-DR4 is increased as compared to a healthy control series. This data suggests that DR4 may be associated with a factor preventing anti-factor VIII immunization.

Antibodies↗

Cytotoxic antibodies in sera of Venezuelan multiparous women of Amerindian and mixed ethnic origin.

Sera from 464 multiparous women of mixed ethnic origin and 114 Amerindian mothers (Warao of Western Venezuela), were studied for lymphocytotoxicity using a panel of B and T lymphocytes isolated from 50 to 100 individuals from the same populations. Twenty-five and 9.65% of the sera, respectively, showed activity against at least 5% of the panel. Among the women of mixed ethnic origin 10% produced antibodies directed against one or more HLA Class I antigens while 2 sera contained monospecific anti-DR antibodies; among the Warao, only 2 sera recognized HLA antigens: a Bw51 and an undetermined Cw antigen which shows linkage disequilibrium with Bw16 in both populations.

Adult↗

HLA-D typing with homozygous cells identified in an American indigenous isolate. II. Family studies and D/DR relationship.

Twelve American Indian nuclear families with 2-5 siblings have been HLA-D typed using mixed lymphocyte cultures and clusters of homozygous typing cells (HTC) of Caucasoid origin to detect DW1-DW7 and typing cells of American Indian origin to detect LD5A, LD15A and LD15B antigens. Results obtained demonstrate complete absence of DW1-DW7 in these families and illustrate the inheritance and segregation of LD5A, LD15A and LD15B. DR typing results obtained with the 8th International Histocompatibility Workshop genetic set of antisera indicate inheritance in coupling of DR2 with LD5A, of DR6.2 (DR3+6, MT1 negative, MT2 positive) with LD15A, and of DRW8 with LD15B. The existence of MLC activating antigen(s) different to DW4, yet associated to DRW4 in this population is postulated. The D/DR relationship present in this American Indian isolate demonstrate once more that DR2 can be inherited in combination with an HLA-D antigen different to DW2, and that LD15A HTC define a second sub-cluster of the broad DW6 specificity group, which is inherited with DRW6.2 and BW62 antigens in the Warao population.

Family↗