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R J Duquesnoy

Publications and source records attributed to R J Duquesnoy.

At least 37 records · Page 2Linked to original sources
PubMed1994

Progress report on the ASHI/CAP Proficiency Survey Program in Histocompatibility Testing. I. HLA-A,B,C typing, antibody screening, and lymphocytotoxicity crossmatching. American Society for Histocompatibility and Immunogenetics. College of American Pathologists.

The Histocompatibility Survey Program was organized in 1982 as a joint project by the ASHI and CAP to evaluate laboratory performance in HLA typing, lymphocytotoxicity crossmatching, and antibody analysis. This report summarizes the experience with the HS surveys on HLA class I serology. During a 12-year period, the number of participating laboratories increased from 150 to 285 and HLA typing was done with 90 survey specimens representing 20 HLA-A and 35 HLA-B antigens. Most unsplit antigens were correctly identified in more than 90% of the laboratories. For many antigens, a high percentage of participants reported a split and there was generally a high consensus of a correct assignment. Nevertheless, several antigens were difficult to define, as shown by low consensus rates. During recent years, the assignments of Bw4/6 and HLA-C antigens have significantly improved. Lymphocytotoxicity crossmatching was analyzed for 138 cell-serum combinations tested by an average of 143 laboratories. Comparisons between four techniques (basic NIH, Amos modified, LI, and AHG) showed consistent results (greater than 90% crossmatch compatibility or incompatibility) for 71% of the cell-serum combinations. The crossmatch results with the remaining combinations were more variable for one or more of the crossmatch techniques. Serum antibody identification showed a continued improvement during recent years, and the average consensus for assigning acceptable antibody specificity reached 88%. A performance grading system based on a 90% consensus rate among participants is used to satisfy requirements for laboratory accreditation.

Cytotoxicity Tests, Immunologic↗
PubMed1994

Progress report on the ASHI/CAP Proficiency Survey Program in Histocompatibility Testing. II. HLA-DR, DQ serologic typing, antibody identification, and B-cell crossmatching. American Society for Histocompatibility of Immunogenetics. College of American Pathologists.

This report summarizes the 8-year experience of the DR survey program designed to evaluate the performance of histocompatibility laboratories in the serologic typing of cell specimens for HLA-DR and HLA-DQ polymorphisms and the HLA class II antibody identification and B-cell crossmatching of serum specimens. The number of participants increased from 45 in 1985 to 214 in 1992. Although the performance criteria are based on laboratory consensus, the availability of DNA typing since 1990 has enabled a critical assessment of the reliability of serologic HLA-DR, DQ typing. The survey results shows that unsplit HLA class II antigens DR1-DR8, DR52/53, and DQ1-3 are generally correctly identified in over 90% of the participating laboratories. DR9 and DR10 have not yet been tested and testing for DQ4 has not yet achieved this level on consensus. In contrast, the assignments of serologic subtypes of HLA-DR and HLA-DQ are less consistent and frequently unreliable. Although the B-cell crossmatches show generally high laboratory consensus rates, the serum screening results show frequently inconsistent results regarding HLA class-II-specific antibody identification.

Antibody Specificity↗
PubMed1994

Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies.

Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (> 10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although performed lymphocytotoxic antibodies are not an absolute contraindication to combined liver-kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed.

Adolescent↗
PubMed1993

The influence of HLA matching on cytomegalovirus hepatitis and chronic rejection after liver transplantation.

Previous findings in liver transplantation patients have raised the concept that HLA plays a dualistic role. HLA matching will reduce rejection but may augment MHC restricted cellular immune mechanisms of liver allograft injury. To evaluate this concept, we studied CMV hepatitis in 399 FK506-treated liver transplant patients, including 355 cases for which complete HLA-A,B,DR,DQ typing information was available. CMV hepatitis developed in 25 patients, and 17 of them (or 68%) showed a one or two HLA-DR antigen match with the donor. In contrast, HLA-DR matches were found in only 35% of 330 patients without CMV hepatitis (P = 0.005). No significant associations were seen for HLA-A, HLA-B, and HLA-DQ antigens. In pretransplant CMV-seronegative patients with seropositive grafts (n = 39), the frequency of CMV hepatitis was 44% for HLA-DR-matched livers but 14% for HLA-DR-unmatched livers. In seropositive recipients (n = 187), these frequencies were 12% and 2% for HLA-DR-matched and unmatched liver grafts. Chronic rejection developed in 29 patients (or 8%) during a follow-up between 10 and 24 months after transplantation. Its incidence was higher in the CMV hepatitis group (24% vs. 6%) (P = 0.007). Although no associations were found between HLA matching and the incidence of chronic rejection, there was an earlier onset of chronic rejection of HLA-DR-matched livers irrespective of CMV hepatitis. These findings suggest that an HLA-DR match between donor and recipient increases the incidence of CMV hepatitis in both primary and secondary CMV infections. Although HLA compatibility leads to less acute cellular rejection, it is suggested that DR matching may accelerate chronic rejection of liver transplants, perhaps through HLA-DR-restricted immunological mechanisms toward viral antigens, including CMV.

Chronic Disease↗
PubMed1992

Serum autoantibody to the nucleolar antigen PM-Scl. Clinical and immunogenetic associations.

OBJECTIVE: The inflammatory myopathies are characterized by distinctive autoantibodies that are associated with certain clinical features and immunogenetic patterns. Anti-PM-Scl is one such antibody and is found in pure myositis, myositis in overlap, and systemic sclerosis (SSc). Our purpose was to describe the clinical and immunogenetic associations of the anti-PM-Scl antibody. METHODS: Serum samples from 617 patients with various connective tissue diseases were screened for anti-PM-Scl antibody by indirect immunofluorescence and Ouchterlony double immunodiffusion. Patients with anti-PM-Scl were serologically typed for HLA-DR and DQ, and the genes encoding DQ alpha and DQ beta were characterized by hybridization of sequence-specific oligonucleotide to amplified genomic DNA. RESULTS: Twenty-three patients (4%) had serum anti-PM-Scl. Sixteen had either pure myositis or myositis in overlap, 6 had SSc alone, and 1 had SSc and rheumatoid arthritis. Twenty of the antibody-positive patients had serologic HLA typing performed; 15 (75%) were HLA-DR3 positive, and 17 (85%) expressed the DQw2 allele. None of the 5 DR3 negative patients shared a unique DR or DQ antigen with the DR3 positive patients, and further DNA analysis of 10 patients (4 of whom were DR3 negative) did not reveal any unique DQ alleles. CONCLUSION: Anti-PM-Scl identifies a subset of patients with myositis, SSc, or an overlap of the two disorders, and this antibody has a strong but not exclusive immunogenetic association with the HLA-DR3 antigen.

Adolescent↗
PubMed1992

Mitogen responses of lymphocytes from lung transplant recipients--correlation with rejection and infection.

Proliferative responses to nonspecific mitogens were analyzed for 119 bronchoalveolar lavages and 108 concurrent peripheral blood samples from 35 lung transplant patients. The patients were classified at each time as normal, rejecting, or infected on the basis of trans-bronchial biopsy, culture results, clinical signs, and pulmonary function. During rejection episodes the bronchoalveolar lavage responses to concanavalin A and phytohemagglutinin were significantly increased (P less than 0.004 and P less than 0.006, respectively). The differences were less pronounced when rejection occurred within 30 days after bolus immunosuppressive therapy, either as immunoprophylaxis or as treatment for a previous rejection episode, and were not significantly different from normal. Differences in response during rejection were limited to the graft; analysis of circulating T cells was not helpful (P = NS). In contrast, markedly depressed responses to Con A and PHA were seen during infection. Significant differences were observed both in the graft (P less than 0.007) and in circulating lymphocytes (P less than 0.02), suggesting that global depression of mitogen response is associated with immunocompromise. Sequential analysis of 6 patients showed that individual changes in mitogen response paralleled those seen in the population (P less than 0.046, normal vs. rejection and P less than 0.043 normal). These findings suggest that mitogen assays of bronchoalveolar lavage lymphocytes and, to a lesser extent, PBL, are clinically useful in assessing intragraft immunocompetence and in distinguishing rejection from infection in lung transplant patients.

Bronchoalveolar Lavage Fluid↗
PubMed1992

Genetic, immunological, and metabolic determinants of risk for type 1 diabetes mellitus in families.

Prospective studies of the relatives of people with Type 1 diabetes can provide insights into risk factors for processes leading to the ultimate destruction of the pancreatic islet B-cells. Relatives ascertained through the Children's Hospital of Pittsburgh diabetes registry were followed and rates of conversion to diabetes were determined. We studied the role of genetic and immunological markers, and used the oral glucose tolerance test (OGTT) to study metabolic disturbances among first-degree relatives. A group of siblings was serotyped for the HLA-A and -B antigens, and the degree of HLA haplotype sharing with the diabetic sibling was established. Later, islet cell antibody (ICA) assays were performed, and subjects were followed to determine the predictive value of ICA testing for the subsequent development of diabetes. The rate of conversion to diabetes among the siblings was 14 times greater than the rate observed in the general population from which they come. This is comparable to rates observed by other centres following relatives of people with Type 1 diabetes. Impaired glucose tolerance (by National Diabetes Data Group (USA) criteria) carried a three-fold greater risk for subsequent Type 1 diabetes than did a normal OGTT. Those relatives with detectable ICA were about 50 times more likely to convert to diabetes than were those without ICA. In a group of siblings in whom HLA haplotype sharing was determined, the prevalence of detectable ICA was greater among those who were HLA-identical to the diabetic sibling (9.9%) than among those who were haplo-identical (5.3%) or completely dissimilar (2.4%) at the HLA-A and -B regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Intravenous gamma globulin decreases platelet-associated IgG and improves transfusion responses in platelet refractory states.

In an attempt to improve platelet transfusion responses, intravenous immunoglobulin (IV-IgG) was administered to 19 patients who were refractory to random and best available HLA-matched platelets. A response to IV-IgG was defined as two or more successive transfusions of HLA-matched products that provided recoveries greater than 30%. Thirteen of 19 (68%) patients responded to therapy at a median time of 7 days after initiation of IV-IgG (range = 2-17). Baseline platelet associated IgG levels (PalgG) were elevated in both the responders (61.6 +/- 76.2) (mean +/- SD) and the non-responders (47.0 +/- 46.3 fg/plt). Post-therapy, PalgG levels remained unchanged in the nonresponders but were decreased significantly (p = 0.05) to 11.1 +/- 6.2 fg/plt in the responders. The latter levels were similar to those (11.6 +/- 8.2 fg/plt) measured in a series of 36 transfusion responsive patients. This apparent decline in PalgG was not explained by differences in lymphocytotoxic antibodies (LCT-Ab) after therapy. Moreover, a high degree of alloimmunization was associated with a poorer response to IgG. Only two of eight patients with LCT panel-reactive antibody (PRA) of greater than 85% were responders. By contrast, improved transfusion outcomes were seen uniformly in patients with PRA greater than or equal to 85%. Improved recoveries were obtained using LCT-Ab compatible but not incompatible platelets. The median increment (% predicted) with compatible platelets before therapy was 6.0 +/- 9.9 (SD). Post-IgG, median recoveries were 37.0 +/- 31.2 percent, P less than 0.001. These findings suggest that IV-IgG may alter destructive mechanisms that affect the survival of compatible platelets in refractory patients.

Antibodies↗
PubMed1991

The immunosuppressive activity of the aldehydic transformation of cyclosporine on alloreactive T-cells.

Cyclosporine (CsA) is a potent immunosuppressive compound, and its metabolites have previously been shown to have pharmacologic activity. The aldehydic metabolites have been isolated and are a metabolic intermediate after the conversion of CsA to its most active hydroxylated metabolite. The in vitro sensitivity of alloreactive T-lymphocytes, which are generated from a mixed lymphocyte reaction and propagated from organ transplant biopsy specimens to the aldehydic metabolites of CsA, was tested. In secondary proliferative assays in the presence of varying concentrations of CsA and the aldehydes, the concentration required to inhibit proliferation by 50% was 50 to 150 ng/mL for CsA and 3150 to 3500 ng/mL for the aldehydes. Pretreatment of alloreactive cells with CsA or the aldehydes did not alter cell viability, as tested with dye exclusion, or cell reactivity on reculturing. These studies concluded that the structural modification formed by metabolism of CsA to the aldehydic structure eliminates its antiproliferative activity on T-lymphocytes.

Aldehydes↗
PubMed1991

Cytomegalovirus serologic status and postoperative infection correlated with risk of developing chronic rejection after pulmonary transplantation.

Twenty-seven patients received pulmonary transplants during the period since we began routine use of cytomegalovirus-seronegative blood products for CMV-seronegative recipients. Preoperative serologic status of the recipient and the occurrence of cytomegalovirus infection in the postoperative period were correlated with development of obliterative bronchiolitis (OB) as diagnosed by transbronchial biopsy (TBB). Patients included 20 heart-lung and 7 double-lung recipients. OB occurred in 18 of 27 patients. All 3 CMV seronegative recipients receiving lungs from a seropositive donor and 9 of 10 CMV recipients seropositive at the time of transplantation developed OB compared with only 6 of 14 CMV seronegative patients receiving seronegative grafts (P = 0.018). CMV infection occurred in 10/27 patients, of whom 5 were asymptomatic; 90% of these patients developed OB. Donor-specific alloreactivity, based on primed lymphocyte testing (PLT) of bronchoalveolar lavage cells was found at the time of diagnosis of OB in 23 of 27 patients. A positive PLT was significantly associated with the presence of OB (P = 0.017). We conclude that preoperative seropositive status for CMV, grafting of organs from seropositive donors, and postoperative CMV infection are significant risk factors for developing OB. That OB is, in part, an immunologically mediated form of injury and represents chronic rejection is supported by the presence of donor-specific alloreactivity in BAL lymphocytes from all recipients with OB.

Antibodies, Viral↗
PubMed1991

Histocompatibility and other risk factors for histological rejection of human cardiac allografts during the first three months following transplantation.

A histological analysis of 2564 endomyocardial biopsies was conducted in 349 cardiac transplant patients to determine potential risk factors for acute cellular rejection during the first three months following transplantation. This analysis dealt with the frequency, time of onset, and duration of cellular rejection. Patients on perioperative RATG experienced significantly less rejection than patients on OKT3 or without antilymphocyte antibody immunoprophylaxis. A trend was noted toward increased rejection in recipients diagnosed originally with chronic myocarditis compared with patients in other disease categories including ischemic heart disease and dilated cardiomyopathy. No significant differences were seen in histological rejection between male and female recipients. On the other hand, patients over 55 years of age were found at lower risk of histological rejection. The results of this analysis have demonstrated quite clearly, but not unexpectedly, that a greater degree of HLA mismatching correlates with increased cellular rejection. This effect was noted not only for the HLA-A,B and DR antigens, but also HLA-DQ and HLA-DRw52/53 antigens. In multivariate analysis, the highest level of statistical significance was obtained for the combined HLA-A,B,DR and DQ group. Sensitized patients with panel-reactive lymphocytotoxic antibodies of greater than 10% experienced more histological rejection than nonsensitized patients. On the other hand, a positive lymphocytotoxic crossmatch did not appear to influence cellular rejection of cardiac allografts. Also, no differences were seen in histological rejection between ABO-identical and compatible heart transplants. These findings further support the concept that donor HLA compatibility and pretransplant sensitization represent significant risk factors for cellular rejection in cardiac transplantation.

Adolescent↗