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R J Mahoney

Publications and source records attributed to R J Mahoney.

17 recordsLinked to original sources
PubMed2000

HLA-DMA allele polymorphism: no impact on kidney allograft outcome.

The purpose of this study was to analyze the association of HLA-DMA alleles with rejection episodes and early graft loss (EGL) in renal transplant recipients. One hundred and eighty four HLA-DMA alleles were retrospectively analyzed by DNA sequence analysis in 92 kidney transplant recipients. The gene frequencies of HLA-DMA *0101, *0102, *0103 and *0104 were found to be similar in all recipients, regardless of rejection vs non rejection episodes and EGL incidence. In conclusion, HLA-DMA allele polymorphism did not impact renal allograft outcome.

Alleles↗
PubMed1999

Inhibition of HLA antibody cytotoxicity by intravenous immunoglobulin G F(ab')2 dimers, monomers, and monovalent F(ab).

IVIgG preparations are clinically relevant to sensitized transplant candidates because they inhibit HLA alloantibody in vitro and in vivo. We hypothesized that IVIgG F(ab')2 idiotypic-antiidiotypic dimers may possess a greater immunomodulatory capacity when remonomerized than non-dimerizable F(ab')2 monomers in IVIgG. We reasoned that when 60-75% of potential antiidiotypic IVIgG monomers fail to bind to IVIgG molecules in a large pool of plasma donors (>10,000), IVIgG monomers may fail to inhibit HLA idiotypic antibodies of sensitized transplant candidates. In the first series of AHG T cell crossmatches, non-fractionated IVIgG F(ab')2 was found to inhibit titered HLA antibodies in 13 out of 29 (45%) crossmatch combinations. Crossmatch inhibition was incomplete, i.e., a particular titered HLA antibody specificity was not always inhibited by IVIgG F(ab')2 in every HLA antigen-matched target cell crossmatch. Next, the IVIgG F(ab')2 product was fractionated into F(ab')2 dimers, F(ab')2 monomers and Fab monovalent components by size exclusion high pressure liquid chromatography (HPLC) and retested in crossmatches which previously demonstrated inhibition. The percent of crossmatches that were inhibited by HPLC F(ab')2 IVIgG fractions in three separate experiments was statistically similar for pH 4.0 remonomerized dimers, 82%; pH 6.0 dimers, 50%; monomers, 64%; and monovalent Fab, 64% (p = 0.50). Soluble class I HLA antigen was undetectable in IVIgG F(ab')2 by an ELISA assay. In conclusion, IVIgG dimers and monomers appear to have similar immunomodulatory capacities, and separation of whole IVIgG products into dimer and monomer fractions does not appear to be warranted. Further, IVIgG products should be tested for optimal HLA antibody inhibition in vitro prior to in vivo therapy.

Antibodies, Anti-Idiotypic↗
PubMed1996

Identification of high- and low-risk second kidney grafts.

The purpose of this study was to identify recipients who are at low or high risk of early cadaveric regraft failure by segregating results of the flow cytometric crossmatch (FCXM) test with previous graft survival time (PGST). Early immunologic kidney regraft failure was analyzed in 103 multicenter recipients by cross-stratifying FCXM negative/positive status with < or =3- and >3-month PGST. T cell and B cell cytotoxicity crossmatches were negative. All were tested retrospectively in the T cell FCXM and 60 of the 103 were also tested in the B cell FCXM. A positive T and B cell FCXM was defined as a mean channel shift of > or = 9 (256 channel log scale) or > or = 40 (1024 channel log scale) for pretransplant crossmatch serum above negative control serum. Recipients received triple immunosuppression therapy and limited-use antilymphocyte induction therapy. Early cadaveric regraft losses were biopsied. Comparably good rates of second kidney graft survival at 3 years were found among three ow risk subsets: 78% for 18 FCXM-positive patients with PGST >3 months, 78% for 49 FCXM-negative patients with PGST >3 months, and 84% for 19 FCXM-negative patients with PGST < or =3 months. in contrast, 53% 3-month and 44% 3-year regraft survival rates occurred in 17 high-risk FCXM-positive recipients with a PGST < or =3 months. The odds ratio for increased relative risk of early second graft loss was 4.5 (confidence interval: 1.32-1.67) for the high-risk versus low-risk subsets (P = 0.009). Within the high-risk subset, 56% (5 of 9) of those who were FCXM T negative B positive experienced early regraft loss. A positive B cell FCXM has an adverse clinical impact only for high-risk regraft recipients. Pretransplant panel reactive antibody levels, pregnancy, number of blood transfusions between grafts, repeat donor HLA mismatches, and regraft recipient HLA mismatches did not correlate with early regraft loss. We conclude that kidney regraft survival rates in low-risk recipients (PGST >3 months/FCXM negative or positive [T and/or B cell] and PGST < or = 3 months/FCXM negative) approach primary graft survival rates and justify retransplantation, but the rate in high-risk regraft candidates (PGST < or =3 months/FCXM positive T and/or B cell) suggests that retransplantation should be performed only with a negative FCXM.

Female↗
PubMed1996

Tumor necrosis factor beta gene polymorphism and early primary kidney allograft loss.

The purpose of this study was to examine the association of TNFB alleles and genotypes in recipients experiencing early cadaveric kidney graft loss and non-early graft loss. Because the TNFB1 allele is associated with increased production of the TNF beta lymphotoxin following PHA mitogenic stimulation in vitro, the frequency of this allele was examined in renal transplant recipients experiencing early graft loss. A similar expression of TNFB alleles and genotypes was found in the early regraft loss group (< or = 3 months; n = 16) and non-early graft loss group (n = 81). We conclude that alleles of the TNFB gene are not risk factors for early cadaveric kidney graft loss.

Female↗
PubMed1996

When perfectly HLA-matched kidneys are refused for transplant: implications for a national cooperative sharing system.

BACKGROUND: The transplant community attempts to maximize overall renal graft survival rates through nationwide sharing of perfectly-matched cadaveric kidneys. Although the number of such transplants is determined annually, the number available but not transplanted has never been assessed. There has also been no verification of the widespread claim that kidneys transplanted as paybacks for perfect matches are inferior. STUDY DESIGN: From records of the United Network for Organ Sharing, a complete accounting of six-antigen-matched kidney disposition was obtained, including a frequency distribution of reasons for refusal given when kidneys were refused for matched patients. Actuarial graft survival (GS) rates for matched, payback, and other cadaveric renal transplants were determined. RESULTS: Of the six-antigen-matched kidneys available, 97 percent were transplanted; 71 percent of those were accepted for matched patients. The two-year GS rate for matched patients was 84 percent, significantly higher than that for kidneys available for matched patients but transplanted into other patients (71.3 percent) and that for all other cadaveric kidneys (75.5 percent). Most reasons for refusal were related to donor quality. Kidneys refused for such reasons showed a 67.7 percent two-year GS rate in nonmatched patients and the highest rates of acute and chronic rejection and primary failure. The two-year GS rate for kidneys accepted as paybacks for matched kidneys (75.7 percent) was equivalent to that for all non-matched cadaveric kidneys (75.5 percent). CONCLUSIONS: If all normal-quality grafts refused for perfectly matched patients during 1990 through 1992 had been accepted for those patients, the number of transplants with typically superior survival rates could have increased by 25 percent, from 1,365 to 1,704. The payback requirement of the United Network for Organ Sharing does not seem to reduce the overall benefits of sharing perfectly matched kidneys nationwide.

Cadaver↗
PubMed1990

The flow cytometric crossmatch and early renal transplant loss.

Data from this retrospective study indicate that a positive two-color T and/or B cell flow cytometric crossmatch (FCXM) is predictive of early renal allograft loss (less than 2 months) in cadaveric kidney donor recipients who had a negative crossmatch by the antihuman globulin complement-dependent cytotoxicity technique. Among 90 cadaveric kidney donor recipients (67 primary, 23 regrafts), 14 (8 primary, 6 regrafts) lost their renal allografts within 2 months, and 10 of the 14 were FCXM positive and HLA sensitized. The remaining 76 allografts survived beyond 2 months, 12 of which were FCXM-positive. Thus, the FCXM sensitivity rate for detecting early graft loss was 71%, and the specificity rate was 84%. Cadaveric graft-loss rates at 2 months were 33% for primary and 60% for FCXM-positive regrafts in contrast to 7% for primary and 0% for FCXM-negative regrafts. The difference in early graft loss between FCXM-positive and FCXM-negative recipients was statistically significant (P less than 0.0001). Subset analyses of FCXM-positive graft recipients indicate: (1) previous early graft loss contraindicates transplantation of an FXCM-positive regraft (P = 0.03); and (2) panel reactive antibody (PRA) less than or equal to 10% at crossmatch is not associated with early graft loss (P = 0.04). There was no significant difference in 1-year graft survival between primary and regrafts in either FCXM-negative recipients (85% vs. 77%, respectively) or FCXM-positive recipients (67% vs. 40%). All 12 of the FCXM-positive primary and regrafts that survived 2 months continued to function at 2 years. Stepwise logistic regression analysis of 5 independent predictor variables (FCXM status, gender, primary vs. regraft status, PRA level, and HLA mismatched antigens) indicated that the FCXM test was the best predictor of early graft loss. When FCXM results of the 90 cadaveric graft recipients were ranked in three groups, an FCXM channel shift of 29 or greater (third tertile) on a 1024 channel log scale was associated with a 7.0-fold (95% confidence interval 1.9-25.5) increased risk of early graft failure when compared to the first two tertiles. These data indicate that the FCXM offers an additional approach for identifying sensitized patients at risk of early renal allograft loss.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Serological identification of thymocyte differentiation antigens.

We have examined subfractions of human thymocytes for the expression of novel differentiation antigens. Non-HLA alloantisera procured from multiparous women served as antibody probes. Thymocytes from five individuals were sequentially separated by discontinuous Percoll density gradient centrifugation and a peanut agglutinin (PNA) panning technique. Subfractions were selected and examined for their relative intensity of HLA class I and CD1 antigens as determined by cytofluorometric analysis. Two subfractions were characterized as follows: an immature population (Fr6 PNA-) expressed a high level of CD1 (OKT6 binding) antigen and a low level of class I HLA antigen; and a more mature fraction (Fr3 PNA-) expressed minimal amounts of CD1 antigen and relatively high levels of HLA class I molecules. Fr6 PNA+ and Fr3 PNA- thymocytes were tested for their reactivity with a panel of non-HLA alloantibodies as determined by cytofluorometric analysis. We observed that three alloantibodies demonstrated strong fluorescence staining with Fr6 PNA+ thymocytes only, whereas three other alloantibodies reacted with both the Fr6 PNA+ and the Fr3 PNA- subfractions. All six alloantibodies failed to react with peripheral T cells. However, the six antibodies did react with a panel of cultured T lymphoblastoid leukemic cells and fresh leukemic T cells. Blocking studies demonstrated that these alloantibodies do not bind beta 2-microglobulin-associated determinants. These results suggest that the alloantibodies detect thymocyte differentiation antigens (TDA) that are shared by or are cross-reactive with antigens expressed on certain leukemia T cells. The non-beta 2m-associated TDA antigens are not expressed on normal resting T cells.

Antigens, CD1↗
PubMed1984

Utilization of murine peripheral blood lymphocytes for H-2 typing.

We adapted the NIH Standard Protocol for HLA-A, B, C typing to perform murine H-2 typing. The assay is direct, measuring the cytotoxicity of the antiserum/cell/complement reaction with a supravital dye. This method is advantageous because it: utilizes peripheral blood lymphocytes (PBL) obtained from the tail vein; uses microliter volumes of antiserum; is practical because the formalin fixed reactions need not be read immediately; involves standard and inexpensive cytotoxicity techniques; is easily interpreted and is readily reproducible.

Animals↗
PubMed1982

Alloantisera detect HLA-A-B-C and non-HLA differentiation antigens on human thymocytes.

Human thymocytes (THY) were examined for the expression of HLA-A,B,C antigens on their cell surface by using tissue typing alloantisera in the microcytotoxicity assay. Approximately 80% of the total THY population demonstrated antibody-mediated, C-dependent lysis with several alloantisera for each HLA-A,B,C specificity. The HLA phenotype of THY was verified by HLA typing autologous peripheral blood lymphocytes (PBL) from the thymus donor. Thymus tissue and PBL were obtained from cardiac surgical patients ranging in age from 3 mo to 12 yr. The capacity of THY to absorb HLA alloantibody was also demonstrated. Cross-absorption studies performed on PBL and THY by using HLA typing sera produced two important findings: 1) HLA typing sera that are devoid of non-HLA THY-specific antibody can be used to HLA type THY and 2) selected non-HLA sera from multiparous women, and selected HLA typing sera absorbed with PRL or platelets can be used to detect THY differentiation antigens. Taken together, cytotoxicity data, absorption capacities, cross-absorption studies, and statistical analysis indicate that HLA-A,B,C alloantigens and non-HLA polymorphic differentiation antigens detected by alloantisera are co-expressed on the cell surface of the majority of human THY.

Antibody Specificity↗
PubMed1980

Alloantigens of the human T (HT) genetic region of the HLA linkage group.

This article describes an approach that characterizes alloantisera reactive with new determinants on mitogen-activated human lymphocytes. These markers, which are tentatively called HT-antigens, are different from the classical HLA-A,C,C, and DR antigens but are associated with beta 2-microglobulin. Several alloantisera were tested extensively on lymphocytes that were treated initially with an antigen-blocking technique using turkey anti-beta 2-microglobulin and turkey anti-p29,34 sera or with an antigen-modulation technique using xeno- and alloantisera. It was concluded that these tested antisera recognized three different determinants (HT1, HT3, and HT (1 + 3) that appeared to segregate with the HLA-A locus of the HLA haplotype. HT antigens may be analogous to the murine TL-Qa antigens since HT antigens are associated with beta 2-microglobulin, are generally related to the HLA region, and are expressed on mitogen activated T cells but not on resting T cells.

Absorption↗