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Biomedical subjects

D L Phelan

Publications and source records attributed to D L Phelan.

13 recordsLinked to original sources
PubMed1998

Effect of development of antibodies to HLA and cytomegalovirus mismatch on lung transplantation survival and development of bronchiolitis obliterans syndrome.

OBJECTIVE: A retrospective analysis was performed to examine the role of HLA antibodies and cytomegalovirus mismatch on the development of bronchiolitis obliterans syndrome and survival after lung transplantation. METHODS: Of 339 consecutive lung transplantations performed over a 102-month interval, 301 patients survived at least 3 months. There was a minimum follow-up period of 13 months. Bronchiolitis obliterans syndrome was defined as a decline in forced expiratory volume in 1 second less than 80% of posttransplantation baseline and/or histologic presence of obliterative bronchiolitis and was defined as occurring "early" if documented within 3 years of transplantation. Variables analyzed included preoperative donor and recipient cytomegalovirus status and the development of antibodies to human leukocyte antigens after transplantation. Microcytotoxicity was used to determine the presence of antibodies to human leukocyte antigens. Variables were subjected to Kaplan-Meier analysis to determine their impact on freedom from bronchiolitis obliterans syndrome and survival. RESULTS: The development of antibodies to human leukocyte antigens after transplantation correlated significantly with bronchiolitis obliterans syndrome (P = .02). The development of antibodies to human leukocyte antigens did not affect survival (P = .33) unless they were detected within 2 years of transplantation (P = .04). There was greater frequency of early bronchiolitis obliterans syndrome in cytomegalovirus seronegative patients who received allografts from seropositive donors compared with all other combinations (P = .02). There was also a trend toward worse survival of cytomegalovirus seronegative patients who received allografts from seropositive donors (P = .13). CONCLUSION: These data suggest that bronchiolitis obliterans syndrome is the result of an immune-mediated process in which HLA antibodies and cytomegalovirus may play a significant role.

Actuarial Analysis↗
PubMed1997

Cytomegalovirus and HLA-A, B, and DR locus interactions: impact on renal transplant graft survival.

Graft failure rates for renal transplantations performed between 1989 and 1994 and recorded in the US Renal Data System database were retrospectively evaluated for interactions between cytomegalovirus and HLA-A, B, and DR loci. Twelve significant interactions were observed. There were significantly greater risks of graft failure for the total effect of cytomegalovirus and donor or matched HLA-DR9, recipient or matched HLA-B-51, and matched HLA-B13. We conclude that further study of renal transplants with these combinations of cytomegalovirus and HLA loci is needed to determine whether the observed interactions should be taken into consideration when matching donors with recipients.

Adult↗
PubMed1995

HLA typing in women with breast implants.

Since the 1970s, anecdotal reports have described a relatively small number of women who received silicone gel breast implants and later developed either a recognized rheumatologic disease or unexplained symptoms suggestive of an autoimmune disorder. The study reported here examined whether there is any association between the symptoms seen in implant patients and HLA molecules. One-hundred and ninety-nine subjects were evaluated by HLA typing: symptomatic patients with implants (group I, n = 77), asymptomatic women with implants (group II, n = 37), healthy female volunteers without implants (group III, n = 54), and fibromyalgia patients without implants (group IV, n = 31). A statistically significant 68 percent of group I were positive for HLA-DR53, compared with 35 percent of group II and 52 percent of group III. The fibromyalgia patients were strikingly similar to group I women in terms of HLA-DR molecules, with 65 percent of group IV being positive for DR53. Group I also had a statistically significant increased frequency of HLA-DQ2. Asymptomatic women with implants (group II) had an increased frequency of DR1 and DQ1. In addition, 42 percent of symptomatic patients with implants formed autoantibodies to their own B cells; of these, 81 percent were DR53-positive. Although frequencies of capsular contracture and implant rupture were not significantly different in the two groups with implants, there were statistically significant associations in group I between contractures and ruptures and the presence of DR53 and B-cell autoantibodies. These data suggest that symptomatic patients with implants share important genetic characteristics (primarily HLA-DR53 positivity) that differentiate them from their asymptomatic counterparts. DR53 may be a marker of women who are predisposed by their HLA genotype to develop symptoms following exposure to silicone gel breast implants.

Adolescent↗
PubMed1993

Characterization of antiidiotypic antibodies to donor HLA that develop after liver transplantation.

Several studies have reported the development of antiidiotypic antibodies to anti-HLA alloantibodies in renal allograft transplant recipients, postulating their potential beneficial role in allograft survival. In order to evaluate the role of anti-HLA antiidiotypic antibodies in human liver transplant recipients and to differentiate them from circulating soluble donor HLA antigens, sera obtained from liver recipients, both pre- and posttransplantation, were analyzed for cytotoxicity inhibitory activity against alloantisera to mismatched donor HLA antigens. Prior to cytotoxicity inhibition assays, sera were absorbed with W6/32 coupled sepharose in order to remove circulating HLA antigens. Antiidiotypic antibodies to anti-HLA class I antibodies were detected in the sera of 7 out of 9 recipients, and antibodies to anti-HLA class II were found in the sera of 4 out of 7 recipients. Antiidiotypic antibodies were detected only during the immediate posttransplantation period. The specific inhibitory activity noted against both HLA class I and II mismatches showed no detectable preference for either HLA class or locus. Furthermore, the antiidiotypic antibodies to HLA developed in liver recipients also inhibited alloantisera to HLA-specific public epitopes or crossreactive groups (CREGS). Cytotoxicity inhibition by posttransplant sera was not mediated by circulating HLA antigens since absorption of the sera with monoclonal anti-HLA framework reagents did not change the specific inhibition of the alloantisera. In addition, the immunoglobulin fraction of the posttransplant sera retained its ability to inhibit cytotoxicity by donor-specific alloantisera. Thus these studies indicate that the development of antiidiotypic antibodies to anti-HLA is common during the immediate period following liver transplantation, even though circulating donor HLA antigens are present. The presence of circulating donor HLA antigens and the development of antiidiotypic antibodies to donor-specific anti-HLA during this period may be important for the successful adaptation of mismatched liver allografts.

Antibodies, Anti-Idiotypic↗
PubMed1989

Association of antiidiotypic antibody with successful second transplant of a kidney sharing HLA antigens with the previous hyperacutely rejected first kidney.

The evolution of HLA antibodies and autoantiidiotypic antibodies (AB2) were studied during an 18-month period in a patient who hyperacutely rejected an HLA-A2-positive kidney, but tolerated a second HLA-A2-positive kidney one year later. Following rejection of the first kidney, the patient's serum contained an HLA-A2 antibody that reacted with 100% of HLA-A2-positive panel cells. After several months, the HLA-A2 antibody activity was precipitously lost over a one-month period and could no longer be identified by sensitive lymphocytotoxicity procedures. Approximately one year later, the patient received a second HLA-A2-positive kidney that has survived for a 2-year period and was not associated with significant rejection episodes during the early posttransplantation period. Prior to and episodically following the second transplant, the patient's sera contained antiidiotypic-like antibodies that specifically inhibited HLA alloantibodies directed against HLA-A2. AB2, with specificity for a putative idiotype on HLA-A2 alloantibodies, existed concurrently with other HLA alloantibodies in the patient's serum that had not been lost over the course of several months. This case study demonstrates a temporal association between the loss of a specific HLA antibody and the development of an AB2 with inhibitory specificity for the antibody. The study also confirms that anamnestic responses to donor-specific antigens do not always occur in previously alloimmunized patients rechallenged with the same HLA antigens.

Adult↗
PubMed1989

The development and specificity of antiidiotypic antibodies in renal transplant recipients receiving single-donor blood transfusions.

Multiple pretransplant sera obtained from alloimmunized renal transplant recipients were tested for the presence of antiidiotypic-like antibodies (AB2) that inhibit donor-specific HLA antibodies in the microlymphocytotoxicity assay. Fourteen patients received repetitive single-donor blood transfusions (SDT). In this patient group, sera were collected prior to each blood transfusion and prior to transplantation. Three additional patients were studied in whom prior donor-specific HLA antibodies had been lost over a period of 6 months preceding transplantation. Donor-specific AB2-like antibodies were found in the sera of 13/14 SDT patients who did not develop HLA antibodies, and in the 3 patients who had lost donor-specific HLA antibodies. All patients had received prior random blood transfusions in the year preceding the study. Five (38%) of the SDT patients had detectable donor-specific AB2 prior to the initiation of single-donor blood transfusion, presumably related to previous blood transfusions. In the remaining six SDT patients in whom complete serum sets were available, AB2 always appeared after the first blood transfusion. The specificity of HLA antibodies inhibited by AB2 was studied, and antibodies against HLA-A, -B, -C, -DR, and DQw were all identified. Thus, there was no predilection for patients to develop AB2 against locus-specific HLA gene products. This study also confirms the apparent polymorphism of putative crossreactive idiotypes. Approximately 25% of donor-specific HLA antibodies were not inhibited by relevant AB2. This study confirms and extends previous observations that alloimmunization is associated in many patients with the development of antiidiotypic-like antibodies that are capable of inhibiting the binding and cytotoxicity of HLA alloantibodies.

Antibodies, Anti-Idiotypic↗
PubMed1986

Prediction of crossmatch outcome in highly sensitized dialysis patients based on the identification of serum HLA antibodies.

High levels of allosensitization (greater than 50%), which often occur in dialysis patients awaiting renal transplant, make donor selection difficult. Such patients may be included in elaborate protocols in which they are crossmatched with all available ABO compatible donors, or crossmatching may be deferred until a very-well-matched donor becomes available. The former approach of random crossmatching is costly and inefficient, while the latter approach may overlook crossmatch-compatible donors. We believe that the identification of antibodies present in highly reactive sera and the use of this information in donor selection would increase the frequency of crossmatch-negative donors for these patients. In this study eleven sera, reactive with 70% to 100% of a random cell panel, were obtained from multiply transfused dialysis patients. Sera were analyzed by standard (CDC) and antiglobulin augmented (AHG-CDC) lymphocytotoxicity, and by differential absorption with HLA-typed platelets. All sera contained only one or two antibodies directed against the high frequency public HLA epitopes, accounting for 85% to 100% of each serum's total reactivity. These characterized sera were crossmatched with 114 random normal donors. The frequency of negative crossmatches was 20.5%. However, if the serum antibody data had been used to preselect donors for crossmatch--that is, to exclude donors that were likely to be positive--the negative crossmatch frequency would have increased to 86.4%. The use of the serum analysis data in donor selection would have reduced the total number of required crossmatches by 78%. Serum analysis correctly predicted the outcome of 95.6% of crossmatches performed with an average of 3% false positives and 1.3% false negatives. This approach to donor selection reduces unnecessary crossmatching and increases the likelihood of finding crossmatch-compatible donors for highly reactive patients.

ABO Blood-Group System↗