RESUMEN
The updated Banff classification allows for the diagnosis of antibody-mediated rejection (AMR) in the absence of peritubular capillary C4d staining. Our objective was to quantify allograft loss risk in patients with consistently C4d-negative AMR (n = 51) compared with C4d-positive AMR patients (n = 156) and matched control subjects without AMR. All first-year posttransplant biopsy results from January 2004 through June 2014 were reviewed and correlated with the presence of donor-specific antibody (DSA). C4d-negative AMR patients were not different from C4d-positive AMR patients on any baseline characteristics, including immunologic risk factors (panel reactive antibody, prior transplant, HLA mismatch, donor type, DSA class, and anti-HLA/ABO-incompatibility). C4d-positive AMR patients were significantly more likely to have a clinical presentation (85.3% vs. 54.9%, p < 0.001), and those patients presented substantially earlier posttransplantation (median 14 [interquartile range 8-32] days vs. 46 [interquartile range 20-191], p < 0.001) and were three times more common (7.8% vs 2.5%). One- and 2-year post-AMR-defining biopsy graft survival in C4d-negative AMR patients was 93.4% and 90.2% versus 86.8% and 82.6% in C4d-positive AMR patients, respectively (p = 0.4). C4d-negative AMR was associated with a 2.56-fold (95% confidence interval, 1.08-6.05, p = 0.033) increased risk of graft loss compared with AMR-free matched controls. No clinical characteristics were identified that reliably distinguished C4d-negative from C4d-positive AMR. However, both phenotypes are associated with increased graft loss and thus warrant consideration for intervention.
Asunto(s)
Complemento C4b/inmunología , Rechazo de Injerto/etiología , Isoanticuerpos/inmunología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias , Adulto , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Isoanticuerpos/sangre , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de RiesgoRESUMEN
Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.
Asunto(s)
Anticuerpos/inmunología , Incompatibilidad de Grupos Sanguíneos/epidemiología , Rechazo de Injerto/etiología , Antígenos HLA/inmunología , Trasplante de Riñón/legislación & jurisprudencia , Trasplante de Riñón/estadística & datos numéricos , Donadores Vivos/provisión & distribución , Adulto , Incompatibilidad de Grupos Sanguíneos/diagnóstico , Incompatibilidad de Grupos Sanguíneos/inmunología , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Incidencia , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
The impact of donor-specific HLA alloantibodies (DSA) on short- and long-term liver transplant outcome is not clearly defined. While it is clear that not all levels of allosensitization produce overt clinical injury, and that liver allografts possess some degree of alloantibody resistance, alloantibody-mediated adverse consequences are increasingly being recognized. To better define the current state of this topic, we assembled experts to provide insights, explore controversies and develop recommendations for future research on the consequences of DSA in liver transplantation. This article summarizes the proceedings of this inaugural meeting. Several insights emerged. Acute antibody-mediated rejection (AMR), although rarely diagnosed, is increasingly understood to overlap with T cell-mediated rejection. Isolated liver allograft recipients are at increased risk of early allograft immunologic injury when preformed DSA are high titer and persist posttransplantation. Persons who undergo simultaneous liver-kidney transplantation are at risk of renal AMR when Class II DSA persist posttransplantation. Other under-appreciated DSA associations include ductopenia and fibrosis, plasma cell hepatitis, biliary strictures and accelerated fibrosis associated with recurrent liver disease. Standardized DSA testing and diagnostic criteria for both acute and chronic AMR are needed to distil existing associations into etiological processes in order to develop responsive therapeutic strategies.
Asunto(s)
Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Isoanticuerpos/inmunología , Hepatopatías/inmunología , Trasplante de Hígado , Guías de Práctica Clínica como Asunto , Donantes de Tejidos , Humanos , Hepatopatías/cirugía , Pronóstico , Informe de InvestigaciónRESUMEN
Renal transplantation in patients with antiphospholipid antibodies has historically proven challenging due to increased risk for thrombosis and allograft failure. This is especially true for patients with antiphospholipid antibody syndrome (APS) and its rare subtype, the catastrophic antiphospholipid antibody syndrome (CAPS). Since a critical mechanism of thrombosis in APS/CAPS is one mediated by complement activation, we hypothesized that preemptive treatment with the terminal complement inhibitor, eculizumab, would reduce the extent of vascular injury and thrombosis, enabling renal transplantation for patients in whom it would otherwise be contraindicated. Three patients with APS, two with a history of CAPS, were treated with continuous systemic anticoagulation together with eculizumab prior to and following live donor renal transplantation. Two patients were also sensitized to human leukocyte antigens (HLA) and required plasmapheresis for reduction of donor-specific antibodies. After follow-up ranging from 4 months to 4 years, all patients have functioning renal allografts. No systemic thrombotic events or early graft losses were observed. While the appropriate duration of treatment remains to be determined, this case series suggests that complement inhibitors such as eculizumab may prove to be effective in preventing the recurrence of APS after renal transplantation.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Antifosfolípido/prevención & control , Inactivadores del Complemento/uso terapéutico , Rechazo de Injerto/prevención & control , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/prevención & control , Adulto , Síndrome Antifosfolípido/etiología , Estudios de Seguimiento , Rechazo de Injerto/etiología , Humanos , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Recurrencia , Inducción de RemisiónRESUMEN
Antibodies to donor HLA (human leukocyte antigen) and/or ABO antigens were a contraindication to transplantation of most organs for decades. Desensitization protocols have shown the ability to produce reduction of such antibodies sufficient to achieve a successful transplantation. The two major protocols in use are high-dose IVIg or plasmapheresis with low-dose IVIg. The protocols differ in the basic treatment and, to some degree, in their application, but both use standard immunosuppressive agents as well as more recently developed adjunctive agents such as cell-depleting antibodies. Graft and patient survival with both types of protocol are comparable to that of non-sensitized patients, although desensitized patients do have a higher incidence of antibody-mediated rejection (AMR). Antibodies to donor antigens may persist after transplantation, and while the initial antibody titer represents the level of difficulty for successful desensitization, the strength of antibodies that persist after transplantation reflects the risk of AMR. Current protocols do not eliminate B cell clones specific for donor HLA; therefore, desensitized patients remain at an increased risk of antibody rebound if patients experience pro-inflammatory events. Therefore, ongoing antibody monitoring is crucial for early detection of antibody-mediated graft injury. Importantly, the results of numerous programs show that ABOi- and HLA-positive crossmatch renal transplantation, with proper desensitization, can be performed successfully. Further, in addition to increasing the rate of transplantation among sensitized patients, desensitization is providing insight into immunoregulatory processes and may provide information useful in diseases involving immune dysfunction.
Asunto(s)
Desensibilización Inmunológica , Rechazo de Injerto/prevención & control , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Humanos , Inmunoglobulinas Intravenosas/inmunología , Factores Inmunológicos/inmunologíaRESUMEN
A 43-year-old patient with end-stage renal disease, a hypercoagulable condition and 100% panel reactive antibody was transferred to our institution with loss of hemodialysis access and thrombosis of the superior and inferior vena cava, bilateral iliac and femoral veins. A transhepatic catheter was placed but became infected. Access through a stented subclavian into a dilated azygos vein was established. Desensitization with two cycles of bortezomib was undertaken after anti-CD20 and IVIg were given. A flow-positive, cytotoxic-negative cross-match live-donor kidney at the end of an eight-way multi-institution domino chain became available, with a favorable genotype for this patient with impending total loss of a dialysis option. The patient received three pretransplant plasmapheresis treatments. Intraoperatively, the superior mesenteric vein was the only identifiable patent target for venous drainage. Eculizumab was administered postoperatively in the setting of antibody-mediated rejection and an inability to perform additional plasmapheresis. Creatinine remains normal at 6 months posttransplant and flow cross-match is negative. In this report, we describe the combined use of new agents (bortezomib and eculizumab) and modalities (nontraditional vascular access, splanchnic drainage of graft and domino paired donation) in a patient who would have died without transplantation.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Ácidos Borónicos/uso terapéutico , Fallo Renal Crónico/terapia , Trasplante de Riñón , Donadores Vivos , Inhibidores de Proteasas/uso terapéutico , Pirazinas/uso terapéutico , Obtención de Tejidos y Órganos/métodos , Adulto , Anticuerpos/sangre , Anticuerpos/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antígenos CD20/inmunología , Bortezomib , Catéteres de Permanencia , Creatinina/sangre , Desensibilización Inmunológica/métodos , Drenaje , Quimioterapia Combinada , Femenino , Vena Femoral , Humanos , Vena Ilíaca , Inmunoglobulinas Intravenosas/uso terapéutico , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/inmunología , Plasmaféresis , Circulación Esplácnica , Terapias en Investigación , Vena Cava Inferior , Vena Cava Superior , Trombosis de la Vena/complicacionesRESUMEN
Identification of factors responsible for an increase in the breadth or strength of HLA-specific antibody (HSA) is critical to the continued successful management and transplantation of sensitized patients. A retrospective review of our HLA registry identified 107 patients with known HSA and sufficient information in their electronic patient record to determine the presence or absence of a proinflammatory event. The patients were stratified according to transplant status [sensitized and on the transplant waitlist (n = 65); immunosuppressed recipients of a positive crossmatch (+XM) transplant (n = 42)]. Eighty-three percent of waitlist candidates and 55% of sensitized kidney transplant recipients with a documented proinflammatory event had an associated increase in HSA. Interestingly, among patients with a culture-proven infection, 97% of the waitlist patients and 54.8% of +XM recipients had an associated rise in HSA. Overall, proinflammatory events were associated with a greater increase among waitlist patients than +XM recipients, 5.3-fold [IRR 5.25, (95% CI 4.03-6.85), p < 0.001] versus 2.5-fold [IRR 2.54, (95% CI 1.64-3.95), p < 0.001] increase in HSA. Therefore, sensitized patients known to have an infection or undergoing surgery should be monitored for expansion of HSA.
Asunto(s)
Anticuerpos/química , Antígenos HLA/química , Inflamación , Trasplante de Riñón/métodos , Anciano , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Inmunosupresores/uso terapéutico , Infecciones/etiología , Persona de Mediana Edad , Complicaciones Posoperatorias , Sistema de Registros , Estudios Retrospectivos , Listas de EsperaRESUMEN
We reviewed 116 surveillance biopsies obtained approximately 1, 3, 6 and 12 months posttransplantation from 50 +XM live donor kidney transplant recipients to determine the frequency of subclinical cell-mediated rejection (CMR) and antibody-mediated rejection (AMR). Subclinical CMR was present in 39.7% of the biopsies at 1 month and >20% at all other time points. The presence of diffuse C4d on biopsies obtained at each time interval ranged from 20 to 30%. In every case, where histological and immunohistological findings were diagnostic for AMR, donor-specific antibody was found in the blood, challenging the long-held belief that low-level antibody could evade detection due to absorption on the graft. Among clinical factors, only recipient age was associated with subclinical CMR. Clinical factors associated with subclinical AMR were recipient age, positive cytotoxic crossmatch prior to desensitization and two mismatches of HLA DR 51, 52 and 53 alleles. Surveillance biopsies during the first year post-transplantation for these high-risk patients uncover clinically occult processes and phenotypes, which without intervention diminish allograft survival and function.
Asunto(s)
Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Prueba de Histocompatibilidad/efectos adversos , Trasplante de Riñón/inmunología , Adulto , Alelos , Biopsia , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Creatinina/sangre , Estudios Transversales , Femenino , Estudios de Seguimiento , Antígenos HLA-DR/genética , Antígenos HLA-DR/inmunología , Cadenas HLA-DRB4 , Cadenas HLA-DRB5 , Humanos , Incidencia , Riñón/patología , Riñón/fisiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Desensitized patients are at high risk of developing acute antibody-mediated rejection (AMR). In most cases, the rejection episodes are mild and respond to a short course of plasmapheresis (PP) / low-dose IVIg treatment. However, a subset of patients experience severe AMR associated with sudden onset oliguria. We previously described the utility of emergent splenectomy in rescuing allografts in patients with this type of severe AMR. However, not all patients are good candidates for splenectomy. Here we present a single case in which eculizumab, a complement protein C5 antibody that inhibits the formation of the membrane attack complex (MAC), was used combined with PP/IVIg to salvage a kidney undergoing severe AMR. We show a marked decrease in C5b-C9 (MAC) complex deposition in the kidney after the administration of eculizumab.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Complemento C5/inmunología , Rechazo de Injerto/terapia , Trasplante de Riñón , Adulto , Anticuerpos Monoclonales Humanizados , Femenino , Rechazo de Injerto/inmunología , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Donadores Vivos , Masculino , Terapia RecuperativaRESUMEN
Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000-2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard-to-match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well-matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.
Asunto(s)
Glomerulonefritis por IGA/terapia , Glomerulonefritis/terapia , Fallo Renal Crónico/terapia , Trasplante de Riñón/métodos , Enfermedades Renales Poliquísticas/terapia , Obtención de Tejidos y Órganos/métodos , Trasplante Homólogo/métodos , Adulto , Femenino , Humanos , Donadores Vivos , Masculino , Persona de Mediana Edad , Reperfusión , Asignación de Recursos , Factores de TiempoRESUMEN
We examined rejection outcome and graft survival in 58 adult patients with acute cellular rejection Banff type I (ARI) or II (ARII), within 1 year after transplantation, with or without CD20-positive infiltrates. Antibody-mediated rejection was not examined. Of the 74 allograft biopsies, performed from 1999 to 2001, 40 biopsies showed ARI and 34 biopsies showed ARII; 30% of all the biopsies showed CD20-positive clusters with more than 100 cells, 9% with more than 200 cells and 5% with more than 275 cells. Patients with B cell-rich (>100 or >200/HPF CD20-positive cells) and B cell-poor biopsies (<50 CD20-positive cells/HPF) were compared. Serum creatinine and eGFR of B cell-rich (CD20 > 100/HPF) and B cell-poor were not significantly different at rejection, or at 1, 3, 6 and 12 months, and during additional 3 years follow-up after rejection, although higher creatinine at 1 year was noted in the >200/HPF group. Graft survival was also not different between B cell-rich and B cell-poor groups (p = 0.8 for >100/HPF, p = 0.9 for >200/HPF CD20-positive cells). Our data do not support association of B cell-rich infiltrates in allograft biopsies and worse outcome in acute rejection type I or II, but do not exclude the possible contribution of B cells to allograft rejection.
Asunto(s)
Antígenos CD20/inmunología , Rechazo de Injerto/patología , Supervivencia de Injerto/inmunología , Trasplante de Riñón/inmunología , Enfermedad Aguda , Adulto , Anciano , Linfocitos B/inmunología , Linfocitos B/patología , Creatinina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
A session of the 14 International Histocompatibility Workshop brought together experts representing the major clinical protocols, clinical research, and basic research dealing with overcoming the barrier of alloantibody in transplantation and in understanding the mechanisms by which those antibodies exert their effect on a transplanted organ. This report is an integration of the presentations of those scientists.
Asunto(s)
Antígenos HLA/inmunología , Inmunogenética , Inmunoglobulina G/inmunología , Isoanticuerpos/inmunología , Trasplante de Órganos , Antígenos HLA/genética , Humanos , Isoanticuerpos/genéticaRESUMEN
Antibody-mediated rejection (AMR) after desensitization for a positive crossmatch (+XM) live donor renal transplant can be severe and result in sudden onset oliguria and loss of the allograft. Attempts to rescue these kidneys using plasmapheresis (PP) and IVIg may be ineffective due to the magnitude of antibody burden that must be controlled to prevent renal thrombosis or cortical necrosis. We review our experience using splenectomy combined with PP/IVIg as rescue therapy for patients experiencing an acute deterioration in renal function and a rise in donor-specific antibody within the first posttransplant week after desensitization for a +XM. Five patients underwent immediate splenectomy followed by PP/IVIg and had return of allograft function within 48 h of the procedure. Emergent splenectomy followed by PP/IVIg may be an effective treatment for reversing severe AMR.
Asunto(s)
Rechazo de Injerto/terapia , Inmunosupresores/uso terapéutico , Isoanticuerpos/sangre , Trasplante de Riñón/inmunología , Esplenectomía , Adulto , Femenino , Rechazo de Injerto/tratamiento farmacológico , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/cirugíaRESUMEN
Subclinical antibody-mediated rejection (AMR) has been described in renal allograft recipients with stable serum creatinine (SCr), however whether this leads to development of chronic allograft nephropathy (CAN) remains unknown. We retrospectively reviewed data from 83 patients who received HLA-incompatible renal allografts following desensitization to remove donor-specific antibodies (DSA). Ten patients had an allograft biopsy showing subclinical AMR [stable SCr, neutrophil margination in peritubular capillaries (PTC), diffuse PTC C4d, positive DSA] during the first year post-transplantation; 3 patients were treated with plasmapheresis and intravenous immunoglobulin. Three patients had a subsequent rise in SCr and an associated biopsy with AMR; 5 others showed diagnostic or possible subclinical AMR on a later protocol biopsy. One graft was lost, while remaining patients have normal or mildly elevated SCr 8-45 months post-transplantation. However, the mean increase in CAN score (cg + ci + ct + cv) from those biopsies showing subclinical AMR to follow-up biopsies 335 +/- 248 (SD) days later was significantly greater (3.5 +/- 2.5 versus 1.0 +/- 2.0, p = 0.01) than that in 24 recipients of HLA-incompatible grafts with no AMR over a similar interval (360 +/- 117 days), suggesting that subclinical AMR may contribute to development of CAN.
Asunto(s)
Anticuerpos/inmunología , Rechazo de Injerto/diagnóstico , Antígenos HLA-A/inmunología , Histocompatibilidad , Trasplante de Riñón , Insuficiencia Renal/diagnóstico , Adulto , Negro o Afroamericano , Anciano , Complemento C4b/análisis , Creatinina/sangre , Femenino , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/análisis , Insuficiencia Renal/inmunología , Insuficiencia Renal/patología , Trasplante Homólogo , Población BlancaRESUMEN
Biopsies of ABO-incompatible and positive crossmatch (HLA-incompatible) renal allografts were retrospectively examined to compare results of C4d and C3d staining, and the correlation between such staining and histologic findings suggestive of antibody-mediated rejection (AMR). A total of 75 biopsies (55 protocol, 17 for graft dysfunction, 3 for other indications) of 24 ABO-incompatible grafts and 244 biopsies (103 protocol, 129 for graft dysfunction, 12 for other indications) of 66 HLA-incompatible grafts were examined; all were stained for C4d and approximately 40% for C3d. In ABO-incompatible grafts, 80% of protocol biopsies and 59% performed for graft dysfunction showed C4d staining in peritubular capillaries (PTC); this staining was not correlated with neutrophil margination in PTC. In HLA-incompatible grafts, PTC C4d was present in 26% of protocol biopsies and 60% of biopsies for graft dysfunction; 92% of biopsies with >1+ (0-4+ scale), diffuse PTC C4d had > or =1+ margination and/or thrombotic microangiopathy (TMA), compared with 12% of C4d-negative biopsies. C3d was somewhat more predictive of margination than C4d in ABO-incompatible, but not HLA-incompatible, grafts. In summary, while PTC C4d deposition indicates probable AMR in biopsies of HLA-incompatible grafts, including protocol biopsies, there is no histologic evidence that C4d deposition is correlated with injury in most ABO-incompatible grafts.
Asunto(s)
Incompatibilidad de Grupos Sanguíneos/inmunología , Complemento C3d/metabolismo , Complemento C4/metabolismo , Antígenos HLA/inmunología , Enfermedades Renales/patología , Trasplante de Riñón/inmunología , Trasplante de Riñón/patología , Sistema del Grupo Sanguíneo ABO/inmunología , Sistema del Grupo Sanguíneo ABO/metabolismo , Anticuerpos/inmunología , Biopsia , Incompatibilidad de Grupos Sanguíneos/metabolismo , Rechazo de Injerto/inmunología , Enfermedades Renales/inmunología , Enfermedades Renales/metabolismo , Enfermedades Renales/cirugía , Trasplante Homólogo/inmunologíaAsunto(s)
Prueba de Histocompatibilidad , Inmunoglobulinas Intravenosas/uso terapéutico , Trasplante de Riñón/fisiología , Donadores Vivos , Plasmaféresis , Adulto , Anciano , Terapia Combinada , Creatinina/sangre , Femenino , Estudios de Seguimiento , Humanos , Isoanticuerpos/sangre , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana Edad , Grupos Raciales , Estudios Retrospectivos , Tacrolimus/uso terapéutico , Factores de Tiempo , Estados UnidosRESUMEN
HLA typing was performed on 977 African Americans residing throughout most of the United States. Class I and class II antigens and class II alleles were defined for all individuals and class I alleles were determined for a subset of individuals. The occurrence of 854 of the individuals in family groups permitted direct counting of allele and haplotype frequencies. The data were analyzed for antigen, allele, and haplotype frequencies; recombination frequencies; segregation distortion; distribution of haplotype frequencies; linkage disequilibria; and geographic distribution of DR antigens. Tables of the antigen, allele, the most common two and three point haplotypes, and 88 extended haplotypes that include class I and class II alleles are presented. Notable findings include a lower than expected frequency of recombination between the B and DR loci (theta= 0.0013), lower than expected frequency of inheritance (44.5% vs 54.5%) of the DRB1*1503; DQB1*0602 haplotype, lower than anticipated linkage disequilibrium values for DR; DQ haplotypes, and a skewed geographic distribution of DR antigens.