RESUMEN
The Network for Pancreatic Organ donors with Diabetes (nPOD) programme was developed in response to an unmet research need for human pancreatic tissue obtained from individuals with type 1 diabetes mellitus and people at increased risk [i.e. autoantibody (AAb)-positive] for the disease. This necessitated the establishment of a type 1 diabetes-specific AAb screening platform for organ procurement organizations (OPOs). Assay protocols for commercially available enzyme-linked immunosorbent assays (elisas) determining AAb against glutamic acid decarboxylase (GADA), insulinoma-associated protein-2 (IA-2A) and zinc transporter-8 (ZnT8A) were modified to identify AAb-positive donors within strict time requirements associated with organ donation programmes. These rapid elisas were evaluated by the international islet AAb standardization programme (IASP) and used by OPO laboratories as an adjunct to routine serological tests evaluating donors for organ transplantation. The rapid elisas performed well in three IASPs (2011, 2013, 2015) with 98-100% specificity for all three assays, including sensitivities of 64-82% (GADA), 60-64% (IA-2A) and 62-68% (ZnT8A). Since 2009, nPOD has screened 4442 organ donors by rapid elisa; 250 (5·6%) were identified as positive for one AAb and 14 (0.3%) for multiple AAb with 20 of these cases received by nPOD for follow-up studies (14 GADA+, two IA-2A(+) , four multiple AAb-positive). Rapid screening for type 1 diabetes-associated AAb in organ donors is feasible, allowing for identification of non-diabetic, high-risk individuals and procurement of valuable tissues for natural history studies of this disease.
Asunto(s)
Autoanticuerpos/sangre , Selección de Donante/normas , Ensayo de Inmunoadsorción Enzimática/normas , Donantes de Tejidos/provisión & distribución , Adolescente , Adulto , Área Bajo la Curva , Proteínas de Transporte de Catión/antagonistas & inhibidores , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/inmunología , Niño , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 1/cirugía , Femenino , Glutamato Descarboxilasa/antagonistas & inhibidores , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/inmunología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/antagonistas & inhibidores , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/genética , Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores/inmunología , Riesgo , Sensibilidad y Especificidad , Transportador 8 de ZincRESUMEN
Islet transplantation is a promising therapy used to achieve glycometabolic control in a select subgroup of individuals with type I diabetes. However, features that characterize human islet isolation success prior to transplantation are not standardized and lack validation. We conducted a retrospective analysis of 806 isolation records from 14 pancreas-processing laboratories, considering variables from relevant studies in the last 15 years. The outcome was defined as post-purification islet equivalent count, dichotomized into yields > or =315 000 or < or =220 000. Univariate analysis showed that donor cause of death and use of hormonal medications negatively influenced outcome. Conversely, pancreata from heavier donors and those containing elevated levels of surface fat positively influence outcome, as did heavier pancreata and donors with normal amylase levels. Multivariable logistic regression analysis identified the positive impact on outcome of surgically intact pancreata and donors with normal liver function, and confirmed that younger donors, increased body mass index, shorter cold ischemia times, no administration of fluid/electrolyte medications, absence of organ edema, use of University of Wisconsin preservation solution and a fatty pancreas improves outcome. In conclusion, this multicenter analysis highlights the importance of carefully reviewing all donor, pancreas and processing parameters prior to isolation and transplantation.