A comprehensive list of recommendations is provided covering the technical and pretransplantation and posttransplantation monitoring of HLA antibodies in solid organ transplantation. The recommendations are intended to provide state-of-the-art guidance in the use and clinical application of recently developed methods for HLA antibody detection when used in conjunction with traditional methods.

Type 1 diabetes (T1D; or insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease with both genetic and environmental components. In addition to the human leukocyte antigen (HLA) complex, the single major genetic contributor of susceptibility, an unknown number of other unidentified genes are required to mediate disease. Although many loci conferring susceptibility to T1D have been mapped, their identification has proven problematic due to the complex nature of this disease. Our strategy for finding T1D susceptibility genes has been to test for human homologues of loci implicated in diabetes-prone NOD (non-obese diabetic) mice, together with application of biologically relevant stratification methods. We report here a new susceptibility locus, IDDM18, located near the interleukin-12 (IL-12)p40 gene, IL12B. Significant bias in transmission of IL12B alleles was observed in affected sibpairs and was confirmed in an independent cohort of simplex families. A single base change in the 3' UTR showed strong linkage disequilibrium with the T1D susceptibility locus. The IL12B 3' UTR alleles showed different levels of expression in cell lines. Variation in IL-12p40 production may influence T-cell responses crucial for either mediating or protecting against this and other autoimmune diseases.

Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children. Diabetes 49:1319-1324, 2000 T ype 1 diabetes is an autoimmune disease that results from the destruction of pancreatic islet ␤-cells in genetically predisposed individuals. A large proportion of the lifetime risk of type 1 diabetes is attributed to environmental agents (1,2), but the only virus shown unequivocally to be responsible for clinical disease is rubella following infection in utero of infants bearing the HLA haplotype B8-(DR3-DQ2) (3). Circulating insulin autoantibodies (IAA), GAD65 antibodies (GADAb), and tyrosine phosphatase IA-2 autoantibodies (IA-2Ab) are markers of islet autoimmunity that predict the T-cell-mediated destruction of ␤-cells (4-6). Peptides in these islet autoantigens that are recognized by T-cells may provide clues to environmental agents that trigger or exacerbate islet autoimmunity through the mechanism of molecular mimicry (7,8).Recently, we identified T-cell epitope peptides in tyrosine phosphatase IA-2 (IA-2) restricted by HLA-DR4 in individuals at risk for type 1 diabetes (9,10). The dominant epitope (amino acid [aa] 805-820) contains a core 9-aa sequence in which 5 aa are identical and 4 aa are homologous with a 9-aa sequence (aa 41-49) within virus protein (VP)7 of rotavirus (RV) serotype G3 and to a lesser extent in the G1 and G2 serotypes. Because the T-cell contact residues in these similar IA-2 and RV VP7 sequences appear to be identical (9), the potential exists for molecular mimicry. Furthermore, just NH 2 -terminal of this region in VP7 is a 12-aa sequence (11) strongly similar to a sequence in GAD65 (aa 117-128) (9) that is a T-cell epitope in HLA-DR4 transgenic mice (12) and DR4-DQ8 homozygous at-risk humans (13). All human RV serotypes in the GenBank database contain the GAD-related sequence. VP7, the major outer capsid protein of RV, is an important determinant of virulence and induces virus-neutralizing antibodies (14). However, elimination of RV infection is predominantly due to T-cells (15). The CD4 T-cell epitopes in VP7 are unknown, but in C57/Bl 6 and BALB/c mice, CD8 T-cell epitopes (15,16) map adjacent to the IA-2-and GAD-like sequences, confirming that this signal sequenc...