Impact of allele-specific anti-human leukocyte antigen class I antibodies on organ allocation.

Technological advances in the field of histocompatibility have allowed us to define anti-human leukocyte antigen (HLA) antibody specificity at the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6726 consecutive serum samples from 2953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation. Out of 17 class I HLA antigens represented by >1 allele in the LABScreen single antigen bead assay, 12 had potential allele-specific reactivity. Taking advantage of our unbiased cohort of deceased donor-candidate testing (123,135 complement-dependent cytotoxicity crossmatches between 2014 and 2017), we estimated that the presence of allele-specific antibody detected using a single antigen bead assay (median fluorescence intensity, >3000) against only the rare allele was a poor predictor of a positive complement-dependent cytotoxicity crossmatch, with a positive predictive value of 0% to 7%, compared with 52.5% in allele-concordant class I HLA antibodies against A or B locus antigens. Further, we confirmed allele-specific reactivity using flow crossmatch in 3 scenarios: A11:01/A11:02, A68:01/A68:02, and B44:02/B44:03. Our results suggest that allele-specific antibodies may unnecessarily exclude transplant candidates (up to 10%) from organ offers by overcalling unacceptable antigens; incorporation of selective reactivity pattern in allocation may promote precision matching and more equitable allocation.

Phenotypic plasticity and evolutionary potential in somatic cells of Armillaria gallica.

Somatic cells of Armillaria gallica fruit bodies have been shown to possess different genotypes for molecular-marker and mating-type loci. Here we report experiments on six quantitative traits and demonstrate that somatic cells of fruit bodies possess almost as much genetic variation for growth rate and phenotypic plasticity as do spores, the products of meiosis. Genetically distinct somatic cells therefore have the potential to grow at different rates relative to one another during primordial fruit body formation. This may confer an advantage on all cell lines within a fruit body, not just those that happen to grow better under a particular set of conditions. To our knowledge, genetic variation for fitness-related traits that make up a single genetic individual has not been reported before.