Quantified colocalization reveals heterotypic histocompatibility class I antigen associations on trophoblast cell membranes: relevance for human pregnancy.

Human placental syncytiotrophoblasts lack expression of most types of human leukocyte antigen (HLA) class I and class II molecules; this is thought to contribute to a successful pregnancy. However, the HLA class Ib antigens HLA-G, -E, and -F and the HLA class Ia antigen HLA-C are selectively expressed on extravillous trophoblast cells, and they are thought to play a major role in controlling feto-maternal tolerance. We have hypothesized that selective expression, coupled with the preferential physical association of pairs of HLA molecules, contribute to the function of HLA at the feto-maternal interface and the maternal recognition of the fetus. We have developed a unique analytical model that allows detection and quantification of the heterotypic physical associations of HLA class I molecules expressed on the membrane of human trophoblast choriocarcinoma cells, ACH-3P and JEG-3. Automated image analysis was used to estimate the degree of overlap of HLA molecules labeled with different fluorochromes. This approach yields an accurate measurement of the degree of colocalization. In both JEG-3 and ACH-3P cells, HLA-C, -E, and -G were detected on the cell membrane, while the expression of HLA-F was restricted to the cytoplasm. Progesterone treatment alone induced a significant increase in the expression level of the HLA-G/HLA-E association, suggesting that this heterotypic association is modulated by this hormone. Our data shows that the cell-surface HLA class I molecules HLA-G, -E, and -C colocalize with each other and have the potential to form preferential heterotypic associations.

Waiting for organ transplantation: results of an analysis by an Institute of Medicine Committee.

One of the most visible and contentious issues regarding the fairness of the original system of organ procurement and allocation is the argument that it resulted in great disparities in the total amount of time a patient waited for an organ (i.e. the time from registration at a transplantation center to transplant), depending on where he or she lived. In an attempt to resolve this debate, Congress charged the National Academy of Sciences, Institute of Medicine to perform an independent study of the original system and proposed rule changes. In an analysis of approximately 68,000 transplant waiting list records, the committee developed several conclusions and recommendations largely specific to liver transplantation policies. The purpose of this paper is to describe both the results of the study and the statistical foundations of the mixed-effects multinomial logistic regression model that led to the committee's conclusions.