As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multimodal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000–10 000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort.

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Blood transfusions have an immunosuppressive effect on the recipient and induce changes in several immunological parameters. We studied the effect of homologous and autologous fresh plasma (FP), fresh frozen plasma (FFP), heparinized plasma, as well as the influence of red blood cells (RBC), CPDA-1, CPD, heparin, PAGGS-mannitol, SAG-mannitol and ADSOL on mitogen-induced lymphocyte transformation. Both homologous and autologous FP and FFP decreased the PHA and ConA response of human lymphocytes (P < 0.05). The PWM response was reduced by FP (P < 0.05). The mean t1/2 of plasma-induced suppression was approximately 38 h. Dose-dependent suppression rates were observed with pure CPDA-1 and CPD solutions. In contrast, heparinized plasma showed an elevated PHA- and ConA-induced transformation rate (P < 0.025), whereas PWM induction was unaffected. In addition, washed RBC, pure PAGGS-M, SAG-M and ADSOL solutions revealed no effect on the PHA response. Freezing, heating or recalcification of plasma resulted in an increase in the PHA response. Adenine was not immunosuppressive in vitro. We conclude that, in addition to unspecific mechanisms by CPDA-1 or CPD, an unknown plasma factor, which is susceptible to changes in temperature or storage conditions, suppresses the PHA-, PWM- or ConA-induced T-cell immune response. Further clinical studies are needed to correlate these observations with clinical phenomena.

Summary The Megacolon‐Syndrome is a hereditary disease of homozygous spotted rabbits (En En). Investigations have been performed on some special traits related to functional aspects of the gut in comparison to vital heterozygous spotted rabbits (En en). It was found that En En rabbits showed significantly reduced sodium absorption rates across the wall of the cecum. Consequently, the dry matter content of the ingesta was reduced at this location, whereas the content of the ashes was increased. These results indicate that a further important pathogenetic aspect of this hereditary disease is an undue liquification of ingesta in proximal parts of the large intestine. Severe clinical problems, however, resulted from obstipation. This is concluded to be a late complication due to and modified by different stressors of endogenic and exogenic origin. Thus there are some indications that an early site of spot‐gene related effects might be the small intestine. This segment of the bowel was shorter and had an increased dry matter proportion of its wall when compared with heterozygous spotted rabbits. But a decreased proportion of dry matter within the wall of the large intestine was found. The latter could be an effect of the hypothyreotic state of metabolism in En En rabbits.