Rapid and strong de novo donor-specific antibody development in a lung transplant recipient: Short communication/case report.

A 66-yo female patient (typed B*39:01, 44:02) underwent first left single lung transplant (typed B*81:01, 15:17) on 02/07/2016 with negative for DSA in current and historical samples. On 02/17/2016 strong de novo DSA (MFI=15,200, C1q+) to B81 were detected. The recipient has two children typed B*07:02, 44:02 B*27:03, 39:01, and had received multiple vaccinations. Twinrix, Zostavax and MMR vaccines contain viruses grown on live human lung fibroblasts (MRC-5, typed B*07:02, 44:02, and WI-38, typed B*08:01, 58:01). Each dose of vaccine used for injection is known to contain protein components of fibroblasts including HLA. Most likely rapid de novo DSA development is due to booster effect produced by five exposures to mismatched B locus alleles which share the following epitopes: 70IAQ, 65QIA, 65QIA+76esn, 69aa+80n, and 163ew+73te. The later three consist of paired non-self and self eplets. Although likelihood of bystander effect produced by multiple vaccinations is low its impact cannot be ruled out.

Evaluation of Alemtuzumab Versus Basiliximab Induction: A Retrospective Cohort Study in Lung Transplant Recipients.

BACKGROUND: Acute cellular rejection (ACR) is a major early complication after lung transplantation (LT) and is a risk factor for chronic rejection. Induction immunosuppression has been used as a strategy to reduce early ACR. Recently, our LT program changed our primary induction protocol from basiliximab with standard maintenance immunosuppression to alemtuzumab induction with reduced dose maintenance immunosuppression. The objective of this study was to compare incidence of ACR after this change in the first 6 months after transplantation. METHODS: A retrospective, cohort review of patients 18 years or older, which received their first LT between January 2010 and September 2012. RESULTS: The primary outcome was comparison of average lung biopsy scores at 6 months. Secondary outcomes included development of grade A2 or higher rejection, infectious outcomes, overall graft and patient survival. At 6 months, the average biopsy score was significantly lower in the alemtuzumab group than the basiliximab group (0.12 ± 0.29 vs 0.74 ± 0.67; P < 0.0001) (Table 2). Grade 2 or higher rejection was significantly higher in the basiliximab group (P < 0.0001). CONCLUSIONS: Alemtuzumab provided superior outcomes in regard to average biopsy score and lower incidence of grade 2 or higher rejection at 6 months. There were no differences in infectious complications or overall graft or patient survival between the 2 groups.

Acute cardiovascular effects of firefighting and active cooling during rehabilitation.

OBJECTIVES: To determine the cardiovascular and hemostatic effects of fire suppression and postexposure active cooling. METHODS: Forty-four firefighters were evaluated before and after a 12-minute live-fire drill. Next, 50 firefighters performing the same drill were randomized to undergo postfire forearm immersion in 10 °C water or standard rehabilitation. RESULTS: In the first study, heart rate and core body temperature increased and serum C-reactive protein decreased but there were no significant changes in fibrinogen, sE-selectin, or sL-selectin. The second study demonstrated an increase in blood coagulability, leukocyte count, factors VIII and X, cortisol, and glucose, and a decrease in plasminogen and sP-selectin. Active cooling reduced mean core temperature, heart rate, and leukocyte count. CONCLUSIONS: Live-fire exposure increased core temperature, heart rate, coagulability, and leukocyte count; all except coagulability were reduced by active cooling.

Transplant-related immunosuppression: a review of immunosuppression and pulmonary infections.

Solid organ and hematopoietic stem cell transplantation are definitive therapies for a variety of end-stage diseases. Immunosuppression has improved graft survival but leaves the patient susceptible to infectious complications. Of these, pulmonary infections are the leading cause of morbidity and mortality in the transplant recipient. Allograft rejection is mediated primarily by T cells, with B cells playing a role via antibody production. Depending on the transplant type, rejection can be hyperacute, acute, or chronic. Hyperacute rejection occurs as an immediate response to preformed antibodies to donor human leukocyte antigens. Acute cellular rejection involves recipient T-cell recognition of human leukocyte antigen molecules expressed on donor-derived, antigen-presenting cells (direct allorecognition) or presentation of donor-derived peptides by recipient antigen-presenting cells to recipient T cells (indirect allorecognition). Once the alloantigens are recognized as foreign, the activation, proliferation, and production of cytokines by T lymphocytes and other immune cells lead to the amplification of the alloimmune response. This complex process involves the generation of effector T cells, antibody production by activated B cells, and macrophage activation. Alloimmunity is facilitated by the production of many cytokines, chemokines, and other effector molecules, such as complement. The immunosuppressants involve many classes of drugs, including antibody therapies that eliminate specific groups of cells or alter signaling pathways used by effector cells. The article reviews the agents and associated infections.