KIR and HLA interactions are associated with control of primary CMV infection in solid organ transplant recipients.

Cytomegalovirus (CMV) infection remains a major source of morbidity and mortality in solid organ transplant recipients. Killer immunoglobulin-like receptors(KIR) are genetically polymorphic natural killer(NK) cell receptors important in antiviral responses. A retrospective, single-center cohort study was performed to study the interaction of KIR genotype and primary control of CMV infection after transplantation.Time to first CMV viremia was determined for a cohort of 531 CMV serology donor positive/recipient negative solid organ transplant recipients. Of the KIR genes,KIR2DL3 and KIR2DS2 were most strongly associated with time to CMV viremia in random survival forest analysis. As KIR2DL3 and KIR2DS2 both interact with HLA-C1, these interactions were evaluated. Seventy six recipients were found to be positive for both KIR2DL3 and KIR2DS2 and expressed only HLA-C1 antigens in both recipient and donor. These patients had a substantially reduced hazard of CMV viremia in the first year after solid organ transplantation (hazard ratio 0.44, 95% CI 0.27­0.72, p=0.0012). In KIR2DL3+/KIR2DS2+/HLA-C1/1 recipients who received an organ from a non-C1/1 donor, this protective effect was not observed. These results improve our understanding of human NK cell function in primary CMV infection after transplant.

Human monoclonal antibodies against Pseudomonas aeruginosa lipopolysaccharide derived from transgenic mice containing megabase human immunoglobulin loci are opsonic and protective against fatal pseudomonas sepsis.

Pseudomonas aeruginosa is a significant human pathogen, and no vaccine is commercially available. Passive antibody prophylaxis using monoclonal antibodies (MAb) against protective P. aeruginosa epitopes is an alternative strategy for preventing P. aeruginosa infection, but mouse MAb are not suitable for use in humans. Polyclonal human antibodies from multiple donors have variable antibody titers, and human MAb are difficult to make. We used immunoglobulin-inactivated transgenic mice reconstituted with megabase-size human immunoglobulin loci to generate a human MAb against the polysaccharide (PS) portion of the lipopolysaccharide O side chain of a common pathogenic serogroup of P. aeruginosa, 06ad. The anti-PS human immunoglobulin G2 MAb made from mice immunized with heat-killed P. aeruginosa was specific for serogroup 06ad pseudomonas. The MAb was highly opsonic for the uptake and killing of P. aeruginosa by human polymorphonuclear leukocytes in the presence of human complement. In addition, 25 microg of the MAb protected 100% of neutropenic mice from fatal P. aeruginosa sepsis. DNA sequence analysis of the genes encoding the MAb revealed V(H)3 and Vkappa2/A2 variable-region genes, similar to variable-region genes in humans immunized with bacterial PS and associated with high-avidity anti-PS antibodies. We conclude that human MAb to P. aeruginosa made in these transgenic mice are highly protective and that these mice mimic the antibody response seen in humans immunized with T-cell-independent antigens such as bacterial PS.

Patient priorities with traumatic lacerations.

Clinical trials should use outcomes that are important to patients. We sought to determine the aspects of laceration management that are most important to patients. A prospective observational survey was conducted at one suburban and one urban university ED during November to December 1998 that included ED patients and visitors with and without current or prior lacerations. Trained research assistants approached 747 people of which 724 (97%) completed a 25-item closed question survey that evaluated demographics, prior laceration repairs, and assessed the relative importance of least painful repair, ED length of stay, cosmetic outcome, functional recovery, practitioner compassion, avoidance of wound infection, total costs, and missed days of work or school using a five-item Likert scale (not important-extremely important). Additionally, the relative importance of these items was compared. Data were analyzed with descriptive statistics and 95% confidence intervals (CIs). Seven hundred twenty-four people participated; 383 (53%) had prior lacerations; 92 (14%) had lacerations at the time of the survey. The most important aspect of care for respondents were normal function (28%), avoiding infection (20%), cosmetic outcome (17%), and least painful repair (17%). Based on Likert scale data, most important aspects of care were: avoiding wound infection (mean [95% CI], 4.58 [4.52 to 4.64]), normal function (4.54 [4.48 to 4.6]), cosmetic outcome (3.78 [3.68 to 3.88]), and least painful repair (3.84 [3.76 to 3.92]). Cost, length of stay, missed work/school, and compassion were less important (range, 3.0 to 3.7). Patients with facial lacerations chose cosmetic outcome as the most important aspect of care while all others chose function. Patients prioritize the medical outcomes of laceration repair (function, avoiding infection, cosmesis, pain) more than cost, compassion, ED length of stay and inconvenience (missed work/school). Cosmetic outcome is particularly important to patients with facial lacerations. This information should be useful when designing outcome studies of laceration management.