Injury stimulates an innate respiratory immunoglobulin a immune response in humans

BACKGROUND: Secretory immunoglobulin A (SIgA) is the specific immune antibacterial defense. Since pneumonia frequently complicates the course of trauma patients, we studied early airway immune responses after injury. METHODS: Twelve severely injured, intubated (expected for >/=5 d) patients had tracheal and bilateral lung lavage (BAL) within 30 hours of injury (n = 12). Epithelial lining fluid (ELF) volume and SIgA were measured by urea dilution and enzyme-linked immunosorbent assay (ELISA), respectively. Control BAL specimens were obtained from eight healthy elective surgical patients. Anatomically based comparisons were made between groups with Welch's unpaired t test. To verify human data, 30 male mice received no injury (time 0, n = 7) or injury with abdominal and neck incisions and were killed for airway IgA at 4 (n = 7), 8 (n = 8), and 24 (n = 8) hours. Analysis of variance (ANOVA) and Fisher's protected least significant difference testing was used to analyze animal data. RESULTS: Initial trauma patient SIgA concentration (SIgA/mL ELF) increased compared with control in the lungs bilaterally (p < 0.05 both right and left). ELF volume was significantly higher in the right lung (p = 0.02) and just missed statistical significance (p = 0.07) on the left. Mouse IgA increased 8 hours after stress (p < 0.05 versus 0, 4, and 24 hours) and returned to normal by 24 hours. CONCLUSION: A previously unrecognized innate human airway mucosal immune response with increased airway SIgA and ELF occurs after severe injury and is reproducible experimentally. This accessible, quantifiable human response allows study of clinical strategies to reduce infections via mucosal immune therapies

Temporary And Durable Mechanical Circulatory Support For Single Ventricular Failure in an Adult

Patients palliated with Fontan circulation requiring mechanical circulatory support pose anatomic and physiologic challenges. We treated a Fontan patient with acute ventricular failure with sequential temporary and durable support devices. Aspects of treatment with each device required modification based on the patient’s anatomy and physiology

Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis

Infection by Plasmodium parasites has been a major cause of mortality and morbidity in humans for thousands of years. Despite the considerable reduction of deaths, according to the WHO, over 5 billion people are still at risk, with about 216 million worldwide cases occurring in 2016. More compelling, 15 countries in sub-Saharan Africa bore 80% of the worldwide malaria burden. Complete eradication has been challenging, and the development of an affordable and effective vaccine will go a long way in achieving elimination. However, identifying vaccine candidate targets has been difficult. In the present study, we use a highly effective immunization protocol that confers long-lasting sterile immunity in combination with a whole P. falciparum proteome microarray to identify antibody responses associated with protection. This study characterizes a novel antibody profile associated with sterile protective immunity and trimodal humoral responses that sheds light on the possible mechanism of CPS-induced immunity against P. falciparum parasites.Immunization with sporozoites under chloroquine chemoprophylaxis (CPS) induces distinctly preerythrocytic and long-lasting sterile protection against homologous controlled human malaria infection (CHMI). To identify possible humoral immune correlates of protection, plasma samples were collected from 38 CPS-immunized Dutch volunteers for analysis using a whole Plasmodium falciparum proteome microarray with 7,455 full-length or segmented protein features displaying about 91% of the total P. falciparum proteome. We identified 548 reactive antigens representing 483 unique proteins. Using the breadth of antibody responses for each subject in a mixture-model algorithm, we observed a trimodal pattern, with distinct groups of 16 low responders, 19 medium responders, and 3 high responders. Fifteen out of 16 low responders, 12 of the 19 medium responders, and 3 out of 3 high responders were fully protected from a challenge infection. In the medium-responder group, we identified six novel antigens associated with protection (area under the curve [AUC] value of ≥0.75; P < 0.05) and six other antigens that were specifically increased in nonprotected volunteers (AUC value of ≤0.25; P < 0.05). When used in combination, the multiantigen classifier predicts CPS-induced protective efficacy with 83% sensitivity and 88% specificity. The antibody response patterns characterized in this study represent surrogate markers that may provide rational guidance for clinical vaccine development