Context Perfluorinated compounds (PFCs) have emerged as important food contaminants. They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood. Objective To determine whether PFC exposure is associated with antibody response to childhood vaccinations. Design, Setting, and Participants Prospective study of a birth cohort from the National Hospital in the Faroe Islands. A total of 656 consecutive singleton births were recruited during 1997-2000, and 587 participated in follow-up through 2008. Main Outcome Measures Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years. Results Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA). Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of −39% (95% CI, −55% to −17%) in the diphtheria antibody concentration. PFCs in the child’s serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant. In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of −49% (95% CI, −67% to −23%) in the overall antibody concentration. A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 2.38 (95% CI, 0.89 to 6.35) and 4.20 (95% CI, 1.54 to 11.44) for falling below a clinically protective level of 0.1 IU/mL for tetanus and diphtheria antibodies at age 7 years. Conclusion Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.

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Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in longterm follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies. (Blood. 2008;111: 439-445)

BackgroundDevelopmental exposure to polychlorinated biphenyls (PCBs) has been implicated as a possible cause of deficient immune function in children. This study was designed to assess whether prenatal and postnatal exposure to PCBs impacts on antibody response to childhood immunizations.Methods and FindingsTwo birth cohorts were formed in the Faroe Islands, where exposures vary widely, because traditional diets may include whale blubber contaminated with PCBs. Prenatal exposure was determined from maternal concentrations of PCBs in pregnancy serum and milk. Following routine childhood vaccinations against tetanus and diphtheria, 119 children were examined at 18 mo and 129 children at 7 y of age, and their serum samples were analyzed for tetanus and diphtheria toxoid antibodies and for PCBs. The antibody response to diphtheria toxoid decreased at age 18 mo by 24.4% (95% confidence interval [CI], 1.63–41.9; p = 0.04) for each doubling of the cumulative PCB exposure at the time of examination. The diphtheria response was lower at age 7 y and was not associated with the exposure. However, the tetanus toxoid antibody response was affected mainly at age 7 y, decreasing by 16.5% (95% CI, 1.51–29.3; p = 0.03) for each doubling of the prenatal exposure. Structural equation analysis showed that the early postnatal exposure was the most important predictor of a decreased vaccination response.ConclusionsIncreased perinatal exposure to PCBs may adversely impact on immune responses to childhood vaccinations. The clinical implications of insufficient antibody production emphasize the need for prevention of immunotoxicant exposures.

Forty patients with cystic fibrosis and chronic broncho-pulmonary Pseudomonas aeruginosa infection entered a prospective double-blind placebo-controlled study of colistin inhalation. Active treatment consisted of inhalation of colistin one million units twice daily for three months and was compared to placebo inhalations of isotonic saline. Significantly more patients in the colistin inhalation group completed the study as compared to the placebo group (18 versus 11). Colistin treatment was superior to placebo treatment in terms of a significantly better clinical symptom score, maintenance of pulmonary function and inflammatory parameters. We recommend colistin inhalation therapy for cystic fibrosis patients with chronic P. aeruginosa lung infection as a supplementary treatment to frequent courses of intravenous anti-pseudomonas chemotherapy.