Plates were washed with ELISA wash buffer (PBS-1.05% Tween-100mM NaCL-0.5mM NaH2 PO4 -1.5mM Na2HPO4), blocked with 1% bovine serum albumin PBS, incubated with immune sera overnight at 40C, and then washed with ELISA wash buffer. anti-PspA, anti-PspC, anti-PcpA, and anti-PLY antibody levels between asthmatics and non-asthmatics. Th2-immune profile was inversely correlated with anti-PspC antibody levels (r= 0.53, p=0.003). This correlation was significantly modified by asthma status (r= 0.74, p=0.001 for asthmatics vs. r= 0.06, p=0.83 for non-asthmatics). Other pneumococcal protein antibodies Pexmetinib (ARRY-614) were not correlated with Th2-immune profile. == Conclusion == No significant differences in anti-pneumococcal protein antigen antibody levels between asthmatics and non-asthmatics were found. Asthma status is an important effect modifier determining the negative influence of Th2-immune profile on anti-PspC antibody levels. Keywords:Asthma, Atopy, Risk, Humoral immunity, and Pneumococcal virulence proteins == Introduction == Streptococcus pneumoniaeis a leading cause of bacterial pneumonia, meningitis, and sepsis in children worldwide, and it continues to present a major public threat associated with significant morbidity and mortality. In 2000, there was an estimated 14.5 million episodes of serious pneumococcal disease. Worldwide, pneumococcal disease causes more than 800,000 deaths each year among children under age 5 years [1]. Overall, yearly child deaths attributed toS pneumoniaerange from 700,000 to 1 1 million worldwide[2]. In the U.S., pneumococcal diseases were responsible for 4 million illness episodes, 445,000 hospitalizations, and 22,000 fatal cases caused byS. pneumoniaehave been reported in 2004.[3,4] Our previous study suggested that individuals with asthma have a significantly increased risk of serious pneumococcal diseases (pneumococcal pneumonia and/or invasive pneumococcal disease) compared to those without asthma [5]. These results Pexmetinib (ARRY-614) confirmed similar study findings reported by Talbot et al [6]. Thus, the Advisory Committee on Immunization Practices (ACIP) issued a recommendation for all adults with asthma to receive 23-valent pneumococcal polysaccharide vaccine (PPV23) for the prevention of invasive pneumococcal disease (IPD)[7]. Little is known about Pexmetinib (ARRY-614) the mechanisms underlying the higher risk of serious pneumococcal diseases in individuals with asthma. Several studies have identified impaired innate immune function in bronchial epithelial cells among asthmatics [811]. Other studies suggest asthma or its-associated Th2 immune environment Rabbit Polyclonal to Cortactin (phospho-Tyr466) might result in suboptimal adaptive immune function. [1215] We recently reported that T-helper 2 (Th2)-predominant immune responses (e.g., IL-4) to OVA sensitization was a significant risk factor for pneumococcal pneumonia, and Khan et al.[16] reported an association between Th2 cytokines and suppressed anti-pneumococcal antibody responses[17]. In our previous work we found significantly lower serotype-specific antibody to 23 pneumococcal polysaccharide antigens among individuals with asthma compared to those without [18]. This Pexmetinib (ARRY-614) was true for vaccine serotypes for heptavalent pneumococcal conjugate vaccine (PCV-7). These results suggest that the underlying Th-2-immune environment seen in asthma may promote suboptimal humoral immune function, especially T-cell independent type II immunity against pneumococcal polysaccharide (T cells help maturation of antibody response). However, it is unknown whether this is true for humoral immune responses against pneumococcal surface or cytosolic (virulence) protein antigens (i.e., T-cell dependent immune response, which are known to elicit protective immunity for pneumococcal infections)[1925]. To address whether a Th2-immune environment affects humoral immune response to pneumococcal protein antigens, and also whether asthma is associated with a differential immune response to pneumococcal protein antigens, we conducted a cross-sectional study to compare anti-pneumococcal protein antigen antibodies between asthmatics and non-asthmatics and to determine the correlation between Th2 immune profile and humoral immune responses to pneumococcal protein antigens. == Materials and Methods == == Study Design == This was a cross-sectional study examining the correlation between Th2 immune profile (predictor variable) and pneumococcal protein antigen antibody levels (response variable). We also compared pneumococcal protein antigen antibody levels between asthmatics and non-asthmatics. Asthma status was assessed using predetermined criteria delineated inTable 1. Th2 immune profile was assessed using cytokine secretion patterns after PBMC stimulation with dust mite.