Immunoglobulin is found to exert its effect through modulation of expression and function of FcR, interference with complement activation and the cytokine network.40 Antibodies in immunoglobulin products recognize and neutralize idiotypes of disease-associated and natural autoantibodies as well as B-cell antigen receptors. In this article, we provide a review of the current knowledge on immunoglobulin treatment in patients with COPD and discuss plausible mechanisms as to how immunoglobulin treatment may work to reduce AECOPD frequency. Keywords: chronic obstructive pulmonary disease, immunoglobulin treatment, exacerbation Introduction Chronic Obstructive Pulmonary Disease (COPD) is usually a burdensome illness associated with significant morbidity and mortality. Some individuals with COPD experience recurrent acute exacerbations (AECOPD), which UNC 926 hydrochloride are events characterized by a worsening of respiratory symptoms that are beyond normal day-to-day variation and lead to a change in medication and/or healthcare services.1 AECOPD accelerate disease progression and are the major cause of emergency department visits and hospitalizations.2,3 Current strategies to prevent and reduce AECOPD frequency include pharmacotherapy, patient vaccination and general self-management education.4 However, the efficacy of this approach is moderate at best and it is clear that a targeted and more effective prevention strategy is needed.?needed.Table Table 1 Summary of Study Characteristics and Study Outcomes in mice.31 It is therefore possible that parenteral administration of IgG increases IgG concentrations in the luminal airway, which enhances mucosal immunity. An improved mucosal immunity by this mechanism may reduce the risk of respiratory infections, and hence reduce the risk of AECOPD in COPD patients. Reestablishment of Healthy Lung Microbiome and Reduction of Airway Inflammation Healthy lungs contain resident commensal microbes that colonize the lining of the respiratory tract, reminiscent to what has been reported for the gastrointestinal tract. The most common bacterial genera in the lower airway among healthy individuals are Prevotella, Veillonella, and Streptococcus.32 On the other hand, pathogenic bacteria such as Haemophilus UNC 926 hydrochloride influenzae, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and Moraxella catarrhalis33,34 are predominant in the diseased lungs of patients with COPD. Microbial components and their metabolites have the potential to maintain immune homeostasis in the host. For example, commensal neomycin-sensitive bacteria regulate protective immune responses in the lungs against influenza A virus infections. They do so by generating virus-specific CD4 and CD8 T cells through inflammasome activation and dendritic cell UNC 926 hydrochloride migration from the site of contamination to lymph nodes. Disruption of composition or the number of microbiota termed dysbiosis may contribute to the development, progression, or exacerbation of various inflammatory disorders of the lungs, including asthma, COPD and cystic fibrosis.35 Pathogenic bacteria can increase airway inflammation by stimulating production of inflammatory cytokines34,36 and by degrading IgA.37 We hypothesize that immunoglobulin treatment may reset dysbiosis by reducing pathogenic microbes which can result in decreased airway inflammation. Given that AECOPD is usually characterized by heightened airway inflammation, it Rabbit Polyclonal to NARG1 is indeed plausible that improved respiratory microbiome composition may reduce AECOPD frequency. Reduction of Autoantibodies in the Airways Over the past decade, there has been an increasing body of evidence linking autoimmunity and COPD. 38 Although it has not been clearly established, serum and sputum autoantibodies (antibodies against self-antigens) may correlate with a certain COPD phenotype such as those with recurrent AECOPD.39 Immunoglobulin treatment UNC 926 hydrochloride has been used successfully to treat many immune-mediated diseases caused by autoreactive B lymphocytes. Immunoglobulin is found to exert its effect through modulation of expression and function of FcR, interference with complement activation and the cytokine network.40 Antibodies in immunoglobulin products recognize and neutralize idiotypes of disease-associated and natural autoantibodies as well as B-cell antigen receptors. Reduction in the autoantibody titer in vivo has been observed in several conditions following immunoglobulin treatment.41,42 Thus, it could be suggested that immunoglobulin may reduce AECOPD by interfering with the production or effect of autoantibodies in the airways. However, immunoglobulin dosage required for the treatment of autoimmune conditions is generally higher than the dosage used in the treatment for immunodeficient patients. We and others observed a reduction in AECOPD using the standard dosage recommended for immunodeficiency.7,8 In other words, the higher immunoglobulin dosage required for the treatment of autoimmune conditions was not needed to reduce AECOPD frequency in COPD patients. Thus, it seems less likely that immunoglobulin?treatment in.