Levels of soluble human leukocyte antigen-G are increased in asthmatic airways

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To the Editors: Human leukocyte antigen-G (HLA-G) is a non-classical, class Ib, major histocompatibility complex antigen, encoded by a gene on chromosome 6p21 within the HLA complex 1. HLA-G is constitutively expressed during pregnancy where it has a critical role in maintaining immune tolerance toward the allogenic fetus and placenta 2, 3, but has also been associated with inflammatory diseases such as psoriasis, multiple sclerosis, and ulcerative colitis, and with solid-organ transplantation 3, 4. We recently reported associations between variation in HLA-G and risk for asthma in Chicago-area asthma families, in multigenerational Dutch asthma families and in a birth cohort at high risk for developing asthma 1, 5. A role for HLA-G in asthma pathogenesis was further suggested by the demonstration of expression of a soluble isoform of HLA-G, sHLA-G5, in airway epithelial cells 1 and of increased circulating plasma levels of sHLA-G in children with atopic asthma 6. Because airway inflammation in asthma involves a T-helper cell (Th) type 2-skewing of lymphocytes similar to pregnancy, HLA-G is an attractive candidate molecule for promoting the immune profile characteristic of asthma. Localisation of HLA-G to airway epithelium suggests that its dysregulation could contribute to airway inflammation in chronic asthma. To evaluate this further, we hypothesised that HLA-G abundance would be increased in asthmatic airways. To test this hypothesis, we measured concentrations of sHLA-G in bronchoalveolar lavage (BAL) fluid obtained from 12 non-asthmatic control subjects and 15 subjects with mild persistent asthma. The use of human subjects was approved by the University of Chicago Institutional Review Board (Chicago, IL, USA). Asthma was diagnosed using National Asthma Education and Prevention Program guidelines. …