Functional studies to understand class II MHC as a gene modifier in cystic fibrosis
| Autor: | Shiping Lu, Kejing Song, Jay K. Kolls |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:145.53-145.53 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.204.supp.145.53 |
| Popis: | Cystic fibrosis (CF) is an inherited life-threatening disease caused by mutated chlorine channel cystic fibrosis transmembrane conductance regulator(CFTR). Around 60% of CF patients have homozygous F508del mutation. Along with chronic bacterial infection, the integrity and function of pulmonary epithelium were compromised. Pseudomonas aeruginosa (P. a) is the most predominant pathogen, leading to decreased lung function and increased mortality in CF patients. So, prevention/eradication of airway P.a colonization is crucial to maintain lung function. Genome-wide association studies revealed human leukocyte antigen class II(HLAII) within the F508del population are associated with the age of P.a colonization and lung disease severity. However, the role of HLA class II in CF progress is not fully defined. We hypothesized that there may exist differences in antibody isotypes, titer, specificity or affinity that influence/determine lung function of CF patients. Therefore, we recruited a cohort of non-progressive F508del CF patients with confirmed P. a colonization but different lung function. Our results showed sera of CF patients have significantly higher specific IgG and IgG1 titers and stronger bacterial surface binding against mucoid P.a compared of non-CF controls. To assess antigen specificity, we performed immunoprecipitation followed by proteomics, that antibodies from CF sera have a common target, outer membrane protein OprI. Besides, CF sera inhibited bacterial biofilm formation time-dependently compared to non-CF serum. Taken together these studies may shed light on the role of HLA class II as a gene modifier in CF. |
| Databáze: | OpenAIRE |
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