The association of ERAP1 with ankylosing spondylitis (AS)1 among HLA-B27-positive individuals suggests that ERAP1 polymorphism may affect pathogenesis by altering peptide-dependent features of the HLA-B27 molecule. Comparisons of HLA-B*27:04-bound peptidomes from cells expressing different natural variants of ERAP1 revealed significant differences in the size, length, and amount of many ligands, as well as in HLA-B27 stability. Peptide analyses suggested that the mechanism of ERAP1/HLA-B27 interaction is a variant-dependent alteration in the balance between epitope generation and destruction determined by the susceptibility of N-terminal flanking and P1 residues to trimming. ERAP1 polymorphism associated with AS susceptibility ensured efficient peptide trimming and high HLA-B27 stability. Protective polymorphism resulted in diminished ERAP1 activity, less efficient trimming, suboptimal HLA-B27 peptidomes, and decreased molecular stability. This study demonstrates that natural ERAP1 polymorphism affects HLA-B27 antigen presentation and stability in vivo and proposes a mechanism for the interaction between these molecules in AS.

No abstract

Understanding the colonization of Pseudomonas aeruginosa (P. aeruginosa) in healthy humans is useful for future prevention and treatment of P. aeruginosa infection. This study aimed to investigate the prevalence and risk factors of of P. aeruginosa colonization in healthy humans. At the same time, the virulence of the isolated P. aeruginosa was also studied. In the study, 609 Vietnamese volunteers (310 females and 299 males, age range of 2 to 73 years), who had no acute infection or disease symptoms participated at the time of sample collection. Samples were taken from the throat, nostrils, and outer ears. P. aeruginosa was found in 19 participants (3.12%, 95% CI: 0.017–0.045), mainly from the throat (11/19, 57.89%). Participants with a history of sinusitis were 11.57 times more likely to be colonized with P. aeruginosa than participants without a history of sinusitis (OR: 11.57, 95% CI: 4.08–32.76, p-value < 0.0001, Fisher’s Exact test). Age and sex were not significantly associated with P. aeruginosa colonization. Among 16 P. aeruginosa isolates used in virulence tests, 100% (16/16) were positive for the synthesis of biofilm, pyocyanin, and siderophores; 93.75% (15/16) isolates were positive for the synthesis of gelatinase and protease; and 50% (8/16) isolates were positive for lipase. There were no differences in the pattern and range of virulence factors of P. aeruginosa isolates taken from participants with and without sinusitis history. P. aeruginosa colonized 3.12% of participants, and its presence was associated with sinusitis history.