Interleukin-10 Autoantibodies and HLA-DRB1*01:03 in Inflammatory Bowel Disease.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Gharahdaghi Nima, Yeh Pai-Jui, Ceron-Gutierrez Lourdes, Griffin Helen, Gordon Hannah, Jayamanne Chamara, Fracchia Alice, Chong Amanda Y, Walsh Alissa, Brain Oliver, Baker Katherine, Kockelbergh Hannah, Luo Yang, Guevara Becerra Martha, Vadakethala Katherine, Coy Madeleine, Kabiri Ladan, Barnardo Martin, Dunachie Susanna, Kronsteiner Barbara, Adams Anna, Fowler Darren, Zhang Qian, Fachal Laura, Anderson Carl A, Desoki Rofaida, Vestergaard Marie Vibeke, Larsen Lone, Wyatt Nicola J, Lees Robert D, Mulligan Robert J, Dong Chaonan, Sharip Mohmmed Tauseef, Faustini Siân E, Shields Adrian, Pakpoor Julia, Naz Bushra, Richter Alex, Satsangi Jack, Lamb Christopher A, Parkes Miles, Powrie Fiona, Mentzer Alexander J, Sazonovs Aleksejs, Jess Tine, Klenerman Paul, Travis Simon, Hambleton Sophie, Doffinger Rainer, Uhlig Holm H
Аннотация
METHODS: We used a cellular interleukin-10 reporter assay and a confirmatory competitive enzyme-linked immunosorbent assay to assess neutralizing interleukin-10 autoantibodies in serum samples obtained from patients with IBD in the Oxford and U.K. IBD BioResource cohorts and from persons without IBD (controls). An in vitro cytokine-release bioassay was performed in a subgroup of patients to assess interleukin-10, interleukin-23, interleukin-1β, tumor necrosis factor, and interleukin-6. We performed HLA association analysis using imputation and high-resolution sequencing.
RESULTS: Interleukin-10-neutralizing autoantibodies were detected in 173 of 4909 patients with IBD (3.5%; 95% confidence interval [CI], 3.0 to 4.1) and in none of 1006 controls (P<0.001). High anti-interleukin-10 activity in serum was associated with a reduction in detectable interleukin-10 and with an exaggerated proinflammatory cytokine response, consistent with functional neutralization of interleukin-10 signaling. Anti-interleukin-10 seropositivity was strongly associated with HLA-DRB1*01:03 on the basis of imputed data from the Oxford cohort (odds ratio, 50.0; 95% CI, 16.4 to 152.3; P = 6.14×10-12) and the U.K. IBD BioResource cohort (odds ratio, 24.7; 95% CI, 14.5 to 42.1; P = 6.20×10-32) and in a high-resolution sequencing analysis of data from the Oxford cohort (odds ratio, 29.5; 95% CI, 12.2 to 71.1; P = 4.85×10-14).
CONCLUSIONS: Neutralizing interleukin-10 autoantibodies were present in a subgroup of patients with IBD and were strongly associated with HLA-DRB1*01:03. (Funded by the National Institute for Health and Care Research and others.).