02719nam a2200277   4500001000800000005001700008007000300025008004100028040000800069041000800077100003000085245008300115300002500198520188300223650001202106650002602118650001302144650002402157650003902181700001802220700003502238700002102273700002002294700002402314773010302338ESSALUD20260805113858.0ta      t        pe ||||| |||| 00| 0 spa d  aBMG  aeng  aGharahdaghi, Nima eAutor  aInterleukin-10 autoantibodies and HLA-DRB1*01:03 in inflammatory bowel disease  apáginas: 2212-2222  aBackground: Neutralizing autoantibodies against interleukin-10 can result in a phenocopy of monogenic defects of interleukin-10 signaling in children and may be associated with inflammatory bowel disease (IBD). The allele HLA-DRB1*01:03 is the strongest genetic risk factor for ulcerative colitis.
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.
  aALERGIA  aENFERMEDAD AUTOINMUNE  aGENETICA  aGASTROENTEROLOGÍA  aENFERMEDAD INFLAMATORIA INTESTINAL  aYeh, Pai-Jui   aCerón-Gutiérrez, Lourdes    aGriffin, Helen    aGordon, Hannah   aJayamanne,  Chamara0 022717dMassachusetts NEJM GroupoNEJM008tThe New England Journal of Medicine wESSALUDx0028-4793