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Case Reports
. 2017 May;139(5):1698-1701.
doi: 10.1016/j.jaci.2016.10.022. Epub 2016 Nov 19.

Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition

Scott W Canna  1 , Charlotte Girard  2 , Louise Malle  3 , Adriana de Jesus  3 , Neil Romberg  4 , Judith Kelsen  4 , Lea F Surrey  4 , Pierre Russo  4 , Andrew Sleight  5 , Eduardo Schiffrin  5 , Cem Gabay  2 , Raphaela Goldbach-Mansky  3 , Edward M Behrens  4
Affiliations
Case Reports

Life-threatening NLRC4-associated hyperinflammation successfully treated with IL-18 inhibition

Scott W Canna et al. J Allergy Clin Immunol. 2017 May.

Abstract

NLRC4-inflammasome hyperactivity causes infantile-onset Macrophage Activation Syndrome and enterocolitis with extraordinary serum IL-18 elevation (NLRC4-MAS). Herein, we report a critically ill infant with severe, refractory NLRC4-MAS who showed sustained response to treatment with experimental IL-18 inhibition.

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Figures

Fig 1
Fig 1. Rash, enterocolitis, and clinical course in NLRC4-related autoinflammation
(A) erythrodermal skin lesions. (B) Ulcerative duodenal plaques. (C) Edematous sigmoid colon with flattened villi, crypt drop-out, and apoptotic crypt epithelial cells (inset circles); 20×, H&E. (D) C-reactive protein (CRP), ferritin, enteral intake, and anti-inflammatory medications. Red box: MAS onset. Red line: start of rhIL-18bp. *Steroid (gray outline): running seven-day average of daily prednisone-equivalent dose.
Fig 2
Fig 2. Serum, Stool, and Transcriptional Analyses
Serum (A) and stool (B) cytokines (in pg/mL) and serum ferritin (gray, ng/mL). Upper limit of healthy controls, if visible, crosses y-axis. (C) and (D) Whole blood RNA-seq comparing flare versus post-treatment in this patient (V341A), another NLRC4-MAS patient (T337S)(2), and seven NOMID patients. Log10 fold-change for genes higher (red) or lower (blue) during flare in both NLRC4-MAS patients. See also Supplemental Table 1. (D) Most-enriched transcriptional network generated by the differentially-expressed gene list. *Upper Limit of detection.
See this image and copyright information in PMC

Comment in

  • IL-18 binding protein reverses the life-threatening hyperinflammation of a baby with the NLRC4 mutation.
    Novick D, Dinarello CA. Novick D, et al. J Allergy Clin Immunol. 2017 Jul;140(1):316. doi: 10.1016/j.jaci.2017.02.037. Epub 2017 Apr 28. J Allergy Clin Immunol. 2017. PMID: 28457594 No abstract available.
  • Reply.
    Canna SW, Girard C, Malle L, de Jesus A, Romberg N, Kelsen J, Surrey LF, Russo P, Sleight A, Schiffrin E, Gabay C, Goldbach-Mansky R, Behrens EM. Canna SW, et al. J Allergy Clin Immunol. 2017 Jul;140(1):316-317. doi: 10.1016/j.jaci.2017.03.016. Epub 2017 Apr 29. J Allergy Clin Immunol. 2017. PMID: 28460789 No abstract available.

References

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