Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1.

Abstract

A patient with leukocyte adhesion deficiency type 1 (LAD1) had severe periodontitis and an intractable, deep, nonhealing sacral wound. We had previously found a dominant interleukin-23-interleukin-17 signature at inflamed sites in humans with LAD1 and in mouse models of the disorder. Blockade of this pathway in mouse models has resulted in resolution of the immunopathologic condition. We treated our patient with ustekinumab, an antibody that binds the p40 subunit of interleukin-23 and interleukin-12 and thereby blocks the activity of these cytokines, inhibiting interleukin-23-dependent production of interleukin-17. After 1 year of therapy, our patient had resolution of his inflammatory lesions without serious infections or adverse reactions. Inhibition of interleukin-23 and interleukin-17 may have a role in the management of LAD1. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

• Authors: Niki M Moutsopoulos, Christa S Zerbe, Teresa Wild, Nicolas Dutzan, Laurie Brenchley, Giovanni DiPasquale, Gulbu Uzel, Karen C Axelrod, Andrea Lisco, Lucia D Notarangelo, George Hajishengallis, Luigi D Notarangelo, Steven M Holland
• Journal: The New England journal of medicine (N Engl J Med) Vol. 376 Issue 12 Pg. 1141-1146 (03 23 2017) ISSN: 1533-4406 [Electronic] United States
• PMID: 28328326 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-17
• Interleukin-23
• RNA, Messenger
• Interleukin-12
• Ustekinumab

Topics

• Gingiva (pathology)
• Humans
• Injections, Subcutaneous
• Interleukin-12 (antagonists & inhibitors)
• Interleukin-17 (metabolism)
• Interleukin-23 (antagonists & inhibitors, metabolism)
• Leukocyte-Adhesion Deficiency Syndrome (complications, drug therapy)
• Male
• Periodontal Diseases (drug therapy, etiology, pathology)
• RNA, Messenger (metabolism)
• Skin Ulcer (drug therapy, etiology, pathology)
• Ustekinumab (adverse effects, therapeutic use)
• Young Adult