Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1.
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.).
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Niki M
NM
Moutsopoulos
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Christa S
CS
Zerbe
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Teresa
T
Wild
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Nicolas
N
Dutzan
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Laurie
L
Brenchley
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Giovanni
G
DiPasquale
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Gulbu
G
Uzel
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Karen C
KC
Axelrod
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Andrea
A
Lisco
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Lucia D
LD
Notarangelo
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
George
G
Hajishengallis
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Luigi D
LD
Notarangelo
From the National Institute of Dental and Craniofacial Research (N.M.M., T.W., N.D., L.B., G.D.), the Laboratory of Clinical Infectious Diseases (C.S.Z., G.U., S.M.H.), and the Laboratory of Immunoregulation (A.L.), National Institute of Allergy and Infectious Diseases, and the Wound-Ostomy Care Nursing Service, Clinical Center (K.C.A.) - all at the National Institutes of Health, Bethesda, MD; the Pediatric Onco-Hematology and Bone Marrow Transplantation Unit, Children's Hospital, Spedali Civili of Brescia, Brescia, Italy (Lucia D. Notarangelo); the Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia (G.H.); and the Division of Immunology, Boston Children's Hospital and Harvard Medical School, Boston (Luigi D. Notarangelo).
Steven M
SM
Holland
D005881:Gingiva / Q000473:pathology; D006801:Humans; D007279:Injections, Subcutaneous; D018664:Interleukin-12 / Q000037:antagonists & inhibitors*; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000150:complications / Q000188:drug therapy*; D008297:Male; D010510:Periodontal Diseases / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012883:Skin Ulcer / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D000069549:Ustekinumab / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D020381:Interleukin-17; D053759:Interleukin-23; D012333:RNA, Messenger; D018664:Interleukin-12; D000069549:Ustekinumab