title: Successful anti-TNF-α treatment in a girl with LAD-1 disease and autoimmune manifestations.
abstract: Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive disorder, caused by the absence or reduced expression of the beta-2 integrins on granulocytes, and characterized by the inability of these cells to emigrate from the bloodstream towards the sites of tissue inflammation. A twelve-year-old girl with a diagnosis of LAD-1 syndrome and recurrent skin and mucosal infections since birth, presented with a two week history of fever, abdominal pain, vomiting, weight loss and polyarthralgia. She underwent an exploratory laparotomy with the finding of inflamed terminal ileum and colon and a normal appendix. Colonoscopy and videocapsule endoscopy showed multiple ileal and colonic mucosal ulcerations, which were compatible with inflammatory bowel disease, confirmed on histological examination. Given the lack of response to conventional therapy (prednisone and mesalamine), a monoclonal anti-TNF-α antibody was started at a dosage of 5 mg/kg at weeks 0,2,4,6 and then every 8 weeks. We observed a significant improvement of all clinical and laboratory parameters after the first weeks of therapy. Five months later, we anticipated the drug's administration every 5 weeks because of a precocious recurrence of symptoms. After 30 months of treatment no relapse nor any relevant side effects have been observed, and corticosteroids were withdrawn. Interestingly, our patient presented a small subset of CD18+ T cells, similarly to previously reported LAD-1 patients with mild phenotype, inflammatory bowel disease and CD18+ somatic revertant T cells. To the best of our knowledge, this is the first LAD-1 pediatric patient with inflammatory autoimmune complications who experienced a positive response to anti-TNF-α treatment.
authors.affiliation: Department of Pediatrics, University of Chieti, Chieti, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Marsili
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.forename: Marta
authors.initials: M
authors.lastname: Lucantoni
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Marzio
authors.forename: Manuela
authors.initials: M
authors.lastname: Baronio
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Vitali
authors.forename: Giuliano
authors.initials: G
authors.lastname: Lombardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Chiarelli
authors.forename: Luciana
authors.initials: L
authors.lastname: Breda
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002465:Cell Movement / Q000235:genetics; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D039641:Integrin beta Chains; D014409:Tumor Necrosis Factor-alpha