title: The safety and efficacy of sublingual and oral immunotherapy for milk allergy.
abstract: BACKGROUND
  Oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) are potential therapies for food allergy, but the optimal method of administration, mechanism of action, and duration of response remain unknown.
  
  
  OBJECTIVE
  We sought to explore the safety and efficacy of OIT and SLIT for the treatment of cow's milk (CM) allergy.
  
  
  METHODS
  We randomized children with CM allergy to SLIT alone or SLIT followed by OIT. After screening double-blind, placebo-controlled food challenges and initial SLIT escalation, subjects either continued SLIT escalation to 7 mg daily or began OIT to either 1000 mg (the OITB group) or 2000 mg (the OITA group) of milk protein. They were challenged with 8 g of milk protein after 12 and 60 weeks of maintenance. If they passed the 60-week challenge, therapy was withdrawn, with challenges repeated 1 and 6 weeks later. Mechanistic correlates included end point titration skin prick testing and measurement of CM-specific IgE and IgG(4) levels, basophil histamine release, constitutive CD63 expression, CD203c expression, and intracellular spleen tyrosine kinase levels.
  
  
  RESULTS
  Thirty subjects with CM allergy aged 6 to 17 years were enrolled. After therapy, 1 of 10 subjects in the SLIT group, 6 of 10 subjects in the SLIT/OITB group, and 8 of 10 subjects in the OITA group passed the 8-g challenge (P = .002, SLIT vs OIT). After avoidance, 6 of 15 subjects (3 of 6 subjects in the OITB group and 3 of 8 subjects in the OITA group) regained reactivity, 2 after only 1 week. Although the overall reaction rate was similar, systemic reactions were more common during OIT than during SLIT. By the end of therapy, titrated CM skin prick test results and CD63 and CD203c expression decreased and CM-specific IgG(4) levels increased in all groups, whereas CM-specific IgE and spontaneous histamine release values decreased in only the OIT group.
  
  
  CONCLUSIONS
  OIT was more efficacious for desensitization to CM than SLIT alone but was accompanied by more systemic side effects. Clinical desensitization was lost in some cases within 1 week off therapy.
authors: Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ckeet1@jhmi.edu
authors: Corinne A
authors: CA
authors: Keet
authors: Pamela A
authors: PA
authors: Frischmeyer-Guerrerio
authors: Ananth
authors: A
authors: Thyagarajan
authors: John T
authors: JT
authors: Schroeder
authors: Robert G
authors: RG
authors: Hamilton
authors: Stephen
authors: S
authors: Boden
authors: Pamela
authors: P
authors: Steele
authors: Sarah
authors: S
authors: Driggers
authors: A Wesley
authors: AW
authors: Burks
authors: Robert A
authors: RA
authors: Wood
mesh_terms: D000284:Administration, Oral; D000286:Administration, Sublingual; D000293:Adolescent; D001491:Basophils / Q000276:immunology; D002648:Child; D003888:Desensitization, Immunologic; D004311:Double-Blind Method; D005260:Female; D006632:Histamine / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology; D008297:Male; D016269:Milk Hypersensitivity / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008894:Milk Proteins / Q000008:administration & dosage*; D010727:Phosphoric Diester Hydrolases / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D011755:Pyrophosphatases / Q000276:immunology; D012074:Remission Induction; D012882:Skin Tests; D000072377:Syk Kinase; D060149:Tetraspanin 30 / Q000276:immunology
chemical_list: C427944:ENPP3 protein, human; D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D060149:Tetraspanin 30; D007073:Immunoglobulin E; D006632:Histamine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases