Abnormal neutrophil chemotactic activity in children with congenital insensitivity to pain with anhidrosis (CIPA): the role of nerve growth factor

Clin Immunol. 2009 Mar;130(3):365-72. doi: 10.1016/j.clim.2008.09.005. Epub 2008 Oct 26.


A 1926-ins-T mutation in the TrkA gene encoding the tyrosine kinase receptor for nerve growth factor (NGF) was previously documented in patients with congenital insensitivity to pain with anhidrosis (CIPA). These patients suffer from skin lacerations which often evolve into deep tissue infections. Abnormality in neutrophil functions may explain this high rate of severe infections. In this study we show that chemotaxis was significantly (P<0.001) suppressed in patients' neutrophils, compared to healthy controls. Although NGF alone did not exert a chemotactic effect, its presence enhanced both migration toward fMLP and phosphorylation of MAP kinases (ERK and JNK) in neutrophils from healthy controls, but not in neutrophils from CIPA patients. The significantly impaired chemotactic activity of neutrophils from a CIPA patient, which has been attributed to the molecular defect in the TrkA receptor, may contribute to the high rate of infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chemokines / metabolism
  • Chemotaxis / drug effects
  • Child
  • Child, Preschool
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • Hypohidrosis / complications*
  • Infant
  • MAP Kinase Kinase 4 / metabolism
  • Male
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nerve Growth Factor / metabolism*
  • Nerve Growth Factor / pharmacology
  • Neutrophils / metabolism*
  • Pain Insensitivity, Congenital / complications*
  • Pain Insensitivity, Congenital / immunology
  • Pain Insensitivity, Congenital / physiopathology*
  • Young Adult


  • Chemokines
  • Nerve Growth Factor
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 4