Neutrophil chemotaxis in a patient with neonatal-onset multisystem inflammatory disease and Muckle-Wells syndrome.
BACKGROUND
Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, and articular syndrome is an autoinflammatory disease characterized by urticarial rash, arthropathy, and central nervous system inflammation.


OBJECTIVE
To describe a 13-year-old girl with overlapping symptoms of NOMID and Muckle-Wells syndrome who has a mutation in cryopyrin (NALP3).


METHODS
We examined neutrophil migration using transwell assay and time-lapse videomicroscopy. We also examined p38 mitogen-activated protein kinase (MAPK) activation in patient and control neutrophils using Western blot analysis.


RESULTS
Neutrophil defects in chemotactic migration were found to a variety of chemoattractants, including interleukin 8, N-formyl-methionyl-leucyl-phenylalanine, complement C5a, and leukotriene B4. Her neutrophils exhibited elevated basal and stimulated p38 MAPK activation in response to interleukin 8, N-formyl-methionyl-leucyl-phenylalanine, complement C5a, and leukotriene B4.


CONCLUSIONS
This study is the first, to our knowledge, to demonstrate defects in neutrophil chemotaxis and p38 MAPK signaling in a patient with NOMID and Muckle-Wells syndrome and a cryopyrin mutation.
Lokuta
Mary A
MA
Department of Pediatrics, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.
Cooper
Kate M
KM
Aksentijevich
Ivona
I
Kastner
Daniel L
DL
Huttenlocher
Anna
A
D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics; D002634:Chemotaxis, Leukocyte; D015936:Complement C5a / Q000378:metabolism; D010505:Familial Mediterranean Fever / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000235:genetics / Q000276:immunology*; D016209:Interleukin-8 / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D009154:Mutation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002352:Carrier Proteins; D016209:Interleukin-8; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D048051:p38 Mitogen-Activated Protein Kinases