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.
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.
Authors: Simon A Hirota; Jeffrey Ng; Alan Lueng; Maitham Khajah; Ken Parhar; Yan Li; Victor Lam; Mireille S Potentier; Kelvin Ng; Misha Bawa; Donna-Marie McCafferty; Kevin P Rioux; Subrata Ghosh; Ramnik J Xavier; Sean P Colgan; Jurg Tschopp; Daniel Muruve; Justin A MacDonald; Paul L Beck Journal: Inflamm Bowel Dis Date: 2010-09-24 Impact factor: 5.325
Authors: Sa Kan Yoo; Pui-Ying Lam; Mark R Eichelberg; Lauren Zasadil; William M Bement; Anna Huttenlocher Journal: J Cell Sci Date: 2012-09-19 Impact factor: 5.285
Authors: Taylor W Starnes; David A Bennin; Xinyu Bing; Jens C Eickhoff; Daniel C Grahf; Jason M Bellak; Christine M Seroogy; Polly J Ferguson; Anna Huttenlocher Journal: Blood Date: 2014-01-13 Impact factor: 22.113
Authors: Paola Galozzi; Ola Negm; Sara Bindoli; Patrick Tighe; Paolo Sfriso; Leonardo Punzi Journal: Int J Mol Sci Date: 2022-02-05 Impact factor: 5.923