NF-κB dysfunction resulting from NEMO (NF-kappaB essential modulator) mutation can lead to significant alterations in cytokine production. However, little is known about changes in the expression of downstream molecules in patients with incontinentia pigmenti (IP). We aim to investigate serial cytokine expressions during the first 2 years of life in young infants with IP, the period in which skin inflammation and morphological changes are most significant. Gene analysis and X-inactivation test were performed for the two neonates with IP. Peripheral mononuclear cells were obtained after birth and successively at 6-month interval up to the age of two years. Levels of TNF-α and IL-6 were analyzed with ELISA before and after stimulating with Toll-like receptor ligands. The result showed the male IP patient had normal NEMO allele. His cytokine level, although initially lower, had returned to a level comparable with those of controls at 12 months of age. The female infant had mutated NEMO gene. Her baseline TNF-α level was significantly higher than those of the control subjects at birth and remained high by 6 months of age. All cytokine responses had decreased significantly by 2 years of age, the time in which all vesicular skin lesions had resolved. Both infants had normal serum immunoglobulin level and remained infection free during the follow up period. To our knowledge, this is the first report that demonstrates serial changes of cytokine profiles in humans with IP. This study showed that in the presence of NEMO mutation, alteration of cytokine production was remarkable during the first year of life, which may account for the prominent inflammatory changes in skin morphology.
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