Serum KL-6 Differentiates Neuroendocrine Cell Hyperplasia of Infancy From the Inborn Errors of Surfactant Metabolism

Minh L Doan ^1*, Okan Elidemir ², Megan K Dishop ³, Haibin Zhang ², E O'brian Smith ², Phil Black ⁴, Robin Deterding ⁵, Dion Roberts ⁶ and Leland L Fan ²

¹ Department of Pediatrics, Tripler Army Medical Center, United States
² Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, United States
³ Department of Pathology, Baylor College of Medicine, Texas Children's Hospital, United States
⁴ Department of Pediatrics, University of Missouri at Kansas City, Children’s Mercy Hospital, United States
⁵ Department of Pediatrics, University of Colorado Health Science Center, Children’s Hospital, United States
⁶ Pediatric Breathing Disorders Clinic, United States

^* To whom correspondence should be addressed. E-mail: minhluan.doan{at}amedd.army.mil.

Accepted 2 February 2009

Abstract

Background: We sought to determine if KL-6 is a useful biomarker in differentiating neuroendocrine cell hyperplasia of infancy (NEHI), a benign form of children’s interstitial lung disease, from the more severe inborn errors of surfactant metabolism (IESM), since their clinical presentation can be similar.

Methods: Serum KL-6 levels were measured in 10 healthy control children, 6 with NEHI and 13 with IESM (4 with surfactant protein C and 9 with ABCA3 mutations). The initial clinical presentation, findings on previous CT scans, and ILD scores at the time of KL-6 testing were compared. Correlations between KL-6 levels with age and with interval from lung biopsy were evaluated.

Results: The median (range) KL-6 levels were 265 (1-409), 194 (47-352), 1149 (593-4407) and 3068 (726-9912) for the control, NEHI, SP-C and ABCA3 groups, respectively. When compared to the control and NEHI groups, median KL-6 levels were significantly higher in the SP-C (p<0.01; p=0.01, respectively) and ABCA3 groups (p<0.001; p=0.001, respectively); however, there was no difference between the control and NEHI groups (p=0.91). An inverse relationship was seen between KL-6 levels and age in the IESM group, but not in the NEHI or control groups. Children with NEHI had similar presenting clinical manifestations and were equally symptomatic at the time of KL-6 measurement as those with IESM.

Conclusions: Children with NEHI have normal KL-6 levels, in contrast to those with IESM, who have elevated serum KL-6 levels; serum KL-6 may be a useful biomarker in distinguishing between these entities when their clinical presentations overlap.