KL-6 as a Marker for Bronchiolitis Obliterans in Pediatric and Young Adult Bone Marrow Transplant Patients

Abstract

Bronchiolitis obliterans syndrome (BOS) is a serious complication of allogeneic bone marrow transplant (BMT). There is a need for a non-invasive diagnostic test in order to detect BOS in transplant recipients. KL-6 is a high molecular weight glycoprotein classified as MUC1 mucin that is expressed on the epithelial surface of type II alveolar cells in the lungs and is present on the surface of bronchiolar epithelial cells. KL-6 is an active chemotactic factor for fibroblasts which could play a role in the early pathogenesis of BOS. We hypothesize that serum KL-6 levels will be elevated in subjects with known BOS. This is a case control study that employs convenience sampling for KL-6 samples. It is a multi-center study. Serum samples were obtained from 15 subjects that underwent allogeneic BMT and 20 healthy controls between the ages of 6 months and 30 years. Of the 15 subjects that underwent BMT, 3 met the criteria for BOS. The definition of BOS was based upon pulmonary function tests (a sustained drop in FEV1 of 20% from pre-transplantation baseline) or biopsy. KL-6 levels were determined using a commercially available sandwich-type enzyme linked immunosorbent assay kit. Mean serum KL-6 levels +/− standard deviation for BMT subjects with BOS, BMT subjects without BOS and healthy controls were 571.6 +/−350.5, 302.3 +/−87.3 and 209.1 +/−77.6 U/ml, respectively. The difference between BMT subjects with BOS and those without BOS was statistically significant (p = 0.003) as well as those with BOS and healthy controls (p = 0.001). There was no statistical difference between BMT subjects without BOS and healthy controls (p = .956). KL-6 levels were significantly elevated in BMT subjects with BOS as compared those without BOS and healthy controls. KL-6 could serve as a diagnostic tool in detecting BOS in BMT recipients.