Author(s)
Matthew L. Rohlfing, MD1
Alexander T. Hillel, MD2
Elizabeth Wohler, MS3
Nara Sobreira, MD, PhD2
Elizabeth J. Phillips, MD4
Simon A. Mallal, MBBS4
Evan Clark, BS5
Alexander Gelbard, MD5
Affiliation(s)
1 . Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO
2 . Department Otolaryngology – Head and Neck Surgery, Johns Hopkins University; Baltimore, MD
3 . McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University; Baltimore, MD
4 . Department of Medicine, Vanderbilt University Medical Center; Nashville, TN
5 . Department of Otolaryngology, Vanderbilt University Medical Center; Nashville, TN
Abstract:
Objective: Despite much recent progress, idiopathic subglottic stenosis (iSGS) remains incompletely understood. Demographic homogeneity of affected patients has raised interest in possible genetic predisposition. In other inflammatory disorders, variations in killer cell immunoglobulin-like receptor (KIR) allele expression are involved via activating and inhibiting effects on NK cells. Dysregulated immune activation including NK cell predominance has been identified in iSGS subglottic scar specimens. This study interrogates iSGS disease association with KIR genetic polymorphisms.
Methods: High resolution KIR typing of 21 iSGS patients was compared with 2,130 unaffected healthy Northern American Caucasians.
Results: KIR genotyping demonstrated significant differences between the iSGS and control populations. This included over-expression of 10 inhibitory KIR alleles and 5 activating alleles.
Conclusions: The over-representation of specific KIR alleles suggests a novel genetic basis for iSGS expression and predisposition. Other studies of iSGS have shown that abnormal adaptive immune activation contributes to fibrosis and airway obstruction in the subglottis. This is in parallel with epithelial barrier dysfunction and disruption of the proximal airway microbiome. Unique KIR expression may be linked to the pathologic adaptive immune response and over-representation of CD8+ T cells, CD4+ Treg cells, and NK cells in the subglottis of patients with iSGS.