Leukocyte Adhesion Deficiency Type 1 (LAD-1) is a rare autosomal recessive condition caused by a mutation in the beta-2 integrin chain (ITGβ2-CD18), a cell membrane glycoprotein. Neutrophils of LAD-1 patients present with heterogeneous molecular defects in the CD18 subunit and functional defects in adhesion. Clinically, the hallmark of LAD-1 is recurrence of bacterial infections, including severe periodontitis.
In this pilot study, we characterized the microbial diversity in subgingival biofilms of patients with LAD-1 periodontitis and compared them to that of health and chronic periodontitis.
Patients diagnosed with LAD-1 were clinically evaluated and subgingival biofilm samples were collected from three patients. 16S rRNA genes were amplified by PCR from DNA extracted from biofilms. DNA-DNA hybridization was performed using the Human Oral Microbe Identification Microarray (HOMIM) for over 300 bacterial species or groups. Microbial profiles with relative abundance levels were analyzed with principal component analysis, partial least squares regression analysis and multidimensional scaling.
All LAD-1 patients evaluated were diagnosed with periodontal disease (AAP criteria) and severity of periodontal disease correlated with severity of systemic clinical findings and residual expression of CD18 on neutrophils.
Several bacterial species were associated with biofilms from LAD-1 patients. These included: Leptotrichia buccalis, Leptotrichia goodfellowii, Sneathia sanguinegens, Fusobacterium nucleatum, Selenomonas noxia, Campylobacter gracilis, Capnocytophaga granulosa, Campylobacter concisus, Campylobacter rectus, Campylobacter gracilis, Parvimonas micra, Eubacterium saburreum, Eubacterium brachy, Parvimonas micra, and Campylobacter showae.
Microbial profiles of LAD-1 periodontal biofilms showed some variations between individuals but were significantly different from chronic periodontitis and health. Most species found associated with biofilms of LAD-1 patients are not typically associated with periodontal disease in patients without LAD-1. Identification of specific species involved in this severe form of periodontitis in LAD-1 will aid in the understanding of the role of neutrophil mediated responses in the maintenance of periodontal health.
Keywords: Immunology, Inflammation, Microbiology and Periodontal disease