Immunoglobulin‐degrading enzymes in localized juvenile periodontitis

Abstract

Previous reports have indicated the association of periodontal diseases with elevated levels of serum immunoglobulin G (IgG) antibodies to periodontally relevant bacteria. Recent results from this laboratory suggest that enzymes proteolytic for immunoglobulins are important virulence factors of several periodontal bacteria. Specifically, enzymes from Porphyromonas (Bacteroides) gingivalis culture supernatant fluid (SF) cleaved human IgG (4 subclasses), IgA1 and IgA2, IgM, IgD and IgE. Proteolytic enzymes from Actinobacillus actinomycetemcomitans culture SF cleaved IgG, IgA and IgM. An enriched Ig proteolytic preparation from Capnocytophaga ochracea culture SF was shown to extensively cleave all 4 subclasses of human IgG. Extensive degradation of IgG and IgA in crevicular fluid samples on SDS-PAGE from periodontal disease sites of localized juvenile periodontitis (LJP) patients in comparison to little degradation in healthy sites indicated the potential role the proteolytic enzymes from periodontopathogenic bacteria may play in situ. Treatment of IgG with P. gingivalis, A. actinomycetemcomitans and C. ochracea SF resulted in similar patterns of degradation. LJP patients had significantly higher levels of IgG and IgA proteolytic activity in whole saliva than age-, sex-, and race-matched periodontal disease-free controls. However, not all of the proteolytic activity could be ascribed to bacterial proteases since neutrophils are also present in large numbers at diseased sites. Using similar techniques, lysates of neutrophils from healthy controls cleaved IgG, IgA and IgM. The observation of enhanced Ig cleavage activity in crevicular fluid and saliva in LJP patients suggest a role for Ig proteolytic enzymes in LJP.

Characterization of a Novel Riboswitch-Regulated Lysine Transporter inAggregatibacter actinomycetemcomitans

“…Since all three of these ncRNAs are proposed to downregulate amino acid transport in the presence of high levels of intracellular amino acids, these data suggest that within the colony biofilm, A. actinomycetemcomitans possesses high intracellular amino acid concentrations. In the gingival crevice, A. actinomycetemcomitans and other bacteria are known to release proteases that could increase free amino acid pools in the surrounding environment (1,19). However, free amino acid levels have not been directly measured in gingival crevicular fluid.…”

The RgpA-Kgp Proteinase-Adhesin Complexes ofPorphyromonas gingivalisInactivate the Th2 Cytokines Interleukin-4 and Interleukin-5

“…Furthermore, the proteinases degrade C3b and C5b, thereby reducing the opsonization of the bacteria. In addition, the proteinases have been shown to degrade immunoglobulin G (IgG), IgA, IgM, IgD, and IgE and the T-cell surface markers CD4 and CD8, which decrease T-cell proliferation (5,6,8).…”

RgpA-Kgp Peptide-Based Immunogens Provide Protection againstPorphyromonas gingivalisChallenge in a Murine Lesion Model

“…Phagocytic and other functions of recruited neutrophils to the inflamed site may also be impaired, since the proteinases are capable of degrading cell surface receptors (20,22). The host immune response may be further dysregulated by the proteinases since they can degrade immunoglobulin G (IgG), IgA, IgM, IgD, and IgE antibodies (14,17).…”