Pep19 drives epitope spreading in periodontitis and periodontitis‐associated autoimmune diseases

Ey, Kwon; G.S.Cha,; Jeong, Eun-Seon; Lee, Jun-Yeop; Kim, S.-J.; Surh, Charles D.; Choi, Jaeho

doi:10.1111/jre.12318

Cited by 14 publications

(21 citation statements)

References 45 publications

(89 reference statements)

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“…Pep19 reacted more strongly in the type 1 DM group than in the healthy groups, and showed a strong reaction in the autoimmune disease group. This corresponds to the results of our previous study, in which robust reactivity to anti-Pep19 monoclonal antibody was detected at the inflammation site (i.e., in gingival connective tissue lesions and atheromatous plaques) in contrast to normal healthy sites [13]. Based on these results, Pep19 is a key factor for HSP epitope-specific therapy for autoimmune disease control [161718].…”

Section: Discussionsupporting

confidence: 88%

“…Serum reactivity to human autoantigen Hu9 is not observed in any healthy subjects but in type 1 DM. Figure 2 was reproduced and modified from Kwon et al [13] with permission of the Journal of Periodontal Research. …”

Section: Resultsmentioning

confidence: 99%

“…In our previous study, we established intramolecular epitope spreading into Hu9 in the sera of periodontitis and infection-induced autoimmune disease patients. As support for the cellular mechanisms responsible for this phenomenon, a T-cell proliferative response to Hu9 was observed [13]. Therefore, the Hu9 autoantigen is an important epitope in individuals with autoimmune disease, and Pep19 initiated the dot immunoblot reaction in both the healthy and autoimmune disease groups.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous research [111213], PgHSP60 and Pep19 were found to be the dominant epitopes in individuals with periodontitis and autoimmune disease. The present study showed the same results, in that the highest serum immunoblot intensity was observed with Pep19 or whole PgHSP60 in all subjects.…”

Section: Discussionmentioning

confidence: 99%

“…HSP60 from P. gingivalis (PgHSP60) and peptide 19 (TLVVNRLRGSLKICAVKAPG) from PgHSP60 (Pep19) are immunodominant epitopes in autoimmune disease patients [11], including those with periodontitis [12]. In addition, Pep19 has been shown to drive epitope spreading in periodontitis and periodontitis-associated autoimmune disease [13]. However, it remains unclear whether Pep19 is a dominant epitope in subjects without periodontitis or autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Robust immunoreactivity of teenager sera against peptide 19 from Porphyromonas gingivalis HSP60

Kwon

Sun

Joo

et al. 2017

J Periodontal Implant Sci

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PurposeEpitope spreading is a phenomenon in which distinct subdominant epitopes become major targets of the immune response. Heat shock protein (HSP) 60 from Porphyromonas gingivalis (PgHSP60) and peptide 19 from PgHSP60 (Pep19) are immunodominant epitopes in autoimmune disease patients, including those with periodontitis. It remains unclear whether Pep19 is a dominant epitope in subjects without periodontitis or autoimmune disease. The purpose of this study was to determine the epitope spreading pattern and verify Pep19 as an immunodominant epitope in healthy teenagers using dot immunoblot analysis. The patterns of epitope spreading in age-matched patients with type 1 diabetes mellitus (type 1 DM) and healthy 20- to 29-year old subjects were compared with those of healthy teenagers.MethodsPeptide from PgHSP60, Mycobacterium tuberculosis HSP60 (MtHSP60), and Chlamydia pneumoniae HSP60 (CpHSP60) was synthesized for comparative recognition by sera from healthy subjects and patients with autoimmune disease (type 1 DM). Dot immunoblot analysis against a panel of peptides of PgHSP60 and human HSP60 (HuHSP60) was performed to identify epitope spreading, and a densitometric image analysis was conducted.ResultsOf the peptide from PgHSP60, MtHSP60, and CpHSP60, PgHSP60 was the predominant epitope and was most consistently recognized by the serum samples of healthy teenagers. Most sera from healthy subjects and patients with type 1 DM reacted more strongly with PgHSP60 and Pep19 than the other peptides. The relative intensity of antibody reactivity to Pep19 was higher in the type 1 DM group than in the healthy groups.ConclusionsPep19 is an immunodominant epitope, not only in autoimmune disease patients, but also in healthy young subjects, as evidenced by their robust immunoreactivity. This result suggests that the Pep19-specific immune response may be an initiator that triggers autoimmune diseases.

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