Oral mucositis and periodontal disease in patients with primary or acquired immunodeficiencies
Author: Ye, Ying
Date: 2013-10-04
Location: Karolinska Institutet, sal 4V, plan 4, Alfred Nobels allé 8, Huddinge.
Time: 09:00
Department: Inst för odontologi / Dept of Dental Medicine
Abstract
The infection and inflammation in the oral cavity are commonly related to the skewed interaction between host immunity and inhabiting microorganisms. Both primary and acquired immunodeficiency conditions are frequently associated with oral symptoms. In this thesis two oral manifestations, chronic periodontitis and oral mucositis, were investigated in patients with severe congenital neutropenia and in patients with malignant diseases respectively.
In Paper I, a genotype-phenotype correlation between ELANE mutations and chronic periodontal disease was described in a group of patients with severe congenital neutropenia. Patients that harbor mutations in the gene ELANE, encoding neutrophil elastase, presented with poorer periodontal health as compared to those with HAX1 mutations or unknown mutations. The periodontal pockets of the patients with ELANE mutations displayed a skewed microflora and elevated levels of proinflammatory cytokine IL-1β.
In Paper II and III we studied the oral mucositis, an acute side effect frequently encountered during cytostatic chemotherapy, in a group of pediatric patients diagnosed with various types of malignancies. In Paper II, we showed that at the time of malignancy diagnosis, patients with acute leukemia had highest risk of oral mucositis, presenting with high concentrations of inflammatory cytokines IL-6, IL- 8, IL-10, and TNF-α and low levels of pro-LL-37 (hCAP-18) in the blood plasma.
In Paper III we conducted high-throughput sequencing of the oral mucosal bacterial community in an attempt to investigate the role of bacteria in the pathogenesis of oral mucositis development. At the time of malignancy diagnosis, patients who later developed oral mucositis were found to have higher oral mucosal microbial diversity and were more heterogeneous among one another compared to those that did not develop mucositis. A more pronounced modification of the bacterial community by chemotherapy was detected in patients that later developed oral mucositis, indicating a beneficial role of stable oral microbiota.
In the last paper of this thesis, we investigated the variation of blood pro-LL-37 levels in a cohort of patients presenting with chronic neutropenia. The lower values of pro-LL-37 were found in cases with severe congenital neutropenia, as compared to autoimmune, idiopathic, and ethnic neutropenia. The findings support the view that benign forms of neutropenia could be distinguished from the severe forms at an early stage. Plasma pro-LL-37 levels may potentially work as a diagnostic parameter and this analysis could be developed for clinical use.
Providing adequate and personalized oral care to the patients with immunodeficiencies has necessitated more knowledge regarding the predisposition and pathobiology of their oral manifestations. The findings in this thesis may benefit the clinical management and subsequently improves the patient’s quality of life.
In Paper I, a genotype-phenotype correlation between ELANE mutations and chronic periodontal disease was described in a group of patients with severe congenital neutropenia. Patients that harbor mutations in the gene ELANE, encoding neutrophil elastase, presented with poorer periodontal health as compared to those with HAX1 mutations or unknown mutations. The periodontal pockets of the patients with ELANE mutations displayed a skewed microflora and elevated levels of proinflammatory cytokine IL-1β.
In Paper II and III we studied the oral mucositis, an acute side effect frequently encountered during cytostatic chemotherapy, in a group of pediatric patients diagnosed with various types of malignancies. In Paper II, we showed that at the time of malignancy diagnosis, patients with acute leukemia had highest risk of oral mucositis, presenting with high concentrations of inflammatory cytokines IL-6, IL- 8, IL-10, and TNF-α and low levels of pro-LL-37 (hCAP-18) in the blood plasma.
In Paper III we conducted high-throughput sequencing of the oral mucosal bacterial community in an attempt to investigate the role of bacteria in the pathogenesis of oral mucositis development. At the time of malignancy diagnosis, patients who later developed oral mucositis were found to have higher oral mucosal microbial diversity and were more heterogeneous among one another compared to those that did not develop mucositis. A more pronounced modification of the bacterial community by chemotherapy was detected in patients that later developed oral mucositis, indicating a beneficial role of stable oral microbiota.
In the last paper of this thesis, we investigated the variation of blood pro-LL-37 levels in a cohort of patients presenting with chronic neutropenia. The lower values of pro-LL-37 were found in cases with severe congenital neutropenia, as compared to autoimmune, idiopathic, and ethnic neutropenia. The findings support the view that benign forms of neutropenia could be distinguished from the severe forms at an early stage. Plasma pro-LL-37 levels may potentially work as a diagnostic parameter and this analysis could be developed for clinical use.
Providing adequate and personalized oral care to the patients with immunodeficiencies has necessitated more knowledge regarding the predisposition and pathobiology of their oral manifestations. The findings in this thesis may benefit the clinical management and subsequently improves the patient’s quality of life.
List of papers:
I. YING YE, Göran Carlsson, Biniyam Wondimu, Annika Fahlén, Jenny Karlsson-Sjöberg, Mats Andersson, Lars Engstrand, Tülay Yucel-Lindberg, Thomas Modéer, Katrin Pütsep. Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia. Journal of Clinical Immunology. 2011; 31(6): 936-45.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. YING YE, Göran Carlsson, Monica Barr Agholme, Jenny Karlsson-Sjöberg, Tülay Yucel-Lindberg, Katrin Pütsep, Thomas Modéer. Pretherapeutic plasma pro- and anti- inflammatory mediators are related to high risk of oral mucositis in pediatric patients with acute leukemia: a prospective cohort study. PLoS ONE. 2013; 8(5): e64918.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. YING YE, Göran Carlsson, Monica Barr Agholme, John A.L. Wilson, Annika Roos, Birgitta Henriques-Normark, Lars Engstrand, Thomas Modéer, Katrin Pütsep. Oral bacterial community dynamics in paediatric patients with malignancies in relation to chemotherapy-related oral mucositis: a prospective study. Clinical Microbiology and Infection. 2013
Fulltext (DOI)
Pubmed
IV. YING YE, Göran Carlsson, Jenny Karlsson-Sjöberg, Niels Borregaard, Thomas Modéer, Mats Andersson, Katrin Pütsep. Plasma pro-LL-37 level as a diagnostic tool in the evaluation of chronic neutropenia: a prospective study. [Manuscript]
I. YING YE, Göran Carlsson, Biniyam Wondimu, Annika Fahlén, Jenny Karlsson-Sjöberg, Mats Andersson, Lars Engstrand, Tülay Yucel-Lindberg, Thomas Modéer, Katrin Pütsep. Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia. Journal of Clinical Immunology. 2011; 31(6): 936-45.
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. YING YE, Göran Carlsson, Monica Barr Agholme, Jenny Karlsson-Sjöberg, Tülay Yucel-Lindberg, Katrin Pütsep, Thomas Modéer. Pretherapeutic plasma pro- and anti- inflammatory mediators are related to high risk of oral mucositis in pediatric patients with acute leukemia: a prospective cohort study. PLoS ONE. 2013; 8(5): e64918.
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. YING YE, Göran Carlsson, Monica Barr Agholme, John A.L. Wilson, Annika Roos, Birgitta Henriques-Normark, Lars Engstrand, Thomas Modéer, Katrin Pütsep. Oral bacterial community dynamics in paediatric patients with malignancies in relation to chemotherapy-related oral mucositis: a prospective study. Clinical Microbiology and Infection. 2013
Fulltext (DOI)
Pubmed
IV. YING YE, Göran Carlsson, Jenny Karlsson-Sjöberg, Niels Borregaard, Thomas Modéer, Mats Andersson, Katrin Pütsep. Plasma pro-LL-37 level as a diagnostic tool in the evaluation of chronic neutropenia: a prospective study. [Manuscript]
Institution: Karolinska Institutet
Supervisor: Modéer, Thomas
Issue date: 2013-09-11
Rights:
Publication year: 2013
ISBN: 978-91-7549-233-9
Statistics
Total Visits
Views | |
---|---|
Oral ...(legacy) | 1521 |
Oral ... | 290 |
Total Visits Per Month
October 2023 | November 2023 | December 2023 | January 2024 | February 2024 | March 2024 | April 2024 | |
---|---|---|---|---|---|---|---|
Oral ... | 2 | 1 | 0 | 4 | 0 | 2 | 1 |
File Visits
Views | |
---|---|
Thesis_Ying_Ye.pdf(legacy) | 866 |
Spikblad_Ying_Ye.pdf(legacy) | 279 |
Thesis_Ying_Ye.pdf | 219 |
Spikblad_Ying_Ye.pdf | 37 |
YE_Thesis.pdf(legacy) | 3 |
YE_Spikblad.pdf(legacy) | 2 |
Top country views
Views | |
---|---|
United States | 657 |
Germany | 307 |
China | 127 |
Sweden | 119 |
Russia | 26 |
India | 22 |
South Korea | 21 |
United Kingdom | 17 |
Denmark | 14 |
Finland | 12 |
Top cities views
Views | |
---|---|
Kiez | 114 |
Ashburn | 59 |
Sunnyvale | 58 |
Stockholm | 49 |
Beijing | 24 |
Romeo | 15 |
Seoul | 15 |
Shenzhen | 13 |
Ballerup | 11 |
Düsseldorf | 11 |