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Recurrent Respiratory Papillomatosis: Studies of Immune Dysregulation Differential expression of genes in patients with Recurrent Respiratory Papillomatosis

Nilsson, Maile (2018) MOBM01 20181
Degree Projects in Molecular Biology
Popular Abstract
Recurrent Respiratory Papillomatosis: Studies of Immune Dysregulation

Recurrent respiratory papillomatosis (RRP) is a disease caused by two specific low-risk types of human papillomavirus (HPV), HPV 6 and HPV 11. Benign tumors known as papillomas can grow in the respiratory tracts of patients afflicted with the disease. The papillomas growing in the respiratory tract can disrupt the vocal folds of the patient and cause hoarseness, breathing problems, chronic coughing, and difficulty swallowing. There is no cure for RRP. Standard treatment is surgical removal of the papillomas. Even after successful surgical removal of the papillomas, patients are subject to recurrence and must have multiple surgeries throughout their lifetime.... (More)
Recurrent Respiratory Papillomatosis: Studies of Immune Dysregulation

Recurrent respiratory papillomatosis (RRP) is a disease caused by two specific low-risk types of human papillomavirus (HPV), HPV 6 and HPV 11. Benign tumors known as papillomas can grow in the respiratory tracts of patients afflicted with the disease. The papillomas growing in the respiratory tract can disrupt the vocal folds of the patient and cause hoarseness, breathing problems, chronic coughing, and difficulty swallowing. There is no cure for RRP. Standard treatment is surgical removal of the papillomas. Even after successful surgical removal of the papillomas, patients are subject to recurrence and must have multiple surgeries throughout their lifetime. Childhood onset, known as juvenile RRP, is typically more aggressive and recurrent than adult RRP. A mother can transmit HPV to her child in utero or during childbirth. The prevalence of RRP is between 1 and 4 per 100,000.

HPV is able to modify the immune response of RRP patients. The immune system recognizes exposure and produces specific antibodies directed at the viruses. But patients develop a tolerance to the virus instead of an anti-HPV response that would normally clear or contain the infection. It is unknown how these viruses elude the immune system and why cells infected with the virus grow into papillomas. Understanding the transcriptional profile of RRP papillomas and how it differs from normal adjacent tissue can help identify the genes responsible for RRP pathogenesis.

The purpose of this project is to investigate differential gene expression between diseased papilloma tissue, and adjacent healthy tissue of RRP patients. Paired tissue samples from clinical patients were used to compare how specific immune system and tumor development genes are expressed. NanoString Technologies nCounter PanCancer Pathways Panel data of 11 patient samples (paired sets of papilloma and healthy adjacent tissue) was compared to identify differentially expressed genes with a log2 fold change of 1.5 or higher. qRT-PCR was then used to confirm the NanoString results. Fifteen genes of interest were studied, with transcripts of these genes cloned and used as positive controls in qRT-PCR. Of the 15 genes identified, the differential expression levels of 11 have been confirmed. Adaptive immune response and chemokine/receptor genes CCL14, CCL18, CCL21, CXCL12, CD79A, F13A1, and IFNG were found to be downregulated in the papillomas. Innate immune response genes CDKN1A, S100A12, S100A7, and IL8 were found to be upregulated in the papillomas.

Identifying specific immunogenic and tumor related genes responsible for immune dysregulation and papilloma growth is important because these genes have the potential to be potential targets for further studies, and could lead to the development of future treatments and cures. This thesis work contributes to the understanding of the transcriptional profile of RRP papillomas.

Master’s Degree Project in Molecular Biology, 30 credits 2018
Advisors: Dr. Ola Forslund and Dr. Stefan Schwartz
Department: Medical Microbiology and Laboratory Medicine, BMC, Lund University
Location: Region Skåne Clinical Microbiology Laboratory (Less)
Please use this url to cite or link to this publication:
author
Nilsson, Maile
supervisor
organization
course
MOBM01 20181
year
type
H1 - Master's Degree (One Year)
subject
language
English
id
8960383
date added to LUP
2018-10-17 13:45:52
date last changed
2018-10-17 13:45:52
@misc{8960383,
  author       = {{Nilsson, Maile}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Recurrent Respiratory Papillomatosis: Studies of Immune Dysregulation Differential expression of genes in patients with Recurrent Respiratory Papillomatosis}},
  year         = {{2018}},
}