A CRITICAL EXAMINATION OF AUTOIMMUNITY AND INFLAMMATION

ABSTRACT

Autoinflammatory and autoimmune disorders are characterized by aberrant changes in innate and adaptive immunity that may lead from an initial inflammatory state to an organ specific damage. These disorders possess heterogeneity in terms of affected organs and clinical phenotypes. However, despite the differences in etiology and phenotypic variations, they share genetic associations, treatment responses and clinical manifestations. The mechanisms involved in their initiation and development remain poorly understood, however the existence of some clear similarities between autoimmune and autoinflammatory disorders indicates variable degrees of interaction between immune-related mechanisms. This study sought to critically examine autoimmunity and inflammation. The study evaluated similarities and specificities of pathway activity changes in twelve autoimmune and autoinflammatory disorders by performing meta-analysis of publicly available gene expression datasets generated from peripheral blood mononuclear cells, using a bioinformatics pipeline that inte- grates Self Organizing Maps and Pathway Signal Flow algorithms along with KEGG pathway topologies. The results reveal that clinically divergent disease groups share common pathway perturbation profiles. Thus, the data suggest that while all of the studied diseases are affected by activation of common inflammatory processes, disease-specific variations in their relative balance are also identified.

TABLE OF CONTENTS

ABSTRACT

CHAPTER ONE

1.0  INTRODUCTION

1.1  BACKGROUND TO THE STDUY

1.2  STATEMENT OF PROBLEM

1.3  PURPOSE OF THE STUDY

CHAPTER TWO

2.0  LITERATURE REVIEW

2.1  CONCEPTUAL REVIEW

2.2  THE INITIATION OF AUTOIMMUNITY

2.3  THE PROPAGATION OF AUTOIMMUNE REACTIONS

2.4  THE RESOLUTION OF AUTOIMMUNITY

2.5  FUTURE PROSPECTS

CHAPTER THREE

3.0  MATERIAL AND METHODS

3.1  DATA SOURCES

3.2  DATASET PREPROCESSING

3.3  PATHWAY SIGNAL FLOW CALCULATION

3.4  SPOT BASED DISEASE SIMILARITY ASSESSMENT

CHAPTER FOUR

4.0  RESULTS AND DISCUSSION

4.1  RESULTS

CHAPTER FIVE

5.0  SUMMARY AND CONCLUSIONS

5.1  SUMMARY

5.2  CONCLUSION

REFERENCES