Introduction

Rheumatoid arthritis (RA) is a disease affecting around 1% of the population in the United Kingdom. Typically, RA onset is in the fifth decade of life, but disease onset at an earlier age is frequent. RA affects mainly the small joints of hands and feet, causing pain, disability and, if not treated, joint destruction. The exact cause of the disease is not known, but it is established that the immune system of the patient is attacking  his own joints - therefore, RA is classified as an autoimmune disease.

Based on the presence or absence of antibodies called anti-citrullinated peptide antibodies (ACPA), RA can be classified as ACPA+ or ACPA- disease. ACPA+ RA is usually more severe than ACPA- RA, though several patients with ACPA+ RA have a milder disease course, while  several patients with ACPA- RA have a more severe disease course. Therefore, ACPA cannot be used predict for sure which patients will develop a disabling disease and should be treated more aggressively at disease onset.

Identifying genetic markers of rheumatoid arthritis severity:

One of my research focus consists of identifying genetic polymorphisms (=small differences in genes between patients) which would allow rheumatologists to predict which patients will go on and develop a severe disease course in the future. Several genetic markers predisposing healthy individuals to develop RA have been identified so far, but it is not clear if and how those susceptibility polymorphisms affect disease course. I am therefore testing RA susceptibility polymorphisms for their association with disease severity and I am trying to identify new markers of disease severity, which would be different to the markers of RA susceptibility.

Studying the genetic differences between two different types of rheumatoid arthritis:

Most genetic studies which identified susceptibility markers for RA have been performed in patients' groups comprising a vast majority of ACPA+ patients. Therefore, little is known on the genetics of ACPA- RA. Another focus of interest consists of comparing the genetic markers of ACPA+ RA with those of ACPA- RA and of identifying new genetic markers of ACPA- RA.