26th January 2024

Background

Epidemiology

Mixed Connective Tissue Disease is an autoimmune overlap syndrome that presents with clinical features of SLE, systemic sclerosis and polymyositis. It is characterised by presence of high titers of a distinctive autoantibody, now called anti-U1 ribonucleoprotein (RNP) (previously termed antibody to extractable nuclear antigens, anti-ENA).

Worldwide, the prevalence is estimated to be between 2-3.8 cases per 100,000 population. It is much more common in females than males, with an estimated ratio of 3:1 and the typical age of onset is between 15-25 years; however, it can occur at any age. MCTD occurs in patients of all ethnicities, but the clinical manifestations, particularly the frequency of end-organ involvement can vary.

Pathophysiology

Whilst the exact genetic cause is unknown, DNA methylation levels may be relevant as patients with MCTD have been found to have decreased levels of DNA methylation. There has also been a genetic association with major histocompatibility genes such as HLA-B*08 and HLA-B1*04. 

These genetic abnormalities lead to B-lymphocyte hyperactivity, resulting in high levels of auto-antibodies (namely anti–U1-RNP and anti–U1-70 kd autoantibodies). These auto-antibodies then cause T-lymphocyte activation, which leads to lymphocytic and plasmacytic infiltration of tissues, causing increased vascular endothelial apoptosis.