Systemic sclerosis (SSc), most commonly known as scleroderma, is an autoimmune disease characterized by fibrotic scarring of the skin and, in the most severe cases, organs. This disease is divided into two subtypes known as limited cutaneous systemic sclerosis (lcSSc) and diffuse cutaneous systemic sclerosis (dcSSc) with the latter carrying the worst prognosis. This disease is driven by the excessive production of collagen. In systemic sclerosis, this excess collagen can form fibrotic tissue on the affected organs, which most commonly are: the skin, GI tract, heart and lungs. The complications of this disease are primarily due to lung involvement where the fibrotic tissue can cause Interstitial Lung Disease (ILD) and Pulmonary Arterial Hypertension and both of them carry a poor prognosis. My desire is to elucidate the underlying pathology of this disease and how it carries on to lung involvement in order to develop the adequeate treatments for these complications.
I believe this is one the main paper on systemic sclerosis:
Baroni SS, Santillo M, Bevilacqua F, et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med. 2006;354(25):2667‐2676. doi:10.1056/NEJMoa052955
And from the same group:
Luchetti MM, Moroncini G, Jose Escamez M, et al. Induction of Scleroderma Fibrosis in Skin-Humanized Mice by Administration of Anti-Platelet-Derived Growth Factor Receptor Agonistic Autoantibodies. Arthritis Rheumatol. 2016;68(9):2263‐2273. doi:10.1002/art.39728
I would recommend you this review from my lab and collaborators.
Article The Primary Cilium: Emerging Role as a Key Player in Fibrosis
The primary cilium and the anti-PDGF stimulatory auto-antibodies are both fascinating proposals. The latter was in a 2006 NEJM paper. Have there been F-Up and confirmatory papers ?
It is important to look at systemic sclerosis as a vascular disease and not focus entirely on later stage fibrosis. Research suggests that endothelial damage is an early stage of the disease process that leads to downstream fibrosis and organ damage through mechanisms that increasingly well understood. While these provide nature targets for pharmacological interventions, it probably makes more sense to focus on what is leading to the early endothelial damage. This might lead to interventions that can interrupt the disease process at an early stage, preventing fibrosis and organ damage. It is worth noting that blood rheology in SSc is highly abnormal, with overall elevated whole blood viscosity and abnormal clumping of red blood cells (not just Rouleaux formations). Whether or not the abnormal blood rheology is etiopathogenic is not currently known, but may be a fruitful area for further research.