Link Found Between Angiogenesis, Vessel Destruction, and Fibrosis in SSc

Last week's articles on rheumatology topics in the major non-rheumatology journals.

Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic SclerosisNew England Journal of Medicine, December 18, 2013

New research suggests that the platelet-derived chemokine CXCL4 has a significant role in the vascular destruction and in fibrosis of systemic sclerosis (SSc). Plasmacytoid dendritic cells secrete type I interferon and CXCL4, and the upregulation of those two cytokines is associated with many autoimmune diseases.

This study compared levels of CXCL4 in 20 healthy controls to those in 54 patients with SSc, and confirmed the results in larger replication cohorts.

Levels of CXCL4 secreted by the plasmacytoid dendritic cells were significantly higher in SSc than in controls or in other autoimmune diseases.

CXCL4 was much higher in early diffuse SSc, lower in late diffuse SSc, still lower in limited SSc, and lowest in controls. CXCL4 also predicted progression of SSc phenotypes.

CXCL4 is one of the most potent antiangiogenic chemokines. (Plasma from SSc patients is also antiangiogenic.) CXCL4 inhibits vascular endothelial growth factor (VEGF).

SSc is characterized by the rarefaction of vessels, and the absence of neovascularization despite the presence of multiple proangiogenic factors including VEGF.

CXCL4 also stimulates fibrosis by inhibiting interferon-γ, which is antifibrotic.

CXCL4 is necessary but not sufficient for sclerosis. High levels of CXCL4 are found in Raynaud’s phenomenon, which does not often progress to SSc.

Also new last week:

Case 39-2013 - A 57-Year-Old Woman with Painful Bullous Skin LesionsNew England Journal of Medicine, December 19, 2013

Painful Bullous Skin LesionsNow@NEJM, December 20, 2013

Over 19 months, a 57-year-old woman had recurring hospitalizations for painful erosions and flaccid blisters, with mucosal involvement during one episode, multiple markers of rheumatic diseases, and three skin biopsies. Each biopsy suggested a different diagosis: erythema multiforme, bullous lupus erythematosus (a subtype of systemic lupus erythematosus [SLE]), and pemphigus foliaceus.

She was finally diagnosed with pemphigus erythematosus, an overlap disorder of pemphigus foliaceus and SLE.

The lesions were responsive to prednisone, but for religious reasons, she was reluctant to take medications, often refused them, and was distrustful of the medical system. She refuses to believe that she has SLE, and so her doctors agreed to focus on her skin disease.

In the most recent admission, she presented with multiple flaccid bullous lesions and superficial erosions, with crusting and mild oozing on the chest, back, abdomen, and both arms and shoulders. She described her pain as 8 on a scale of 10 (with 10 the most severe).

Allelic-Dependent Expression of an Activating Fc Receptor on B Cells Enhances Humoral Immune Responses.
Science Translational Medicine, December 18, 2013

In a feedback loop, B cells have receptors, called FcγRIIb, that downregulate their IgG production.

Now, in about 15% of the population, researchers have found another receptor on B cells that upregulates IgG production, which they named FcγRIIc. It increases their response to anthrax vaccine, and is a risk factor in lupus and multiple sclerosis.