Background/Purpose:

The pathophysiology of joint disease in scleroderma, a heterogeneous multisystem disease mostly characterized by fibrosis, is unknown.  We performed proteomic analysis of serum in patients with scleroderma and joint tenderness.  Understanding systemic protein expression in scleroderma may help us understand joint disease in scleroderma.  Our goal was to characterize protein expression differences between scleroderma patients with joint tenderness and scleroderma patients without joint tenderness.

Methods:

Patients with scleroderma were recruited from the registry at Boston University Medical Center’s Scleroderma Center.  Serum (blood) samples were drawn and were analyzed with SOMAscan for 1129 protein biomarkers.  As part of the routine examination performed by a senior rheumatologist on all registry participants, tender joint count (0-18) was assessed on physical exam.  If a subject had a tender joint count of 2 or more, then that subject had joint disease.  If a subject had a tender joint count of 0, then that subject did not have joint disease.  For this study, 40 scleroderma subjects had both SOMAscan data and tender joint count assessment. One subject with only 1 tender joint count was excluded, so 39 subjects were analyzed.  For analysis, the biomarkers were log2 transformed, and differential expression analyses were performed using the “limma” package using the R statistical software. 

Results:

Among the 39 scleroderma subjects, 9 participants had joint pain (average tender joint count 4.9), and protein expression was compared between scleroderma participants with joint disease and scleroderma participants without joint disease.  The top 20 most significant biomarkers are shown in table 1.  In previous analyses (not shown), similar biomarkers (such as MMP (matrix metalloproteinase), fibrinogen, tumor necrosis factor), were seen elevated in all scleroderma participants (compared to normal subjects without scleroderma).   Notably, IL-6, cadherin-2 (involved in bone and cartilage formation), BRF1 (RNA Polymerase III transcription initiation factor subunit) were expressed higher in scleroderma subjects with joint disease compared to those without joint disease.  VEGF-121 (vascular endothelial growth factor) was expressed lower in scleroderma subjects with joint pain compared to those without joint disease. 

Conclusion:

Although scleroderma participants had many protein expression changes due to fibrosis, autoimmunity and vasculopathy, several biomarkers such as IL-6, cadherin-2, BRF1, VEGF-121 were differentially expressed in scleroderma participants with joint disease and could provide insight into the pathophysiology of joint disease in scleroderma.