Session Information
Date: Monday, November 9, 2015
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: In this study we aimed to both agonistically investigate alterations in the serum proteome of patients with diffuse cutaneous systemic sclerosis (dcSSc), as well as to identify differentially expressed proteins that correlate with disease severity cross-sectionally and longitudinally. Our goal was to identify a combination of serum proteins that would provide a biological measure of the extent of skin disease and thus have the potential to be used as a pharmacodynamic (PD) biomarker.
Methods: Sera from a cohort of dcSSc patients (n=12) were analyzed by SOMAscan aptamer technology (1129 proteins) for differences in protein levels compared to healthy control sera (n=4), and for correlation of protein levels with the modified Rodnan skin score (MRSS). In a separate cohort of patients, ELISAs were used to validate these proteins in cross-sectional samples (n=31) and in longitudinal samples (n=17). Mixed models were used to define a potential model for a PD biomarker composed of multiple proteins. This longitudinal model was then validated in an independent cohort (n=20). Baseline demographics for each of the four groups are included below.
Results: Forty-three analytes were identified as both differentially regulated in dcSSc patients compared to healthy controls, as well as correlated with MRSS (FDR<0.01). Ten proteins were tested for validation in a separate, larger cohort. Eight out of the ten proteins tested successfully validated as different from healthy controls and retained moderate cross-sectional correlations with the MRSS. These eight analytes were next examined for longitudinal change. The combination of two analytes (IL1R4 and Spondin-1) was used in a mixed model to best describe longitudinal change, and this model was successfully validated in an independent cohort.
Conclusion: In this study we have discovered that two novel proteins, not previously associated with SSc, are upregulated in patients and correlate with the extent of skin disease both cross-sectionally and longitudinally. Further, we have developed a PD biomarker based on levels of these proteins and show that this biomarker can be applied to assess changes in skin disease in dSSc patients over time, applicable to clinic or clinical trial settings.
|
Baseline Demographics |
Somalogic (n=12) |
Cross Sectional (n=31) |
Longitudinal 1 (n=17) |
Longitudinal 2 (n=20) |
|
Age (year) |
|
|
|
|
|
Mean (sd) |
50.9 (9.3) |
49.2 (12.5) |
48.7 (12.23) |
54.7 (9.4) |
|
Median (Range) |
50 (37-70) |
48 (21-71) |
48 (27-71) |
53 (34-71) |
|
Sex |
|
|
|
|
|
Percent Female (n) |
75% (9) |
70% (22) |
82% (14) |
55% (11) |
|
Percent Male (n) |
25% (3) |
29% (9) |
17% (3) |
45% (9) |
|
Modified Rodnan Skin Score |
|
|
|
|
|
Mean (sd) |
30.4 (6.8) |
20.4 (10.9) |
17.4 (11.5) |
22.5 (12.0) |
|
Median (Range) |
30 (21-42) |
19 (3-45) |
14 (2-45) |
22 (2-48) |
|
Disease duration (months) |
|
|
|
|
|
Mean (sd) |
12 (5.5) |
18.6 (17.9) |
24.8 (20.7) |
17.3 (12.7) |
|
Median (Range) |
12 (1-19) |
13 (2-82) |
16 (2-81) |
13 (2-57) |
To cite this abstract in AMA style:
Rice L, Mantero J, Stifano G, Ziemek J, Domsic RT, Lafyatis R. Developing and Validating a Serum Biomarker for the Extent of Skin Disease in Patients with Diffuse Cutaneous Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/developing-and-validating-a-serum-biomarker-for-the-extent-of-skin-disease-in-patients-with-diffuse-cutaneous-systemic-sclerosis/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/developing-and-validating-a-serum-biomarker-for-the-extent-of-skin-disease-in-patients-with-diffuse-cutaneous-systemic-sclerosis/