Session Information
Date: Sunday, November 13, 2016
Title: Vasculitis - Poster I: Large Vessel Vasculitis and Polymyalgia Rheumatica
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Giant Cell Arteritis (GCA) is considered an urgent condition in Rheumatology, due to high risk of permanent vision loss and cerebro-vascular insults. No diagnostic or prognostic markers are yet known for GCA. While erythrocyte sedimentation rate (ESR) is part of the ACR 1990 GCA classification criteria, other acute phase proteins could represent an added value for distinguishing between GCA/non-GCA and GCA remission/recurrence. The aimsof our cross-sectional study were to a) measure serum levels of 40 selected biomarkers in 95 patients with GCA and 42 nonGCA patients, b) determine the associations of the biomarkers with GCA diagnosis, clinical complications and disease relaps.
Methods: Sera were collected from newly diagnosed (still steroid naive) GCA patients and nonGCA controls at time of first visit. GCA patients were followed carefully for the first year looking at signs and symptoms of relapsing disease. Sera proteins (Chitinase-3 Like-1, ICAM-1, VCAM-1, IL-1α, IL-1β, IL-1RI, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-22, IL-23, IL-33, MMP-1,-2, -3, -9, -12, TNFα, Leptin, Resistin, IFN-γ, CD62L, TNFRI,IP-10, LIF, MIG, α-Fetoprotein, MCP-1) were measured by Luminex platform. SAA, CRP, haptoglobin, fibrinogen, ferritin, hemopexin, orosomucoid, albumin were measured by nephelometry.
Results: Acute phase proteins SAA, CRP, haptoglobin, ferritin, hemopexin, orosomucoid and albumin all showed significant association with GCA diagnosis, in addition to elevated ESR, leukocyte and thrombocyte counts (Table). The highest diagnostic value was observed for SAA and CRP (n=92/93 and n=94/95, both 98.9%), followed by ESR (n=93/95, 97.9%). Patients with afterward visual disturbances had significantly lower levels of acute phase proteins: SAA (median (IQR):143 (51-290) vs. 270 (95-680) g/l), CRP (51 (28-86) vs. 73 (41-139) g/l), haptoglobin (3.7 (3-5.8) vs. 5.1 (3.6-6.5) g/l), and ESR (70 (52-88) vs. 89 (61-111) mm/h), while showing significantly elevated levels of VCAM-1 (824 (629-965) vs 502 (326-677) ng/ml) as compared to patients without visual disturbances. Among all the markers tested VCAM-1 had the highest area under ROC curve (AUC) (0.818) for visual disturbances. VCAM-1 was also significantly associated with extracranial artery disease. GCA patients who relapsed during follow-up, had significantly higher levels of SAA (311 (177-765) vs. 154 (41-418) g/l), CRP (86 (48-141) vs. 55 (32-120) g/l), ESR (94 (70-108) vs. 70 (52-90) mm/h), leukocyte counts (10.3 (8.7-12.3) vs. 9.1 (7-10.4)*109/l) at the disease onset.
Conclusion: Testing multiple acute phase proteins with additional blood parameters and biomarkers can represent an added value to earlier diagnosis, as well as optimize prediction of relapses and complications, such as visual disturbances and extracranial artery involvement. Table: Association of biomarkers with diagnosis GCA
| Name of biomarker Cut off | Median (IQR) GCA | Median (IQR) non GCA |
p |
Diagnostic sensitivity (% positives in patients) |
OR (95% CI) |
AUC under ROC for diagnosis |
| SAA 6.4 g/l | 205.3 (26-474) N=93 | 23 (2.0-220.5) N=30 |
<0.001 |
98.9 |
33.5 (4.0-281.6) |
0.281 |
| CRP 5 g/l | 66 (35-124) N=95 | 14.5 (5-56) N=42 |
<0.001 |
98.9 |
37.6 (4.6-301.3) |
0.320 |
| Haptoglobin 2 g/l | 4.9 (3.4-6.2) N=82 | 3.0 (1.45-4.25) N=17 |
<0.001 |
96.3 |
18.4 (4.09-82.9) |
0.195 |
| Fibrinogen 3.5 g/l | 7.6 (6.3-8.5) N=56 | 6.9 (5.1-8.2) N=15 |
0.155 |
98.3 |
/ |
/ |
| Ferritin F 120; M 300 µg/l | 331 (158-482) N=86 | 271 (131-637) N=39 |
0.874 |
69.3 |
/ |
/ |
| Hemopexin 1.15 g/l | 1.4 (1.2-1.5) N=43 | 1.2 (1.1-1.3) N=15 |
0.005 |
90.7 |
4.8 (1.1-21.6) |
0.220 |
| Orosomucoid (α1-acid glycoprotein) 1,2 g/l | 2.0 (1.6-2.6) N=43 | 1.5(1.0-1.7) N=15 |
0.005 |
95.3 |
10.3 (1.73-60,8) |
0.224 |
| Albumin 32-55 g/l | 33 (29-36) N=92 | 38 (34-42) N=41 |
<0.001 |
a43.6 |
4.7 (1.8-12.2) |
0.774 |
| IL-6 8 ng/l | 22.5 (7.0-42.3) N=90 | 7 (1.0-16.5) N=30 |
0.002 |
71.1 |
1.8 (0.8-3.95) |
0.440 |
| ESR F 21; M15 mm/h | 81 (58-105) N=95 | 44 (25.7-66.3) N=42 |
<0.001 |
97.9 |
9.3 (1.84-46.9) |
0.212 |
| Leukocytes 10*109 /l | 9.2 (7.3-11.1) N=95 | 8.1 (6.8-9.7) N=42 |
0.041 |
38.9 |
2.7 (1.1-6,5) |
0.477 |
| Trombocytes 360*109 /l | 362 (291-443) N=95 | 263 (217-346) N=42 |
<0.001 |
57.9 |
3.8 (1.7-8.6) |
0.106 |
| PCT 0.5 µg/l | 0.08 (0.04-0.01) N=56 | 0.07 (0.04-0.11) N=17 |
0.901 |
3.6 |
/ |
/ |
a–positives have lower albumin serum concentration than 32 g/l
To cite this abstract in AMA style:
Burja B, Lakota K, Kuret T, Žigon P, Jese R, Tomsic M, Rotar Z, Praprotnik S, Svec T, Čučnik S, Sodin Semrl S, Hocevar A. Utilization of Multiple Acute Phase Proteins and Biomarkers for Giant Cell Arteritis – Insight into Diagnosis and Clinical Complications [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/utilization-of-multiple-acute-phase-proteins-and-biomarkers-for-giant-cell-arteritis-insight-into-diagnosis-and-clinical-complications/. Accessed .« Back to 2016 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/utilization-of-multiple-acute-phase-proteins-and-biomarkers-for-giant-cell-arteritis-insight-into-diagnosis-and-clinical-complications/