Session Information
Date: Sunday, November 8, 2015
Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Urinary biomarkers have a potential for identification, follow-up and assessment of response to treatment in patients with lupus nephritis. Urinary proteomics can help in identification of new biomarkers. Thus we have used urinary proteomics in order to identify proteins that are seen uniquely in patients with active lupus nephritis.
Methods: Urine samples from patients with active and inactive lupus (SLEDAI<4) were collected, spun and immediately frozen at -80°C. After protein extraction, 2D gels were run followed by MALDI-TOF-TOF of the differentially expressed spots in urine from patients with active nephritis to identify the proteins. Biomarkers identified were measured by ELISA in a large group of patients as well as in urine samples from healthy control, RA and diabetes with proteinuria. In addition patients with active nephritis were followed up and samples collected at 6 and 12 months. Disease assessment was done using SLEDAI. All urinary values were normalized to creatinine excretion. Non-parametric tests were used for analysis
Results: There were 88 patients with SLE (Table) and 20 each of healthy controls, RA and diabetes. In addition samples from 33 patients with active nephritis at 0 and 6 months from 2 different centers were also used for validation.
Among the many spots that were differentially expressed in active lupus nephritis as compared to inactive lupus and healthy control, three were selected and identified as retinol binding protein (RBP), alpha-1-antichymotrypsin (AAC) and haptoglobin (HAP).
Table. Clinical and laboratory parameters of SLE patients (cross sectional analysis)
|
|
Active Nephritis |
Active Non-Renal |
Inactive Disease |
|
Number |
45 |
24 |
19 |
|
F:M |
56:2 |
19:5 |
38:1 |
|
Median age in years |
27 (12 – 50) |
28.5 (15 – 50) |
28 (14 – 48) |
|
rSLEDAI |
8 (4-16) |
0(0) |
0 (0) |
|
SLEDAI |
18 (6-28) |
10 (5-20) |
0 (0-4) |
|
C3 (mg/dl) |
48.5 (16.9 – 125) |
66.7 (17.3 – 163) |
117 (34.2 – 194) |
|
C4 (mg/dl) |
7.8 (5.3 – 55.7) |
11.05 (5.3 – 32.2) |
24.15 (5.6 – 44.7) |
|
Anti-ds DNA (IU) |
200 (13 – >300) |
185(<6.25 – >300) |
44 (<6.25 – 200) |
|
Urinary protein/creatinine ratio |
3.22 (0.12 – 8) |
0 (0 – 1.45) |
0 (0 – 0.87) |
|
Serum Creatinine (mg/dl) |
0.9 (0.4 – 3.87) |
0.82 (0.4 – 1.4) |
0.8 (0.4 – 1.3) |
|
Normalized RBP |
0 (0 – 0.75) |
0 (0 – 0.21)** |
0 (0 – 0.29)* |
|
Normalized AAC |
8.67 (1.4-33.7) |
1.65 (.06 – 13.2)** |
0.4 (0.08 – 52.7)** |
|
Normalized HAP |
2.79 (0.02 – 3.8) |
0 (0 – 5.4)** |
0 (0 – 2.06)** |
p-value *= <0.05 ,**= <0.001 as compared to active nephritis group.
On validation, RBP levels were higher in patients with active lupus nephritis as compared to other groups (Table 1; p<0.05) except patient with diabetes. The urinary levels had good correlation with renal SLEDAI (r=0.284; p<0.008) and SLEDAI(r=0.316; p<0.003).On longitudinal study the levels normalized in majority at 6 and 12 months (p<0.01).
AAC levels were much higher in patients with active nephritis as compared to all other groups (Table ; p<0.001) including diabetics. The urinary levels had moderate correlation with renal SLEDAI(r=0.577; p<0.001) and SLEDAI (r=0.461; p<0.001). On follow up the levels reduced at 6 and 12 months (p<0.01).
Haptoglobin levels were more than 10 fold higher than other groups (Table 1; p<0.001). HAP levels also correlated well with renal SLEDAI (r=0.594; p<0.001) and SLEDAI (r=0.371; p<0.001). In majority the levels fell at 6 and 12 months (p<0.001).
A patient who developed ESRD at 6 months had persistently high levels of all three biomarkers. In the second set of samples of active nephritis all the three biomarkers had a significant fall at 6 months (n=33) (p<0.001) as compared to baseline.
Conclusion: Haptoglobin, retinol binding protein and alpha-1 anti-chymotrypsin are potential biomarkers for lupus nephritis activity.
To cite this abstract in AMA style:
Aggarwal A, sinha S, Gupta R, Rajasekhar L, Yadav A, Misra R, Negi V. Urinary Proteomics Identifies Three Novel Biomarkers for Lupus Nephritis Activity: Retinol Binding Protein, Alpha-1-Antichymotrysin and Haptoglobin [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/urinary-proteomics-identifies-three-novel-biomarkers-for-lupus-nephritis-activity-retinol-binding-protein-alpha-1-antichymotrysin-and-haptoglobin/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/urinary-proteomics-identifies-three-novel-biomarkers-for-lupus-nephritis-activity-retinol-binding-protein-alpha-1-antichymotrysin-and-haptoglobin/