Session Information
Session Title: Innate Immunity and Rheumatic Disease: Signaling Mechanisms
Session Type: Abstract Submissions (ACR)
Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease where the Complement System plays a key role in the pathogenesis. The objective of this pilot study was to measure the levels of the pattern recognition molecules of the Lectin Pathway: mannan binding lectin (MBL), collectin-L1 (CL-L1), and the three ficolins in plasma of patients with SLE and compare the plasma levels to a group of age and gender matched healthy controls. Further, we analyzed for associations between the plasma levels and SLE disease activity score and characteristic SLE manifestations.
Methods
Plasma was obtained from a cross-sectional cohort of 58 SLE patients. We collected prospectively demographic and clinical data including ACR classification criteria and SLE disease activity index score (SLEDAI). For comparison, blood samples were collected from 65 age and gender matched healthy blood donors. Plasma levels of MBL, CL-L1, M-ficolin (Ficolin-1) and H-ficolin (Ficolin-3) were measured using Time Resolved Immuno-Flourometric Assay (TRIFMA) developed at our own lab. Plasma levels of L-ficolin (Ficolin-2) were measured by ELISA (Hycult Biotech¨, the Netherlands). Mann-Whitney test were used for comparison of plasma levels of the proteins in patients and controls and Spearman correlation analysis was used for correlation analysis. p values < 0.05 were considered statistically significant.
Results
|
RESULTS
|
SLE Patients (n=58) Mean plasma conc. ng/ml (SD)
|
Healthy Controls (n=65) Mean plasma conc. ng/ml (SD)
|
Difference between means ng/ml (SD)
|
Mann-Whitney P value
|
|
MBL
|
1003(±821) |
1137(±1157) |
219,5 ± 183,5 |
0,5204 |
|
CL-L1
|
771(±145) |
937(±191) |
165,5 ± 30,84 |
< 0,0001 |
|
M-ficolin
|
356(±231) |
564(±266) |
214,1 ± 46,96 |
< 0,0001 |
|
L-ficolin
|
2649(±1031) |
2554(±998) |
94,97 (± 192,5) |
0,6116 |
|
H-ficolin
|
23998 (±10397) |
16387(±4927) |
7611 (± 1450) |
<0,0001 |
Mean plasma levels of CL-L1 and M-ficolin were significantly lower and H-ficolin significantly higher in patients with SLE compared to healthy controls (p<0.0001). A statistical significant difference between plasma levels of H-ficolin in SLE patients with lymphopenia compared to the non-lymphopenic patients was found (p=0.0434). A relatively higher level of CL-L1 in the subgroup of SLE patients with discoid rash was statistically significant (p=0.0364). Otherwise, analysis showed no statistically significant association between characteristic disease manifestations or SLEDAI score on one side and plasma level of MBL, CL-L1, M-ficolin, L-ficolin and H-ficolin on the other hand.
Conclusion
The plasma concentrations of several of the pattern recognition molecules of the Lectin Pathway were significantly altered in a cross-sectional co-hort of SLE-patients showing low levels of CL-L1 and M-ficolin and high levels of H-ficolin. In the subgroup of patients with lymphopenia, this manifestation was associated with a high level of H-ficolin. The association with a key element of the clinical picture, lymphopenia, may indicate a pathogenic role of Ficolin-3 in SLE.
A limitation of the study is small SLE subgroups.
Disclosure:
A. Troldborg,
None;
S. Thiel,
None;
M. J. Laska,
None;
B. Deleuran,
None;
J. C. Jensenius,
None;
K. Stengaard-Pedersen,
None.
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