Session Title: Systemic Lupus Erythematosus: Clinical Aspects
Session Type: Abstract Submissions (ACR)
Background/Purpose: B Lymphocyte Stimulator(BLyS) plays an important role in the pathogenesis of Systemic Lupus Erythematosus(SLE). Whilst trials of anti BLyS-targeted therapy have shown promise, the optimal timing and benefits of anti BLyS therapy remain undetermined. We sought to assess the relationship between BLyS levels, disease activity, damage scores and clinical profiles in Caucasian SLE patients.
Methods: BLyS levels were determined by ELISA. Elevated BLyS levels were defined as values above the 95% percentile in a cohort of healthy controls. Patients were enrolled only if they could confirm three generations of their family were of Irish descent. Patients with SLE were divided into two groups: those with elevated BLyS levels(Group 1) or normal BLyS levels(Group 2).Demographic data, disease activity as per SLEDAI and damage scores(SLICC) at 5 year follow-up were recorded. Categorical variables were analyzed using Fisher’s exact test and continuous variables by unpaired t-tests. The Mann-Whitney test was used in instances of non-normality.
Results: 45 patients were recruited.In this homogenous Caucasian population BLyS levels were higher in those with malar rash (920pg/ml v 594pg/ml,p< .05), musculoskeletal involvement (930pg/ml v 591pg/ml, p< .04), immunologic activity(1041pg/ml v 646pg/ml,p <.005) and renal disease (1127 pg/ml v 748pg/ml,p<.009).
In keeping with previous reports BLyS levels showed significant correlation with disease activity as measured by SLEDAI (r = .682, p<0.001). Twenty three SLE patients (51%) fell above the defined cutoff in healthy controls and were therefore classified as having “elevated” BLyS levels with the remaining twenty two patients having “normal” BLyS levels, the difference between groups being significant(1173 pg/ml v 558pg/ml,p<.001).
Patients with elevated BLyS levels at time of enrolment were found to be significantly younger at time of study visit (32.97 v 44.32 years, p<0.0019) with a shorter disease duration (4.96 v 9.23 years,p <0.0125). They also accrued significantly more damage over the subsequent five year period with a mean increase in damage score of 0.53 compared to 0.13 for patients with normal BLyS levels (p< 0.012). The odds ratio(OR) was 5.8 (p=0.023 by Fishers exact test). The change in SDI correlated significantly with plasma BLyS levels (r = .399,p<0.007). There was no difference in BLyS levels between those requiring steroid therapy to control their disease versus those steroid free. However, BLyS levels were higher in those patients requiring additional immunosuppression (Azathioprine or greater) to control their disease (926pg/ml v 642 pg/ml,p<0.005).
Sm antibody(OR 13.4,p=0.049), low C4(OR 8,p=.016) and dsDNA positivity(OR 6.1, p=0.007) predicted BLyS elevation.
Conclusion: BLyS levels are higher in younger patients and those with a shorter disease duration. Although further validation of these clinical and immunological associations are warranted in larger cohorts of genetically homogenous populations our study suggests BLyS blockade may be most beneficial if introduced early in disease in young patients in an effort to prevent damage. BLyS levels remain elevated despite the use of additional conventional immunosuppressive agents.
E. M. McCarthy,
J. Ni Gabhann,
D. G. Howard,
P. G. O’Connell,
G. M. Kearns,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/b-lymphocyte-stimulator-levels-are-higher-in-caucasian-sle-patients-earlier-in-disease-course-and-predict-damage-accumulation/