Background Elevated levels of B Lymphocyte Stimulator(BLyS) play an important role in the pathogenesis of Systemic Lupus Erythematosus. Although anti BLyS-targeted therapies have shown promise in the treatment of SLE, results of clinical trials highlight that a number of patients remain unresponsive to BLyS pathway blockade. The optimal timing of anti BLyS therapy remains to be determined.
Objectives To identify clinical, serologic and cytokine profiles that are associated with elevated BLyS levels in a homogenous Caucasian SLE population and thereby identify patient subtypes that are more likely to respond to BLyS blockade.
Methods BLyS levels in addition to a range of other proinflammatory cytokines were determined by ELISA. Elevated BLyS levels were defined as values above the 95% percentile in a cohort of normal healthy controls. For analysis patients with SLE (as per ACR criteria) were divided into two groups: those with elevated BLyS levels or normal BLyS levels. Clinical history, lab measures of disease activity and lupus-associated autoantibodies were recorded for all patients. 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. Spearman’s correlation coefficient was calculated for all cytokines assayed.
Results Twenty two patients were included in both groups. BLyS levels were significantly different (1173 pg/ml v 558 pg/ml, p<.001) between groups. Elevated BLyS levels failed to show correlation with any of the individual cytokines assayed. However in patients with elevated BLyS levels the strongest proinflammatory cytokine signatures were seen between IL-1 v IL-6 (r=0.84 p<0.001) and IL-6 v TNF(r=0.83 p<0.001).
Elevated levels of BLyS were seen in both younger patients (33.4yrs v 43.6 yrs, p<0.006) and in those that had a shorter disease duration (5 yrs v 8.95 yrs, p<0.02). Patients with elevated BLyS displayed a trend towards younger age at diagnosis(28.4 yrs v 34.7 yrs, p=0.07).
Patients with elevated BLyS were more likely to be dsDNA positive (p<0.05) and to demonstrate higher titres of dsDNA (232iu/ml v 121iu/ml,p<.01). The presence of Sm antibody significantly predicted elevated BLys levels (p<0.05, odds ratio 13.5). All other lupus autoantibodies recorded failed to predict BLyS elevation. Other laboratory measures of disease activity failed to differentiate between those with elevated and normal BLyS levels although there was a trend towards low complement in those with BLyS elevation (p=0.07).
BLyS levels were significantly higher in those with musculoskeletal involvement(930 pg/ml v 591 pg/ml, p<0.04) and malar rash (920 pg/ml v 594 pg/ml, p<0.05). Whilst there was no significant difference in the absolute number of patients with renal involvement between groups mean BLyS levels were higher in those with renal involvement (1126 pg/ml v 751 pg/ml).
Conclusions BLyS levels are higher in younger patients and those with shorter disease duration. Sm antibody and dsDNA positivity predict elevated levels of BLyS. BLyS blockade may be most beneficial if introduced early in the course of disease in young patients presenting with renal, musculoskeletal and skin disease with these autoantibody profiles.
Disclosure of Interest None Declared
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