Background/Purpose:

Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) are related systemic autoimmune diseases associated with proinflammatory prothrombotic biomarkers/cytokine (PPM) and antiphospholipid antibodies (aPL). Reports also suggest that low 25-hydroxy vitamin D (25OH-VD) levels are associated with disease activity in SLE. There is an increased prevalence and severity of SLE in Black and Afro-Caribbean patients (pts) but few data highlighting 25OH-VD and PPM levels in this population. We sought to determine which cytokines and oxidative stress markers are elevated in a unique population of Jamaican (JA) SLE pts.

Methods:

A total of 47 patients (mean age 43.3 ± 11.9yrs) satisfied ACR classification criteria for definite or incomplete SLE; the BILAG index was used to measure disease activity. Two groups of controls served as comparison for PPM. ELISAs were used to measure anti-dsDNA, aPL (anticardiolipin (aCL), anti-β₂-glycoproteinI (aβ₂GPI) and APhL®), 25OH-VD, IgG anti-oxLDL/β₂GPI antibodies (IgG aOXLβ-Ab) and oxLDL/β2GPI antigen-complex (OXLβ-Ag). Interferon (IFN)-α, Interleukin (IL)1b, IL6, IL8, inducible protein (IP)10, tumor necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF), and soluble CD40 ligand (sCD40L) levels were determined by the MILLIPLEXMAP human cytokine/chemokine assay in the serum of patients and controls. Pearson’s correlation and the Kruskal-Wallis test were used to evaluate PPM levels in SLE patients and controls.

Results:

A third of patients (14/47,29.8%) had at least one positive aPL and 5/47 (10.6%) had isolated IgA anti-β2GPI positivity. Most PPM were significantly elevated in SLE patients vs controls (Table 1). Only 6.4% (3/47) patients had positive IgG aOXLβ Ab levels but all of these patients had extremely elevated aPL. IgG aOXLβ Ab was significantly correlated with IgG aCL (r0.854, p<0.001), IgG APHL (r0.940, p<0.001) and IgG aβ₂GPI (r0.978, p<0.001) while OXLβ-Ag was associated with IgA aβ2GPI (r.316, p=0.031). Disease activity was significantly correlated with both dsDNA (r0.341, p=0.020) and IP10 (r0.362, p=0.013) and these 2 markers were also correlated (r0.490, p<0.001). Most patients (34/47, 72.3%) had below normal 25OH-VD levels and patients with 25OH-VD deficiency had higher mean IFN-α levels compared to those with normal levels (49.9 vs 3.6 pg/ml, p=0.05).

Conclusion:

Jamaican SLE patients have a high rate of aPL positivity, particularly IgA anti-β₂GPI, associated with oxidative stress markers and this may be an underlying reason for the increased prevalence of severe disease in Afro-Caribbean patients. IFN-inducible cytokines appeared to drive disease activity on the background of dsDNA activity, which is unsurprising. IFN activity was also associated with low 25OH-VD.

Table 1. Proinflammatory markers in SLE patients vs controls

Marker	JA SLE patients median	Controls median	P value
IL6 (pg/mL)	1.7	0.0	<0.001
IL1β (pg/mL)	0.0	0.0	0.108
TNFα (pg/mL)	7.1	0.0	<0.001
IP10 (pg/mL)	226.7	96.2	<0.001
sCD40L (pg/mL)	232.3	16.4	<0.001
IFNα (pg/mL)	4.5	0.0	0.162
VEGF (pg/mL)	154.6	88.3	0.031
OXLβ Ag (U/mL)	14.5	2.8	<0.001

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/characterization-of-a-jamaican-lupus-cohort-proinflammatory-biomarkers-and-disease-activity/