Background Glucocorticoids (GCs) and disease-modifying agents (DMARDs) are frequently used in the management of juvenile-onset Systemic Lupus Erythematosus (JSLE). Whilst affecting a range of immune cells including neutrophils, impact of these treatments on the dysregulated neutrophil apoptosis found in JSLE is unclear (1-3).
Objectives To investigate the potential influence of GC and DMARD treatment on JSLE neutrophil apoptosis.
Methods Neutrophil apoptosis in GC-treated (n=8), DMARD-treated (n=9), GC-non-treated (n=7), DMARD-non-treated (n=6) JSLE patients were compared to healthy controls (HC; n=15) using quantitative PCR to measure Mcl-1, XIAP (anti-apoptotic) and TRAIL (pro-apoptotic) gene expression relative to beta-2-microglobulin house-keeping gene. Ethical approval was in place.
Results Patients fulfilled American College of Rheumatology diagnostic criteria; mean total BILAG-2004 scores were 7.3; range 0-21 (GC-treated) and 4.6; range 0-21 (DMARD-treated). All GC-treated patients used Hydroxychloroquine (HCQ); six received concurrent DMARDs: Azathioprine (AZA, n=2), Mycophenolate Mofetil (MMF; n=2), Methotrexate (MTX; n=1) and AZA+MMF (n=1). Mean GC (prednisolone) dose was 33.6mg/day (range 5-60). DMARD-treated used: MMF+GC+HCQ (n=2), AZA+GC+HCQ (n=2), AZA+HCQ (n=2), MMF+HCQ (n=1), MTX+GC+HCQ (n=1) and MMF+AZA+GC+HCQ (n=1). GC-non-treated used HCQ (n=2), HCQ+AZA (n=2), HCQ+MMF (n=1) or nothing (n=2). DMARD-non-treated used HCQ (n=2), HCQ+GC (n=2) or nothing (n=2).
No statistically significant difference was found between GC-treated (0.67±0.18; 6.84±3.21; 0.51±0.13) and GC-non-treated (0.65±0.21, p=0.65; 1.44±0.84, p=0.06; 0.37±0.16, p=0.37); DMARD-treated (0.85±0.18; 3.49±1.66; 0.53±0.12) and DMARD-non-treated (0.4±0.13, p=0.12; 5.57±4.09, p=0.56; 0.33±0.17, p=0.09) for Mcl-1, XIAP or TRAIL in JSLE patients.
HCs (1.20±0.47; 3.49±1.95; 0.57±0.16) did not differ statistically significantly in gene expression from either GC-treated JSLE (p=0.97; p=0.25; p=0.77) or DMARD-treated JSLE patients (p=0.48; p=0.57; p=0.56).
Overall, no statistically significant difference in mRNA expression was found between the groups: GC-treated, GC-non-treated and HC; or between DMARD-treated, DMARD-non-treated and HCs for any of the genes analysed (p>0.05). Also, GC-treated JSLE patients did not differ statistically significantly from DMARD-treated JSLE patients in gene expression (p=0.52, p=0.44, p=0.67).
Conclusions Literature demonstrates JSLE and GC individually can affect neutrophil apoptosis. Both GC and DMARDs have a variety of effects on immune cells including neutrophil function. We found no statistically significant difference between GC-treated JSLE, GC-non-treated JSLE and HCs; DMARD-treated JSLE, DMARD-non-treated JSLE and HCs; or GC-treated and DMARD-treated JSLE patients. This study highlights important issues, including the potential impact of the combination of disease related immunological changes in JSLE and concurrent use of single or multiple medication, and therefore the importance of careful translation of laboratory findings to clinical practice.
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Wright, H.L et al. Annals of the Rheumatic Diseases 2011:70(3):537-543.
Disclosure of Interest None Declared
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