Gene polymorphism and HLA-G expression in patients with childhood-onset systemic lupus erythematosus: A pilot study.

Human leukocyte antigen-G (HLA-G) presents inhibitory functions in immune cells and is located in a chromosomal region associated with systemic lupus erythematosus (SLE) susceptibility. Polymorphisms in 3' untranslated region (3'UTR) of HLA-G gene may influence protein expression. To date, no study analyzing HLA-G polymorphism and expression in childhood-onset systemic lupus erythematosus (cSLE) has been conducted. Therefore, we investigated the influence of HLA-G 3'UTR polymorphisms in 50 cSLE patients and 144 healthy controls. For the expression analysis, the control group included 26 healthy individuals. No significant difference in allele, genotype, and haplotype frequencies was observed between patients and control group. However, both the 14 bp deletion allele (odds ratio [OR] = 2.76, 95% confidence interval [CI] = 1.17-6.52, P = .028) and the 14 bp deletion-deletion genotype (OR = 8.00, 95% CI = 1.57-40.65, P = .006) showed an association with lupus nephritis. After Bonferroni correction, none P-value remained statistically significant. Regarding HLA-G expression, no significant difference was observed between plasma levels of cSLE patients (56.02 U/mL, interquartile range [IQR] = 37.54-75.41) and control group (49.2 U/mL, IQR = 27.84-154.4, P = .952). However, when the patients were stratified according to clinical manifestations, patients with hematological manifestations showed a lower plasma concentration of soluble HLA-G (sHLA-G) (47.08 U/mL, IQR = 34.15-61.56) than patients with no hematological manifestations (65.26 U/mL, IQR = 47.69-102.60, P = .013). These results suggest that HLA-G polymorphism has small effect on cSLE susceptibility and that sHLA-G may be involved in the pathogenesis of the disease.

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study.

Childhood-onset systemic lupus erythematosus (cSLE) exhibits an aggressive clinical phenotype and severe complications. This could be due to a pro-inflammatory cytokine milieu. Therefore, we determined plasma levels of Th1 (IL-2, IFN-γ, TNF), Th2 (IL-4), Th17 (IL-17A, IL-6), and Treg (IL-10) cytokines in a cohort of cSLE patients and healthy controls, and we evaluated the association between these cytokines and disease activity. We conducted a cross-sectional study with 51 cSLE patients from two pediatric rheumatology services. Ten cSLE patients participated in a longitudinal follow-up study. Blood samples were collected from the same patient during active and inactive disease. Disease activity was evaluated according to SLE Disease Activity Index 2000 (SLEDAI-2K). Cytokines levels were measured by cytometric bead array technique. cSLE patients had higher IL-6 (P<0.001) and IL-10 (P<0.001) levels than healthy controls. Patients with active disease had higher IL-6 and IL-10 levels than patients with inactive disease (P=0.001 and P=0.014, respectively) and the control group (both P<0.001). IL-6 (P=0.022), IL-10 (P=0.013), and IL-17A (P=0.041) levels were significantly higher during active than inactive disease. Linear regression analysis revealed IL-6 (P=0.002, 95%CI=0.006-0.025) and IL-10 (P=0.01 95%CI=0.021-0.150) as independent factors for increased SLEDAI-2K. IL-6, IL-10, and IL-17A are candidate biomarkers for disease activity in cSLE patients. This is the first longitudinal study to support their pivotal role in the pathogenesis of the disease.

Cytokine profile in childhood-onset systemic lupus erythematosus: a cross-sectional and longitudinal study

Childhood-onset systemic lupus erythematosus (cSLE) exhibits an aggressive clinical phenotype and severe complications. This could be due to a pro-inflammatory cytokine milieu. Therefore, we determined plasma levels of Th1 (IL-2, IFN-γ, TNF), Th2 (IL-4), Th17 (IL-17A, IL-6), and Treg (IL-10) cytokines in a cohort of cSLE patients and healthy controls, and we evaluated the association between these cytokines and disease activity. We conducted a cross-sectional study with 51 cSLE patients from two pediatric rheumatology services. Ten cSLE patients participated in a longitudinal follow-up study. Blood samples were collected from the same patient during active and inactive disease. Disease activity was evaluated according to SLE Disease Activity Index 2000 (SLEDAI-2K). Cytokines levels were measured by cytometric bead array technique. cSLE patients had higher IL-6 (P<0.001) and IL-10 (P<0.001) levels than healthy controls. Patients with active disease had higher IL-6 and IL-10 levels than patients with inactive disease (P=0.001 and P=0.014, respectively) and the control group (both P<0.001). IL-6 (P=0.022), IL-10 (P=0.013), and IL-17A (P=0.041) levels were significantly higher during active than inactive disease. Linear regression analysis revealed IL-6 (P=0.002, 95%CI=0.006-0.025) and IL-10 (P=0.01 95%CI=0.021-0.150) as independent factors for increased SLEDAI-2K. IL-6, IL-10, and IL-17A are candidate biomarkers for disease activity in cSLE patients. This is the first longitudinal study to support their pivotal role in the pathogenesis of the disease.