Neutrophil cytosolic factor 2 (NCF2) gene polymorphism is associated with juvenile-onset systemic lupus erythematosus, but probably not with other autoimmune rheumatic diseases in children.

BACKGROUND: Genetic variations of neutrophil cytosolic factor 2 (NCF2), a subunit of NADPH oxidase, are usually associated with chronic granulomatous disease, and their relationship with autoimmune disorders through the defective NADPH oxidase function during phagocytosis is suggested. Our study aimed to explore whether there is an association between the non-synonymous single nucleotide polymorphism in the NCF2 gene (rs17849502, NC_000001.11:g.183563445G>T) and the development of juvenile autoimmune rheumatic diseases. METHODS: In order to test this hypothesis, we conducted a pilot case-control study. In total, 709 children and adolescents, all Belarusians, were involved in the study including patients with juvenile-onset systemic lupus erythematosus (JSLE), juvenile idiopathic arthritis (JIA), Kawasaki disease (KD), and subjects without autoimmune and inflammatory diseases as the clinical control, as well as health newborns as the population control. Real-time polymerase chain reaction was used for genotyping. RESULTS: The minor T allele of NCF2 occurred most frequently in patients with JSLE (OR = 2.60, 95% CI = 1.18-5.73, p = 0.023 as compared to the clinical control). In groups with JIA and KD, its frequency did not differ from the control. The TT genotype was only observed in 5.7% of patients with JSLE (p = 0.007), but not in other groups. CONCLUSION: Therefore, our study suggested that NCF2 rs17849502 polymorphism is a potential genetic risk factor for JSLE, while it is probably not for such autoimmune rheumatic diseases as JIA or KD.

AGER gene variant as a risk factor for juvenile idiopathic arthritis.

BACKGROUND: The AGER gene encodes a cell surface multiligand receptor of advanced glycation end-products that is also capable of binding other molecules and is involved in numerous pathways related to inflammation, apoptosis, immunity and so on. In the present study, we aimed to investigate whether the AGER rs1035798 (G>A) intronic polymorphism, showing an association with multiple sclerosis and rheumatoid arthritis in adults, is related to juvenile idiopathic arthritis (JIA). METHODS: Caucasian children from the Belarusian population were enrolled in the study. In total, there were 201 cases with JIA, 37 with juvenile systemic lupus erythematosus, 222 children with the articular syndrome of non-autoimmune etiology (positive control for JIA) and 365 negative controls (children without any autoimmune or inflammatory diseases). Genomic DNA samples from the patients and controls were genotyped by a real-time polymerase chain reaction. RESULTS: A marked association of the homozygous AA rs1035798 genotype with JIA (p = 5 × 10-4 ) was found. Allele A was also associated with JIA (p = 0.0058), as well as with the articular syndrome of non-autoimmune etiology (p = 0.0264). The highest frequencies of the AA genotype were found in the subgroups of JIA patients with polyarthritis or severe oligoarthritis. The AA genotype patients also had the smallest mean age of the JIA onset. CONCLUSIONS: Our results demonstrate that the AGER rs1035798 AA genotype is a risk factor for JIA in Belarusian children. They also suggest a link between the AGER AA genotype and the risk of JIA early onset and severity. However, the functional relevance of the rs1035798 polymorphism is still unclear.

Polymorphism of Proteasomal Genes Can Be a Risk Factor for Systemic Autoimmune Diseases in Children.

The study aimed to assess the involvement of three proteasomal genes, PSMA6 , PSMC6 , and PSMA3 , in autoimmune pathogenesis by analyzing associations between single nucleotide polymorphisms and systemic rheumatic diseases with a different autoimmune component: juvenile idiopathic arthritis (JIA), the juvenile form of systemic lupus erythematosus, and Kawasaki's disease (KD). Our results showed that the PSMA6 (rs1048990) polymorphism can be a risk factor for JIA (false discovery rate q ≤ 0.090), while PSMA3 (rs2348071) has a tendency to be nonspecific and is shared with JIA and other autoimmune diseases, including KD, an illness with very low autoimmune activity and high autoinflammation.

Demographics of paediatric renal replacement therapy in Europe: a report of the ESPN/ERA-EDTA registry.

BACKGROUND: The ESPN/ERA-EDTA Registry collects data on European children with end-stage renal disease receiving renal replacement therapy (RRT) who are listed on national and regional renal registries in Europe. In this paper we report on the analysis of demographic data collected from 2009 to 2011. METHODS: Data on primary renal disease, incidence, prevalence, 4-year survival, transplantation rate and causes of death in paediatric patients receiving RRT were extracted from the ESPN/ERA-EDTA Registry for 37 European countries. RESULTS: The incidence of RRT in paediatric patients in Europe during the study period was 5.5 cases per million age-related population (pmarp) in patients aged 0-14 years and varied markedly between countries (interquartile range 3.4-7.0 years). The prevalence of RRT was 27.9 pmarp and increased with age, with 67 % of prevalent patients living with a functioning graft. The probability of receiving a transplant within 4 years was 76.9 % and was lowest in patients aged 0-4 years (68.9 %). Mortality in paediatric patients treated with RRT was 55-fold higher than that of the general EU paediatric population. Overall survival at 4 years was 93.7 %, with the poorest survival in patients aged 0-4 years and in patients starting on dialysis. Infections (19.9 %) were the primary cause of death in European paediatric RRT patients. CONCLUSION: Considerable variation exists in the current demographics of children treated with RRT across Europe.

Autoantibodies against complement C1q in acute post-streptococcal glomerulonephritis.

Autoantibodies against complement C1q (anti-C1q) strongly correlate with the occurrence of severe lupus nephritis. Recent data suggest that anti-C1q might also correlate with more severe forms of acute post-streptococcal glomerulonephritis (APSGN). Therefore, we prospectively investigated the role of anti-C1q in 50 children with newly diagnosed APSGN. Associations between anti-C1q and disease manifestations as well as serum complement concentrations were analyzed. Nineteen of the 50 children (38%) with APSGN were positive for anti-C1q compared to 0/40 healthy controls. Levels of anti-C1q correlated negatively with serum C1q and C3 concentrations. Anti-C1q positive patients had significantly higher proteinuria and serum creatinine as well as more often oliguria, hypertension and delayed resolution of the disease than patients without anti-C1q. The data point to a potential pathogenic role of anti-C1q in APSGN. Determination of anti-C1q might help to identify patients at risk for prolonged courses of the disease.

Clinical value of autoantibodies against C1q in children with glomerulonephritis.

OBJECTIVE: Autoantibodies against C1q (anti-C1q) have been found in a number of autoimmune and renal diseases. They are best described in adult patients with systemic lupus erythematosus, where a strong correlation between the occurrence of anti-C1q and severe lupus nephritis (LN) has been observed. However, the role of anti-C1q in children with systemic lupus erythematosus has not yet been determined. Furthermore, the clinical importance of anti-C1q in other forms of glomerulonephritis remains to be elucidated. The aim of this study was to investigate anti-C1q in children with different forms of glomerulonephritis including LN. METHODS: We prospectively investigated 112 children with different forms of newly diagnosed glomerulonephritis for the presence of anti-C1q by an enzyme-linked immunosorbent assay and compared them with healthy controls. Associations between anti-C1q and disease manifestations at the time of the measurements and during follow-up were investigated. RESULTS: Twenty-one of 112 patients were positive for anti-C1q compared with 0 of 40 healthy controls. Anti-C1q was associated with activity in LN and with disease severity in patients with acute poststreptococcal glomerulonephritis (APSGN). In LN, 7 of 12 patients were found to be anti-C1q positive. Six of these 7 had active disease at the time of the serum sampling compared with 1 of 5 of the anti-C1q-negative children. In children with APSGN, 8 of 24 were positive for anti-C1q. Anti-C1q-positive APSGN patients had significantly higher proteinuria and more often hypertension than those without anti-C1q. All 4 patients in which APSGN did not resolve spontaneously were anti-C1q positive. CONCLUSIONS: Anti-C1q is associated with active LN in children. In addition, children with anti-C1q-positive APSGN have more severe disease than those who are anti-C1q negative. These data suggest APSGN is another disease in which anti-C1q has a pathogenic role.