Hyperhomocysteinemia in children with juvenile idiopathic arthritis is not influenced by methotrexate treatment and folic acid supplementation: A pilot study
ABSTRACT Our first objective was to compare plasma total homocysteine (tHcy) concentrations in juvenile idiopathic arthritis (JIA) patients requiring methotrexate (MTX) treatment and healthy children. Our second aim was to evaluate the influence of low-dose (10-15 mg/m2/week) MTX treatment combined with folic acid supplementation (1 mg/d) or placebo on tHcy concentrations in JIA patients.
In 17 JIA patients and 17 age- and sex-matched healthy children, baseline tHcy concentrations were measured. When MTX treatment was initiated, JIA patients were randomly assigned to folic acid 1 mg/d/p.o. followed by placebo (8 weeks each) or vice versa. Blood samples for measurement of tHcy, vitamin B6, B12 and folate were taken after 4 weeks, 12 weeks and 20 weeks of treatment.
1) In the healthy children the mean tHcy concentration was 6.3 +/- 1.68 mumol/l as compared to 9.99 +/- 5.17 mumol/l in JIA patients (p < 0.04). At baseline, 5/17 JIA patients had tHcy concentrations > 10.5 mumol/l, the 99th percentile for teenagers. 3/5 patients even exceeded the upper normal level for adults (tHcy > or = 15 mumol/l). MTX treatment did not result in a significant increase of tHcy and folic acid supplementation had no significant impact on tHcy levels.
This pilot study shows that patients with JIA requiring MTX treatment have significantly elevated baseline plasma tHcy concentrations compared to age- and sex-matched healthy controls. No significant impact of MTX and folate supplementation on tHcy concentration was found.
- SourceAvailable from: Luciano Galdieri
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- "Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease in which clinical manifestations may persist for decades in some patients despite adequate treatment . There are two studies about the level of Hcy in children with JIA and the results have been conflicting [7,8]. Huemer  et al evaluated Hcy levels in 17 patients with JIA using methotrexate (MTX) with or without folic acid supplementation and in controls matched for age and gender. "
ABSTRACT: An increased concentration of plasma homocysteine (Hcy) has toxic effects on vascular endothelium. This seems to be a risk factor of cardiovascular disease, premature stroke and venous thrombosis. The risk is higher in coincidence with other factors like chronic diseases and familiar hypercholesterolemia. The aim of our study was to evaluate plasma Hcy concentration in patients with juvenile idiopathic arthritis (JIA) and its correlation with methotrexate (MTX) therapy, serum folate and B12 vitamin, and hyperlipidemia. Fifty-one patients (37 females; mean age 11.3 years, range 2.3-17 years) with JIA and 52 healthy controls (42 females; mean age 12.5 years; range 3-18 years) were included in the study. Thirty-two patients were using weekly MTX (mean doses: 0.1-1 mg/kg). For statistical analysis both JIA and control groups were distributed in three subgroups according to age (3 - 7, 8 - 12 and 13 - 18 years). The laboratory investigation included measurement of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasma Hcy, serum folate, vitamin B12, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). For data analysis, we considered raised Hcy values >or= 12.56 micromol/L, which corresponds to the 90th percentile observed in the control group. The mean plasma Hcy concentration was 9.3 +/- 3.16 micromol/L in JIA patients and 8.9 +/- 2.42 micromol/L in healthy controls (p = 0.615). Higher concentration of Hcy was observed in the subgroup of 13 - 18 years (patients and controls, p < 0.001). We did not find correlation between MTX use and plasma Hcy concentration. With regard to vitamin B12 concentration, we detected normal values in both patients and controls while serum folate concentration was higher in patients (p < 0.001). With regard to the lipidogram, lower concentration of HDL was found in patients (p = 0.007) and higher levels of VLDL (p = 0.014) and triglycerides (p = 0.001) were observed in controls. We did not observe correlation among plasma Hcy concentration, clinical findings, ESR and CRP. JIA patients do not present significant increased concentration of Hcy despite the use of MTX, probably due to the folate supplementation. The mild abnormalities in the lipidogram may reflect a current concern with diet and health.Pediatric Rheumatology 04/2007; 5(1):2. DOI:10.1186/1546-0096-5-2 · 1.61 Impact Factor
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ABSTRACT: Whole blood samples of known methylene tetrahydrofolate reductase (MTHFR) genotypes from 24 individuals were examined at site C677T. Their amplified DNA products were assessed by two-color fluorescence cross-correlation measurements and agarose gel electrophoresis/capillary gel electrophoresis. DNA subpopulations were identified which were not associated with the proper genotype by primer combinations and cycling conditions called multiplexes. We confirmed that DNA analysis by two-color fluorescence cross-correlation measurements allowed the detection of fluorescence signals specifically associated with the proper genotypes in a mixture of amplified nontarget DNA molecules without DNA sizing. The measurement approach does not require complex, follow-up mathematical analysis and is applicable to any single nucleotide polymorphisms. The simple immunogenetic model showed how the approach works to reveal specific DNA target by preventing detection of nontarget DNA. Under those experimental conditions, a new ultrasensitive, and specific method for clinical immunologists is born.Experimental and Molecular Pathology 07/2004; 76(3):212-8. DOI:10.1016/j.yexmp.2003.12.007 · 2.71 Impact Factor
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ABSTRACT: The pediatric arthritides encompass the seven types of juvenile idiopathic arthritis (JIA) (formerly known as juvenile rheumatoid arthritis and juvenile chronic arthritis) as well as granulomatous arthritis caused by pediatric sarcoid, or by Blau syndrome. Many of the recent studies on pathogenesis have simply divided patients into three categories: oligoarthritis, polyarthritis, and systemic arthritis. Where the existing data allow, this article uses the approved Durban criteria (Box 1) . In many cases, however, the older data do not reflect the more recent understanding of the clinical subsets. Pediatric arthritides are both similar and distinct from adult-onset arthritides. For example, spondyloarthropathies and rheumatoid arthritis may present in childhood. The course of rheumatoid factor-positive JIA proceeds in childhood in a manner similar to rheumatoid arthritis seen in adults , whereas the spondyloarthropathies have a course that is marked by increased extra-axial symptoms and modest sacroiliitis compared with adults . The other types of JIA are unique to children. Recent studies have begun to expose the distinct types of inflammation occurring in these disorders.Pediatric Clinics of North America 04/2005; 52(2):335-+. DOI:10.1016/j.pcl.2005.01.002 · 2.12 Impact Factor