Variation of serum uric acid levels in multiple sclerosis during relapses and immunomodulatory treatment

Abstract

Uric acid (UA), a product of purine metabolism, may be an antioxidant, perhaps acting as a scavenger of peroxynitrite. Patients with gout have a reduced incidence of multiple sclerosis (MS). A number of studies found that patients with MS have low serum levels of UA, although it has not been established whether this represents a primary deficit or a secondary effect. UA has also been proposed as a marker of disease activity and response to immunosuppressive or immunomodulatory treatment. We retrospectively reviewed 83 relapsing-remitting or secondary progressive MS patients (64 females and 19 males) followed in our Neurology Unit. We collected data concerning demographic variables as age and sex, and clinical variables as age of onset, clinical type, disease duration, EDSS score and total number of relapses. We considered UA levels in three different situations: during a relapse, during remission period and during remission period under immunomodulatory treatment [Interferon Beta 1a i.m. (Avonex; Biogen Idec Inc., Cambridge, MA, USA), Interferon Beta 1a s.c. (Rebif; Serono Europe Limited, London, UK), Interferon Beta 1b (Betaferon; Bayer Schering Pharma AG, Berlin, Germany) or Glatiramer Acetate (Copaxone; TEVA Neuroscience LLC, Kansas City, MO, USA)]. A Wilcoxon matched pairs test was carried out to determine differences between groups. A P-value less than 0.05 was considered statistically significant. In 33 patients, we were able to compare at least one UA value obtained during a relapse with at least one when remission without treatment. Mean serum UA levels were significantly lower when measured during a relapse (r: 0.39, P: 0.024). In 27 cases, we compared at least one remission value without treatment with at least one obtained during remission and immunomodulatory treatment. Mean serum UA levels significantly increased when determined during Interferon Beta or Glatiramer Acetate therapy (r: 0.84, P < 0.001). Although we do not know exactly whether and how UA is involved in MS pathogenesis, our data suggest that UA might reflect disease activity or treatment response in MS.

Serum uric acid levels in patients with multiple sclerosis: a meta-analysis

“…Three studies were published in Chinese, while others were in English. Three studies [14][15][16] were excluded due to no original data reported, while another three studies [17][18][19] were excluded because they were reviews. For consistency, we included studies of only case-control design.…”

“…8,11,22,23 In this review, we have also demonstrated a trend towards serum UA levels were lower in patients with MS than in healthy controls and OINDs. Serum UA levels were inverse correlation with MS. On the basis of these findings, we could speculate that lower serum UA reserve is possibly an early pathogenic mechanism in MS. Additionally, the pathogenetic role of UA in MS is also supported by data showing the significant increase in serum UA in patients receiving interferon-beta or glatiramer-acetate, which have been shown to reduce disease activity in MS. 24,25 It is generally accepted that lower serum UA in MS patients might be due to both intrinsically reduced antioxidant capacity and increased consumption of UA in MS. However, we have to admit the fact that the potential association between serum UA levels and the clinical status in MS is still unclear.…”

Low Serum Urate Levels Are Associated to Female Gender in Multiple Sclerosis Patients

“…The correlation between urate levels and clinical and paraclinical disease activity and disability has been also evaluated, with conflicting results [9], [11], [13], [15], [19], [21], [25], [26], [36] Consistently with the results of the metanalysis, [28] in our study serum urate did not correlate with disability level and disease duration, but lower urate levels were observed in female patients with higher disease activity (ARR) and in the early phases (CIS) of the MS. Based on these findings the contribute of inadequate protection against reactive oxygen and peroxynitrite by urate to the axonal loss and the clinical progression of the disease still remains uncertain, but a role of low urate in favouring neuroinflammation and demyelination that occur early in MS and mainly in females may be hypothesized.…”

Serum Uric Acid Levels in Patients with Relapsing-Remitting Multiple Sclerosis

“…Several studies showed lower levels of serum uric acid in MS patient s (7,11,22,23,25), and also Mattle et al (25) reported that uric acid levels were decreased in MS patients when compared to control subjects along with in patients with relapse were lower than in patients in remission. Serum UA levels were lower in the mono-and dizygotic twins with MS than in the healthy twin (7).…”