Association of serum bilirubin and uric acid levels changes during neuroinflammation in patients with initial and relapsed demyelination attacks

Abstract

In order to examine the endogenous antioxidants values in the earliest phase of demyelination, we have determined bilirubin and uric acid (UA) serum values in the patients with clinically isolated syndrome (CIS) and relapsing remitting multiple sclerosis (RRMS), regarding their clinical disability, measured by Extended Disability Status Scale (EDSS), Magnetic Resonance Imaging (MRI), disease duration, gender and other parameters. The bilirubin and UA levels were lower in CIS and RRMS patients than in control group, whether male or female (p < 0.05). The bilirubin and UA levels were decreased in RRMS compared to CIS patients (p < 0.05). Regarding EDSS, MRI and disease duration, obtained values of bilirubin and UA were higher in both study groups in patients with lower EDSS, lower MRI lesion number and shorter disease duration (p < 0.05). The greatest significance in decreased bilirubin and UA levels was observed in female compared to male patients, in both study groups (p < 0.05). The results suggest negative linear correlation between bilirubin and UA levels and disease duration, EDSS and MRI in CIS (p < 0.01), with the same correlation between bilirubin and UA levels and disease duration in RRMS patients (p < 0.01). There was also significant correlation between bilirubin level and MRI findings and UA levels and EDSS in RRMS patients (p < 0.01). The obtained results point to the importance of endogenous antioxidants in the outbreak and course of neuroinflammation. This could be favorable for the new pathogenetically conditioned neuroinflammatory therapy concepts which do not initially rely only on immunomodulatory, but also on the antioxidative effects.

Uric acid: a potential biomarker of multiple sclerosis and of its disability

“…In particular, MS subjects with lower UA levels presented higher EDSS. This is in line with previous studies suggesting a relationship between UA levels and disease activity [8,14,17,18]. However, we did not include patients experiencing clinical relapses, and thus, our findings suggest an importance of UA levels in the outcomes of MS.…”

“…Accordingly, a recent meta-analysis supported the finding of lower serum UA levels in MS subjects [16], and large epidemiological surveys showed that conditions with pathologically increased UA levels (i.e., gout) and MS are almost mutually exclusive [3]. In addition, UA levels have been related to clinical relapses and neuroradiological activity, raising the hypothesis of UA taking part in MS progression [8,14,17,18]. As a consequence, the UA metabolic pathway has been suggested as a possible target of MS treatments.…”

“…The main inclusion criterion was a diagnosis of definite MS according to Poser or McDonald criteria [33,34]. We excluded subjects presenting MS-related conditions, such as current clinical relapse (defined as newly developing symptoms or reactivation of pre-existing deficits for a minimum of 24 h occurring at least 30 days after the preceding episode, in the absence of increased body temperature or infections) [18], recent DMT change ( < 6 months) [19], or recent corticosteroid treatment ( < 1 month) [20], possibly affecting serum UA levels or clinical evaluation. The clinical course of MS was defined according to Lublin and Reingold's classification [35].…”

Serum Bilirubin and Albumin in Anti-<b><i>N</i></b>-Methyl-D-Aspartate Receptor Encephalitis

“…It has been shown that low levels of serum bilirubin and albumin are associated with a variety of autoimmune disorders, such as multiple sclerosis [14], neuromyelitis optica [15], myasthenia gravis [16], and systemic lupus erythematosus [17]. Very recently, Jang et al [18] reported that serum albumin levels could predict the response to immune therapy in autoimmune encephalitis, suggesting an association between albumin and autoimmune encephalitis.…”

Relationship between Serum Uric Acid and Serum Oxidative Stress Markers in the Japanese General Population

“…This paradox may be due to the fact that UA cannot scavenge some radicals, such as superoxide [28], and/or that UA may function as a pro-oxidant, primarily within the cell, and as an antioxidant, primarily in plasma. On the other hand, UA may have a beneficial effect on bone metabolism; higher UA levels are associated with higher bone mass and a lower prevalence of vertebral fracture among healthy postmenopausal women [29], and there is a negative correlation between UA levels and disease duration and disability status in clinically isolated syndrome [30]. These observations suggest that elevated UA levels may be either harmful or protective in different contexts.…”