Cerebrospinal fluid fetuin-A is a biomarker of active multiple sclerosis.

BACKGROUND: There is an urgent need for biomarkers in multiple sclerosis (MS) that can reliably measure ongoing disease activity relative to inflammation, neurodegeneration, and demyelination/remyelination. Fetuin-A was recently identified as a potential biomarker in MS cerebrospinal fluid (CSF). Fetuin-A has diverse functions, including a role in immune pathways. OBJECTIVE: The objective of this research is to investigate whether fetuin-A is a direct indicator of disease activity. METHODS: We measured fetuin-A in CSF and plasma of patients with MS and correlated these findings to clinical disease activity and natalizumab response. Fetuin-A expression was characterized in MS brain tissue and in experimental autoimmune encephalomyelitis (EAE) mice. We also examined the pathogenic role of fetuin-A in EAE using fetuin-A-deficient mice. RESULTS: Elevated CSF fetuin-A correlated with disease activity in MS. In natalizumab-treated patients, CSF fetuin-A levels were reduced one year post-treatment, correlating with therapeutic response. Fetuin-A was markedly elevated in demyelinated lesions and in gray matter within MS brain tissue. Similarly, fetuin-A was elevated in degenerating neurons around demyelinated lesions in EAE. Fetuin-A-deficient mice demonstrated delayed onset and reduced severity of EAE symptoms. CONCLUSIONS: Our results show that CSF fetuin-A is a biomarker of disease activity and natalizumab response in MS. Neuronal expression of fetuin-A suggests that fetuin-A may play a pathological role in the disease process.

Detection and prevention of ocular phototoxicity of ciprofloxacin and other fluoroquinolone antibiotics.

Fluoroquinolone (FLQ) drugs are a potent family of antibiotics used to treat infections including ocular infections. To determine if these antibiotics may be phototoxic to the eye, we exposed human lens epithelial cells to 0.125-1 mm FLQs (ciprofloxacin [Cipro], lomefloxacin [Lome], norfloxacin [Nor] and ofloxacin [Ofl]), the precursor quinolone nalidixic acid (Nalid) and UVA radiation (2.5 J cm(-2)). Based on fluorescence confocal microscopy, FLQs are diffused throughout the cytoplasm and preferentially located in the lysosomes of lens epithelial cells. Neither FLQ exposure alone nor UVA exposure alone reduced cell viability. However, with exposure to UVA radiation the FLQs studied (Cipro, Nor, Lome and Ofl) induced a phototoxic reaction that included necrosis, apoptosis, loss of cell viability as measured by MTS, and membrane damage as determined by the lactate dehydrogenase assay. Both Nalid and all FLQs studied (Cipro, Nor, Lome and Ofl) photopolymerized the lens protein alpha-crystallin. Phototoxic damage to lens epithelial cells and/or alpha-crystallin will lead to a loss of transparency of the human lens. However, if precautions are taken to filter all UV radiation from the eye while taking these antibiotics, eye damage may be prevented.

Chronic myeloid leukemia associated with mitoxantrone treatment in a patient with MS.

We report the first case of chronic myeloid leukemia (CML) in a patient with multiple sclerosis (MS) diagnosed within two years of receiving mitoxantrone therapy. Previously only acute forms of leukemia particularly acute promyelocytic leukemia (APL) have been associated with mitoxantrone treatment in MS. This underscores the need for only using mitoxantrone in severe treatment-unresponsive cases of MS.