Peripheral chitotriosidase in patients with multiple sclerosis

Dear Editor, We read the paper from Dr Verbeek s and colleagues recently appeared in your Journal (1). The authors support elegantly some results of our (2) and Dr Czartoryska s and colleagues (3) works by finding that the production of chitotriosidase (CTTS) is increased in the central neurological compartment of patients with multiple sclerosis (MS), particularly in relation to markers of intrathecal inflammation. However, contrary to our (2) and Dr Comabella s (4) works, they found that the mean peripheral serum level of CTTS seems not to differ between MS, other neurological patients and healthy controls. To explain this difference from the existing literature, in their extensive discussion section, Dr Verbeek and colleagues took into account pathologic differences of MS lesions and clinical peculiarities of MS patients who refer to their MS centre. We think that such explanations are not sufficient to solve the discrepancy. In pathological conditions, peripheral CTTS activity is elevated both in acute and chronic systemic and neurological diseases that involve macrophage-microglia phagocyte ⁄ inflammatory activities. It is well established that the link between CTTS and neurological diseases is not limited to MS, as it extends from hyper-acute (ischemic stroke) up to slowly degenerative (Alzheimer s disease; reviewed in Ref. 5) conditions. Blood CTTS production is also influenced by physiological factors such as age and race (5). As another explanation, the authors claim that the potent attraction of benign or very mild MS cases (hypothetically bearing low peripheral CTTS levels) to their high-expertise MS Centre may decrease the average blood CTTS level of their whole MS cohort. However, the mean disability score at the time of lumbar puncture and blood drawing, reported on Table 3 (EDSS 3.6), seem to preclude this possibility. Based on well-known immunogenetic peculiarities of the Sardinian population, the authors also argued for a genetic difference between their and our MS patient series. However, a significantly higher CTTS serum level have been recently found also in Spanish MS patients (3). This makes a second ethnically-based difference rather unlikely. Most importantly to us, it seems that Dr Verbeek and colleagues have omitted to determine the CTTS peripheral activity on a properly large sample of a truly healthy control population. Their healthy control sample is composed of 55 hospitalised patients subjected to venous and lumbar puncture for unspecific or unspecified health problems. In our paper (2), prior to infer in favour of an increase of peripheral CTTS in the MS population sample, we determined plasma CTTS level on 309 healthy controls of the general population. We think that this unusual procedure for control recruitment, together with the littleness of the sample size, could have biased the average normal CTTS serum levels of healthy people. Furthermore, in their neurological controls (OND), the authors also included diseases that very likely may be accompanied by increased CTTS peripheral level (cerebrovascular diseases and adrenoleukodystrophy; Table 3). Overall, despite the extensive explanatory discussion, the otherwise accurate Verbeeks s paper raises many doubts on the actual normal serum CTTS level. As a final note, we also found criticisable that the pioneeristic work on the intrathecal CTTS expression by Dr Czartoryska s (3) has not been reminded by the authors in their reference list.