The initial work by Codolo et al.employed the standardsubcutaneousvariant of the MB49 model of bladder cancer and injected HP-NAP near to the tumour site. article, Codolo et al. explained the anti-tumour action of theH. pyloriprotein and TLR-2 ligand, HP-NAP in a bladder malignancy model and elucidated the mechanisms of action as including Th1 responses. Th1 responses are known to be important for clinical responses to BCG-therapy [5,6], and it was to be expected that a successful response to other bacterial proteins would also be Th1-associated. In this regard, it has previously been shown that HP-NAP induces IL-12 secretion from DC and this is the likely mechanism for Th1-polarisation [7]. The initial work by Codolo et al.employed the standardsubcutaneousvariant of the MB49 model of bladder cancer and injected HP-NAP near to the tumour site. However, they went on to test HP-NAP in the more challenging yet physiological orthotopic model. Administration of HP-NAP reduced the rate of tumour growth, increased necrosis and reduced angiogenesis. Importantly, intravesical administration of HP-NAP was shown to be similarly effective to the current gold-standard immunotherapeutic, live BCG. The central tenet of the Kountouras et al.letter is the potential side effects of theH. pyloriprotein, HP-NAP. In support of their argument, the authors point out their letter in which data from a small clinical study (n= 29) show an association betweenH. pyloriinfection and multiple sclerosis (MS) [8]. They also research a larger study [9], which in contrast, shows identical levels ofH. pyloriseropositivity in MS patients and healthy controls. This study is usually cited as evidence that, possible cross-mimicry between HP-NAP and/or bacterial aquaporin (AQP) and neural tissues may be associated with the anti-AQP4 antibody related neural damage in MS. However, this paper specifically says that they were unable to demonstrate cross-reactivity, and it was outside the remit of the study carried out to explore experimentally whether HP-NAP antibodies reacted with central nervous system (CNS) tissues. The letter referenced in addition to this study [10] is usually a rebuttal of the Li study, presents no new data and says that, Molecular cross mimicry between HP-NAP and AQP4 is usually unlikely to be a responsible underlying mechanism. A search of the literature also discloses no evidence that there is either cross-reactivity between HP-NAP and AQP4 or reactivity between HP-NAP and the CNS. At the molecular level, TG 003 AQP4 is usually a water channel protein, expressed in astrocytes and at the interface between cellular and fluid compartments in the brain [11, 12] where it plays a role in water homoeostasis and the regulation of oedema. There may be an association between anti-AQP4 antibodies and MS, especially the opticospinal subtype, but given the lack of robust evidence for Rabbit Polyclonal to OR a link betweenH. pyloriand AQP4, the possible role of AQP4 in MS pathophysiology is usually irrelevant to the paper under conversation. In contrast to the Gavalas study, a body of epidemiological evidence supports the hypothesis of a protective link betweenH. pyloriinfection and MS [1315]. In the work of Li et al. in 105 consecutively recruited MS patients, the TG 003 incidence ofH. pyloriseropositivity was significantly lower in MS patients than in controls [13]. Furthermore,H. pyloriseropositivity showed an inverse correlation with disease severity in MS patients. Work by Wender in a group of 90 patients also showed the absence of causative effect betweenH. pyloriinfection and MS [14]. Radic and co-workers undertook a literature-based examination of the relationship betweenH. pyloriinfection and systemic sclerosis, a complex and rare autoimmune disorder [15]. Their conclusion was that whilstH. pylorimay play a role in the pathogenesis of systemic sclerosis, it may also protect against MS and other autoimmune diseases. Returning to the intravesical setting and the potential use ofH. pyloriproteins in bladder malignancy, it is unlikely that this TG 003 administration of HP-NAP will TG 003 lead to efficient systemic immunisation through this route. It would seem that intravesical BCG elicits strong, local immunity but is usually ineffective at distant sites. This is well illustrated by the absence of sufficient systemic immunity to metastatic disease. Whilst it remains to be decided if HP-NAP will be a TG 003 useful agent in the oncology/urology medical center, it has some interesting characteristics which suggest promise. Amongst these pro-inflammatory and modulatory activities is the.