Response to letter from Dr Hongliang Zhang entitled ‘B-cell activating factor in the cerebrospinal fluid of neuromyelitis optica and multiple sclerosis’

We thank the authors of this letter for their comments ¹ on our work. ² We definitely agree that the sample size is limited and further verification of our findings is needed to confirm the diagnostic and prognostic role of B-cell activating factor (BAFF) as a biomarker in neuromyelitis optica (NMO) and multiple sclerosis (MS).

We also agree that the increase in BAFF may not only explain the exacerbations induced by interferon treatment, but also support the important role of B cells in the pathogenesis of NMO. However, since astrocytes produce substantial quantities of BAFF, our findings may equally indicate the importance of astrocytes pathology in NMO. We postulate that an activation phase, induced by anti-aquaporin-4 antibodies, may precede astrocyte damage.

We agree that there might be a selection bias (i.e. the interferon and glatiramer acetate [GA]-treated groups included patients with more severe disease which had required immunomodulatory therapy) and this possibility has to be further investigated by a longitudinal study. However, our small experience with few selected cases (mentioned in the manuscript) has indicated that the introduction of interferon treatment caused an increase in the levels of BAFF, as compared with the pre-treatment values, in these patients. This finding has been previously reported also by Krumbholz et al. ³ In our study, there was absolutely no correlation between the severity of the disease and the levels of BAFF, which can advocate against the possibility of a selection bias, related to the severity of the disease.

The finding of increased BAFF levels only in the cerebrospinal fluid (CSF) and not in the blood could be explained by the fact that the blood and CSF samples were not taken from the same patients at the same time points. It is therefore still possible that the increased levels of BAFF in the CSF are caused by its transfer from the serum through the blood–CSF barrier (B-CSF-B) and related to the integrity of the B-CSF-B. Alternatively, as mentioned above, the increased CSF BAFF could be the result of a local production of BAFF by astrocytes or by activated B cells that had migrated through the blood–brain barrier (BBB) into the CSF. Recently, Daridon et al. ⁴ reported that B cells from patients with Sjögren’s syndrome express BAFF. This could be the case also with B cells from NMO patients, providing an additional clue for the pivotal role of B cells in NMO pathogenesis.