BAFF serum levels in myasthenia gravis: effects of therapy.

B lymphocyte activating factor (BAFF) belonging to the tumour necrosis factor (TNF) ligand super-family is a key survival factor for B lymphocytes [1]. In transgenic mice, BAFF overproduction is associated with lymphocytic disorders and autoimmunity [2], and increased serum BAFF levels are found in human autoimmune diseases [3]. Myasthenia gravis (MG) is an antibody-mediated disease of neuromuscular transmission. Most patients have serum antibodies against the acetylcholine receptor (AChR). Anti-AChR positive MG is associated with thymus alterations, such as follicular hyperplasia and thymoma [4]. Thymus hyperplasia is characterized by expanded thymus perivascular spaces with infiltration of T and B lymphocytes and germinal centre formation; BAFF was found to be expressed in the MG hyperplastic thymus where it could foster a microenvironment permissive to B-cells [5]. Our aim was to evaluate serum BAFF levels in MG patients in different phases of their disease and the effects of therapy. We tested serum samples from 66 patients, 52 women and 14 men (M/W: 1/3.7) aged 14–74 years (mean 39) and 41 healthy controls, 32 women and 9 men (M/W: 1/3.5), aged 20–66 years (mean 41). Patient population included: 61 anti-AChR positive (42 early-onset, 11 lateonset and 8 thymoma) and 5 early-onset anti-AChR negative MG cases. No patient had anti-muscle specific kinase (MuSK) antibodies. All patients but two had generalized disease. Thymectomy was performed on all thymoma cases and 42/47 early-onset MG patients; a typical thymus hyperplasia was found in 35/42 of these cases. BAFF levels were measured in 52 patients before immunosuppressive (IS) treatment; in 13 of these cases, who had undergone thymectomy with histological findings of thymus hyperplasia, we evaluated serial samples taken before and 5–33 years after thymectomy; 14 patients were under IS therapy (mostly with prednisone) at the inclusion. BAFF levels were measured in duplicate by quantitative sandwich enzyme immunoassay using commercial Quantikine kit (R&D Systems, USA). The normal range for the BAFF assay was defined by the geometric mean BAFF level ?2 SD in controls. Statistical analysis was performed by paired and unpaired Student t test and ANOVA. All patients and controls gave informed consent to the study. Mean serum BAFF levels were significantly higher in the MG population (938.8 ± 284 pg/mL) than in controls (797 ± 192 pg/mL) (p = 0.005). Overall, 20/66 patients (30.3%) had BAFF levels above the normal range. BAFF values did not correlate with disease severity. In 33 MG samples taken before any treatment the mean BAFF value was 953 ± 268 pg/mL, and it did not differ in 19 samples from patients who had undergone thymectomy and had never received IS therapy (1,060 ± 266 pg/mL) (p = 0.14). In the 13 patients in whom serial samples (before and after thymectomy) were tested, serum BAFF levels did not significantly change after thymectomy (p = 0.22) (Fig. 1) with no clearly correlation with clinical outcome. On the other hand, in MG patients under IS therapy, BAFF This study has been approved by the local ethics committee and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.