Identification of α-tubulin as an autoantigen recognized by sera from patients with neuropsychiatric systemic lupus erythematosus

In a previous study we found in 50% of patients with neuropsychiatric manifestations of systemic lupus erythematosus (NP-SLE) organ specific antibodies to 45–56 kD proteins in a 100,000 g supernatant (SN) from bovine brain mitochondria. Aim of the present study was to identify the corresponding target antigen.A 100,000 g SN from bovine brain mitochondria was applied to SDS-gel electrophoresis. A 50 kD band recognized by sera from patients with NP-SLE in the Western blot (WB) was excised from the gels and applied to mass spectrometry. The identified protein was expressed in Escherichia coli and retested against sera from eleven patients with NP-SLE (severe symptoms n = 6, mild symptoms n = 5), 26 SLE-patients without NP manifestations and 53 controls (patients with multiple sclerosis, epilepsy, healthy blood donors).Mass spectrometry of the 50 kD band revealed the presence of α-tubulin. Applying the recombinant α-tubulin in the WB, four of the eleven NP-SLE patients (36%), one of the 26 patients with SLE without NP manifestations (4%) and none of the 53 controls reacted with α-tubulin. The antibodies were more frequently found in patients with severe (50%) than with mild NP-SLE (20%).α-tubulin may be a novel marker autoantigen for a neuropsychiatric manifestation at least in a subgroup of patients with SLE. Whether anti-α-tubulin antibodies are of pathogenetic relevance has still to be clarified.

Research highlights► A 50 kD protein of CNS tissue is recognized by sera from patients with NPSLE. ► The corresponding antigen has been identified by mass spectrometry as α-tubulin. ► Anti-α-tubulin antibodies occur in about 40% of NPSLE patients. ► Anti-α-tubulin antibodies are specific markers for NPSLE. ► Their functional activity has still to be evaluated.