THU0329 Autoantibodies to GABAB Receptors Detected in Patients with Systemic Lupus Erythematosus
Authors: H. Tsuchiya, S. Haga, Y. Takahashi, Y. Ishizaka, A. Mimori
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The gamma-aminobutyric acid receptor type B (GABAR<sub>B</sub>) is a G-protein-coupled receptor involved in signal transduction by GABA, an inhibitory neurotransmitter. GABAR<sub>B</sub> comprises two subunits: GABAR<sub>B1</sub> and GABAR<sub>B2</sub>. Interestingly, these subunits were identified as target antigens in stiff person syndrome and limbic encephalitis<sup>1-3)</sup>. To identify novel candidate antigens in patients with systemic lupus erythematosus (SLE), we explored a random peptide display library using serum samples of these patients and identified GABAR<sub>B</sub> subunits as candidate novel autoantigens in SLE. <h3>Objectives</h3> To prove the clinical significance of autoantibodies to GABAR<sub>B</sub> subunits (α-GABAR<sub>Bs</sub>), we first examined the frequency of α-GABAR<sub>Bs</sub> in patients with connective tissue diseases. In addition, we focused on the presence of α-GABAR<sub>Bs</sub> in patients with SLE and investigated the possible link of α-GABAR<sub>Bs</sub> with disease activity and neuropsychiatric symptoms. <h3>Methods</h3> An enzyme-linked immunosorbent assay (ELISA) was performed with recombinant Flag-tagged proteins of GABAR<sub>B1</sub> (1–475 amino acids (aa)) and GABAR<sub>B2</sub> (1–480 aa), corresponding to ectodomains of GABAR<sub>B1b</sub> and GABAR<sub>B2</sub>, respectively. Titers of α-GABAR<sub>Bs</sub> were obtained by determining the absorbance (Ab) at OD450, which was obtained after reacting with a horseradish peroxidase conjugated second antibody to human IgG. ELISA was first performed on sera from healthy subjects (n = 15) and patients with SLE (n = 88), scleroderma (n = 20), myositis (n = 20), and vasculitis (n = 20). Next, 23 cerebrospinal fluid (CSF) samples from patients with SLE were analyzed in the same manner. The clinical significance of the obtained results was then evaluated on the basis of clinical data of the enrolled patients. <h3>Results</h3> The titers of α-GABAR<sub>B1</sub> and α-GABAR<sub>B2</sub> in patients with acute-phase SLE were significantly high compared with those in healthy subjects (<i>P</i> &lt; 0.001, Ab-OD450 = 0.51 vs. 0.09 for α-GABAR<sub>B1</sub> and 0.48 vs. 0.06 for α-GABAR<sub>B2</sub>, respectively). Notably, more than 80% patients with acute-phase SLE demonstrated higher titers than the maximum value detected in healthy subjects. Moreover, the titers of α-GABAR<sub>Bs</sub> in patients with acute-phase SLE (n = 50) were significantly higher than those in patients with chronic-phase SLE (n = 38) (<i>P</i> &lt; 0.001), which significantly decreased after treatment (n = 8). Strong correlations were observed between titers of α-GABAR<sub>B1</sub> and α-GABAR<sub>B2</sub> (r<sub>s</sub> = 0.87, <i>P</i> &lt; 0.0001), both of which correlated with the titer of α-dsDNA (<i>P</i> &lt; 0.0001, r<sub>s</sub> = 0.47 for α-GABAR<sub>B1</sub> and r<sub>s</sub> = 0.59 for α-GABAR<sub>B2</sub>). Although we did not observe a positive correlation of serum α-GABAR<sub>Bs</sub> with neuropsychiatric symptoms, we found that α-GABAR<sub>B1</sub> and α-GABAR<sub>B2</sub> were detected in seven of the 16 CSF samples obtained from patients with neuropsychiatric SLE (43.8%). In contrast, no significant high titers of α-GABAR<sub>Bs</sub> were detected in serum samples of patients with scleroderma, myositis, and vasculitis. <h3>Conclusions</h3> Serum α-GABAR<sub>Bs</sub> could be novel markers for patients with active-phase SLE. To correlate α-GABAR<sub>Bs</sub> with neuropsychiatric SLE, further investigation would be required to confirm the presence of α-GABAR<sub>Bs</sub> in CSF of these patients. <h3>References</h3> Curr Opin Neurol. 2012 Dec;25(6):795-801. Lancet Neurol. 2011 Aug;10(8):759-72. Neurology. 2011 Mar 1;76(9):795-800. <h3>Disclosure of Interest</h3> None Declared