Understanding the antibody repertoire in Neuropsychiatric Systemic Lupus Erythematosus and Neuromyelitis Optica Spectrum Disorders: do they share common targets?

Objective DWEYS-IgG cross-reactive with DNA and the N-methyl-D-aspartate receptor subunits GluN2A/GluN2B has been associated with neuropsychiatric systemic lupus erythematosus (NPSLE). DWEYS-IgG has not been investigated in demyelinating NPSLE (dNPSLE) or in another demyelinating disorder, Neuromyelitis Optica Spectrum Disorder (NMOSD), which is also a disease of young women and associated with aquaporin-4 (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibodies. We investigated the frequency of these brain-reactive antibodies in NPSLE, dNPSLE and NMOSD. Methods Serum from NPSLE (n=108), SLE (n=38), NMOSD (n=33) and healthy controls (HC; n=106) was measured for brain-IgG and AQP4, MOG, GluN2A/GluN2B and double-stranded-DNA (dsDNA) antibodies. Results AQP4-IgG was positive in 27/33 (82%) NMOSD, 3/11 (27%) dNPSLE, and was negative in NPSLE without demyelination (NPSLEwd), SLE and HC. MOG-IgG was detected at high-titers in 50% (3/6) AQP4-IgG negative NMOSD and at low-titers in 18% (2/11) dNPSLE and 1% (1/97) NPSLEwd. dsDNA-IgG was present in 33% (11/33) NMOSD. Only 12% (4/33) NMOSD were DWEYS-IgG positive, compared to 29% (11/38) SLE and 55% (59/108) NPSLE. DWEYS-IgG was present in 58% (56/97) NPSLEwd and 27% (3/11) dNPSLE. A similar frequency of brain-IgG was detected in NPSLEwd (75%; 72/96), dNPSLE (82%; 9/11) and SLE (84%; 32/38); and was less frequent in NMOSD (61%; 20/33). Conclusion Patients with demyelinating disease should be tested for AQP4-IgG, MOG-IgG and DWEYS-IgG. AQP4–IgG is diagnostic for NMOSD; none of the antibodies is diagnostic for dNPSLE. dsDNA-IgG are present in NMOSD but are not cross-reactive with DWEYS, indicating a different antigenic stimulus and potentially different mechanisms of tissue damage. This article is protected by copyright. All rights reserved.