Background: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. Objective: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE. Methods: The study included a predominantly population-based cohort with clinical and serological investigations of 208 patients with SLE, followed prospectively since 1995. All patients received immunosuppressive treatment. NMOSD was evaluated retrospectively based on the 2015 International Panel for NMOSD Diagnosis (IPND) criteria. Polymorphisms in programmed cell death protein 1 (PDCD-1) PD-1.3 G/A were genotyped. AGP4-IgG and other autoantibodies, including myelin oligodendrocyte glycoprotein (MOG), was determined blinded to clinical diagnosis. Results: Of 208 patients with SLE, 45(22%) had neuropsychiatric (NP) SLE, and CNS involvement predominated in 30 of 45 (67%) patients. Serum AQP4-IgG was detected in 2 of 30 (6.7%) neuropsychiatric SLE (NPSLE) patients both of whom had myelitis and antiphospholipid syndrome; one patient also had myasthenia gravis. None had MOG-IgG. PD-1.3A allele was not associated with SLE nor with NPSLE. Conclusion: AQP4-IgG autoimmune syndrome may rarely co-exist with SLE, and such patients have other NMOSD-typical syndromes such as myelitis.
Myelitis in neuromyelitis optica spectrum disorder: The long and the short of it
Objective A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)‐IgG as biomarker was recently characterized. Here, 102 patients with GFAP‐IgG positivity are described. Methods The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell‐based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell‐based (n = 323) assays. Results Median symptom onset age was 44 years (range = 8–103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP‐IgG positivity was encountered in serum controls by tissue‐based assay (0.5%) or cell‐based assay (1.5%), and in CSF controls by cell‐based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N‐methyl‐D‐aspartate receptor–IgG and aquaporin‐4–IgG coexisted (71%). Six patients with prolonged follow‐up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency. Interpretation GFAPα‐IgG, when detected in CSF, is highly specific for an immunotherapy‐responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298–309
Neuromyelitis optica spectrum disorder diagnostic criteria: Sensitivity and specificity are both important