Late-breaking: Role for CSF markers in autoimmune astrocytopathies

Recent results of an international study confirm that concentrations of the glial fibrillary acidic protein (GFAP) are elevated in neuromyelitis optica spectrum disorder (NMOSD) and adds a novel astrocytic biomarker, glutamine synthetase (GS), to the laboratory test panel.

NMOSD is a group of immune-mediated central nervous system disorders, including optic neuritis, acute myelitis (LETM), and area postrema syndrome (see Figure). The pathogenesis of NMOSD is better understood since the identification of pathogenic aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibodies. However, despite a compatible clinical phenotype some patients remain seronegative.

Figure. Autoantibodies broadened the clinical spectrum, which facilitates diagnosis and guides treatment decisions [1]



AQP4, aquaporin; LETM, acute myelitis; MOG, myelin oligodendrocyte glycoprotein; NMOSD, neuromyelitis optica spectrum disorder; ON, optic neuritis

In an international study, Dr Iris Kleerekooper (University College London, United Kingdom) and colleagues investigated astrocytopathy across NMOSD using 2 biomarkers: the astrocytic enzyme GS, and the structural astrocytic protein GFAP. The aim was to explore levels of astrocytic injury across NMOSD in patients with NMOSD (n=43), MS (n=69), optic neuritis (n=5), and non-neurological control subjects (n=37).

In patients with NMOSD, both median GFAP and GS levels were significantly elevated compared with controls (P=0.021 and P<0.001, respectively). Only GFAP levels significantly distinguished NMOSD from MS (P=0.037) and only GS levels distinguished controls from MS (P=0.001). GFAP and GS levels correlated significantly (P<0.001) and did not differ significantly between AQP4-Ab-seropositive and -seronegative NMOSD, although GFAP levels of AQP4-Ab-seronegative NMOSD patients were markedly increased.

This study confirmed that GFAP concentrations are elevated in NMOSD. GS is a novel astrocytic biomarker, although it is less specific than GFAP. The increased GFAP levels in seronegative NMOSD patients suggests that the spectrum of autoimmune astrocytopathies may be wider than only AQP4-Ab-seropositive cases, and there could be merit in hunting for novel autoimmune targets in these patients. As additional astrocytic autoimmune target(s) potentially exist in double-antibody-seronegative NMOSD, identification of these targets would facilitate diagnosis and clinical decision making.

1. Misu T, Fujihara K. Clin Exp Neuroimmunol. 2019;10:9-17.
2. Kleerekooper I, et al. ECTRIMS 2019, abstract 340.

Posted on 8 November, 201927 March, 2024