A Proliferation‐inducing Ligand (APRIL) is Expressed by Astrocytes and is Increased in Multiple Sclerosis

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Abstract
A proliferation-inducing ligand (APRIL) is a newly described member of the tumour necrosis factor (TNF) superfamily that was first identified as a factor favouring tumorigenesis. APRIL is also important for several immune functions, including B-cell survival. Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS) that is commonly diagnosed in early adulthood. Several TNF superfamily members have been identified in brains of patients with MS, although their exact function within the CNS is presently unknown. To investigate whether APRIL is expressed in the CNS, we studied APRIL protein expression by immunohistochemistry in MS patients and controls. Morphologically, APRIL-positive cells appeared to be astrocytes. A two-colour immunohistochemistry revealed that APRIL expression was cytoplasmic, granular and restricted to GFAP-positive cells. Conversely, HLA class II-positive microglial cells were negative for APRIL expression. APRIL-positive cells were fewer in brains of controls compared with those with MS. We further corroborated our findings by studying APRIL protein expression in several glioblastoma cell lines, and found APRIL to be expressed by most cell lines analysed. APRIL's binding partner syndecan-1 (CD138) was detected in brains of neither MS nor control patients. Furthermore, B cells were detectable in the brain of one of five patients with MS. We conclude that APRIL is expressed by reactive astrocytes in MS and may be of relevance in gliotic scar formation.