The presence of renal autoantibodies in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic neurological disorder characterised by demyelinating inflammatory lesions within the central nervous system, which are separated in both time and space. Although the cause of MS is unknown it is generally agreed that the disease is a result of an autoimmune response against components of the central nervous system (CNS) that occurs through complex interactions between genetic and environmental factors. There is growing evidence that autoreactive antibodies may play a role in the progression of the disease analogous to the role that has been established for aquaporin-­‐4 antibodies in the pathogenic process of the demyelinating disease, neuromyelitis optica (NMO). In the process of screening the sera of neurological patients for NMO antibodies, a preliminary study found that a novel renal antibody may be present in patients with MS. This renal antibody bound to elements in the proximal brush border and was referred to as ABBA (anti-­‐brush border antibody). The current study aimed to: determine the prevalence of ABBA in MS, determine whether there is a correlation with ABBA and any brain antibodies and determine the target to which ABBA binds. Indirect immunofluorescence on rat renal and neural tissue was used to determine the prevalence of renal antibodies while human renal cell lines were used to determine the antigenic target to which these antibodies bind. This study is the first to investigate the presence of ABBA and other renal antibodies in MS patients and the first to identify high titre antibodies in the disease. While the presence of ABBA was not found to be significantly different between MS cases and control groups, ABBA was found to be more prevalent in inflammatory neurological conditions and a correlation was found between ABBA and axonal-­‐nodal antibodies in inflammatory conditions. The current study was unable to identify the target to which ABBA binds. The presence of high titre antiglomerular antibodies (AGLA), anti-­‐distal tubule (ADA) and anti-­‐cortical collecting duct antibodies (ACCA) in the serum of patients with MS was an unexpected and novel finding and has not previously been documented. Neuroinflammatory cases had a higher prevalence of AGLA, which were also associated with the presence of both anti-­‐axonal nodal antibodies and anti-­‐ perivascular antibodies. In the absence of renal pathology or documented nephrotoxic medications as well as not identifying the antigenic target, the significance of this observation remains unclear. However, possible explanations are discussed.