Local synthesis of IgA in the cerebrospinal fluid of patients with neurological diseases

Abstract

To date qualitative studies of IgA in the cerebrospinal fluid in neurological disease, particularly multiple sclerosis, have been few and given mixed results. The aim of this study was to identify local synthesis of IgA by detection of clonal IgA bands, in a large cohort of patients with a variety of neurological disorders, using polyacrylamide gel electrophoresis, transfer of protein to nitrocellulose membranes and specific staining. Of 2,097 sequentially analysed patients with suspected neurological disease 54 (2.6%) had locally synthesised IgA; most notably, IgA was present in 39 of 291 (13%) patients with suspected multiple sclerosis. The latter group also had a significant excess of light-chain production, particularly free kappa, when compared to multiple sclerosis patients without local synthesis of IgA. Locally synthesised IgA was also demonstrated in inflammatory, infectious and autoimmune diseases of the central nervous system. This qualitative technique is simple and suitable for routine analysis of cerebrospinal fluid, and further qualitative studies of IgA may be useful in investigating the pathophysiology of certain neurological disorders.

Human immunoglobulin A (IgA)‐specific ligands from combinatorial engineering of protein A

“…IgA is predominantly localized to mucosal surfaces but is also present at high levels in plasma [11] and believed to play an important role in defence mechanisms against infections [12]. IgA is also implicated in several diseases including IgA nephropathy [13], coeliac disease [14], Henoch‐Schönlein purpura [15] and neurological diseases [16], where IgA levels are monitored as a disease marker or investigated for a more direct involvement in disease progression. Interestingly, recent data suggest that IgA should be an interesting isotype to validate for development of antibodies for immunotherapy applications, including cancer therapy, due to its effective recruitment of neutrophils [17].…”

Opsoclonus—myoclonus—dysequilibrium syndrome: cytological and immunological dynamics in the serial cerebrospinal fluid in two patients

“…IgA may be involved in the response to viruses. Intrathecal IgA synthesis has been demonstrated in a number of viral CNS infections [22]. A clear elevation of IgA index was transient at the time of the most severe clinical disability in the second patient which may reflect temporary inflammation within the CNS.…”

The Intrathecal Humoral Immune Response: Laboratory Analysis and Clinical Relevance

“…The preferential synthesis of dimeric IgA within the CNS (13) can be used as a marker of an intrathecal synthesis in detecting these dimers by polyacrylamide gel electrophoresis (14).…”