Detection of oligoclonal IgA in cerebrospinal fluid samples by an isoelectric focusing procedure

Abstract

An isoelectric focusing procedure for the detection of oligoclonal IgA in cerebrospinal fluid (CSF) samples is presented. CSF IgA bands were found in 69% of patients with various inflammatory neurological diseases, in 22% of patients with other neurological diseases, but in none of the patients with non-neurological diseases. In patients with inflammatory neurological diseases we examined the relationship between an intrathecal synthesis of oligoclonal IgA and an intrathecal IgA synthesis as proved by a formula recently described by Reiber and Felgenhauer: 83% of patients with an intrathecal IgA synthesis according to the formula of Reiber and Felgenhauer also showed CSF IgA bands whereas 59% of patients without an intrathecal IgA synthesis displayed an intrathecal synthesis of oligoclonal IgA. Seventeen percent of patients with inflammatory neurological diseases were characterized by an intrathecal synthesis of oligoclonal IgA but did not show either an intrathecal IgA synthesis or an intrathecal synthesis of oligoclonal IgG, the detection of oligoclonal IgA therefore being the only evidence of an intrathecal humoral immune response in these patients.

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

“…In one study the amount of IgA in the CSF in multiple sclerosis patients was reported to be too low to allow investigation of oligoclonal IgA, but weak IgA bands were demonstrated in two patients with central nervous system (CNS) infections (neuroborreliosis and neurosyphilis) [9]. Withold et al [35] demonstrated oligoclonal IgA in CSF in 20 of 29 patients with inflammatory neurological disease (including only one multiple sclerosis patient) and 4 of 18 patients with other neurological diseases. Sindic et al [29] demonstrated CSF-restricted oligoclonal IgA in five of 115 neurological patients, including 2 of 33 patients with multiple sclerosis [29].…”

“…The results of early studies were inconclusive, with oligoclonal IgA in CSF being reported in a single patient in one study [10] and absent in other studies [2,15] of multiple sclerosis. More recent studies, all using isoelectric focusing (IEF), have clearly demonstrated oligoclonal IgA in various neurological disorders [9, 29,35]. However, the numbers of patients studied to date, particularly with multiple sclerosis, have been relatively small.…”

Quantitation of intrathecal immunoglobulin synthesis – a new empirical formula

“…Although some efforts have been undertaken to detect oligoclonal IgA and IgM by IEF, these methods are still controversially debated , and in contrast to IgG OCBs there is no generally accepted method available which might serve as a gold standard. Some studies on these isotypes have been performed with no clear association between specific OCBs and quantitative measurements . In a clinical context IgA predominance could be found in rare cases such as neurotuberculosis and brain abscess.…”

“…Accordingly, the German Society for Cerebrospinal Fluid Diagnostics and Neurochemistry recommends considering intrathecal IgA or IgM syntheses of less than 10% as non‐pathological . Furthermore, two studies found a discrepancy between calculated Ig synthesis and specific oligoclonal bands detected by IEF for IgA and IgM , although detection of intrathecal IgA and IgM by IEF is under debate.…”

The cerebrospinal fluid in multiple sclerosis. Quantitative assessment of intrathecal immunoglobulin synthesis by empirical formulae

“…Reiber has reported hyperbolic Qalb dependent reference limits for QIgA and QleM (Reiber, 1994) and Ohman et al, (1993) have developed extended IgA-and IgM-indices. It has been suggested that isoelectnc focusing is also superior to the Reiber formulae in detecting intrathecal synthesis of IgA and IgM (Sharief el al., 1990; Kaiser and Lucking, 1993;Withold et al, 1994). It is, however, not known to what extent low level intrathecal IgA and IgM synthesis in diseases not traditionally believed to be associated with immunoglobulin synthesis may affect the reference limits employed for these formulae.…”