The Role of Assay of Free Immunoglobulin Light Chains in the Diagnosis of the Onset of Multiple Sclerosis
Objective. To assess the diagnostic value of assaying immunoglobulin (IgG) light chains at the onset of multiple sclerosis (MS). Materials and methods. A total of 226 patients took part in the study; group 1 (n = 111) were patients with clinically isolated syndrome (CIS) with development to MS within the first two years; group 2 (n = 49) were patients with CIS who did not progress to MS in the first two years; group 3 (n = 20) consisted of patients with inflammatory diseases of the central nervous system. The reference group (group 4, n = 46) consisted of patients with noninflammatory CNS diseases. The following immunological indicators were assessed in the patients: the clonal nature of cerebrospinal fluid (CSF) IgG and the concentrations of free ϰ and λ light chains in the CSF and their ratio. Results. Synthesis of free light chains was significantly greater in group 1 than groups 2 and 4. Free light chain synthesis in group 3 was significantly greater than that in groups 2 and 4 but was not significantly different from that in group 1. Free light chain production was significantly greater in patients with oligoclonal IgG synthesis than in patients without oligoclonal synthesis. The level of production of free light chains in patients of group 1 was significantly greater than that in group 2, regardless of whether or not oligoclonal IgG was produced. The most valuable diagnostic markers were the concentration and the coefficient of CSF:serum concentrations of κ light chains. Use of these parameters along with assessment of the clonality of IgG synthesis produced a 50% reduction in number of false negative results. Independently of other factors, increases in κ chain levels led to a 9.718-fold increase in the probability of a diagnosis of MS. Conclusions. Assay of free light chains as a lab marker increases the accuracy of diagnoses of MS and provides an indirect evaluation of the risk that CIS will progress to complete MS in the next two years.
Keywordsmultiple sclerosis clinically isolated syndrome free light chains oligoclonal bands biomarkers
Unable to display preview. Download preview PDF.
- 1.A. N. Boiko, O. O. Favorova, O. G. Kulakova, and E. I. Gusev, “Epidemiology and etiology of multiple sclerosis,” in: Multiple Sclerosis, I. A. Gusev, I. A. Zavalishin, and A. N. Boiko (eds.), Moscow (2004).Google Scholar
- 6.S. V. Lapin and E. P. Evdoshenko, “Laboratory methods for the diagnosis of multiple sclerosis and other neurological diseases,” Sprav. Zaved. KDL, No. 1, 22 (2011).Google Scholar
- 7.G. S. Makshakov, S. V. Lapin, and E. P. Evdoshenko, “Current concepts of the intrathecal humoral immune response and the diagnostic significance of detecting oligoclonal immunoglobulins in multiple sclerosis,” Zh. Nevrol. Psikhiat., 116, No. 2–2, 14–20 (2016), doi: https://doi.org/10.17116/jnevro20161162214-20.CrossRefGoogle Scholar
- 9.R. Dobson, S. Ramagopalan, A. Davis, and G. Giovannoni, “Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude,” J Neurol. Neurosurg. Psychiatry, 84, 909–914 (2013), doi: https://doi.org/10.1136/jnnp-2012-304695.CrossRefPubMedGoogle Scholar
- 13.N. A. Totolyan, A. A. Gotovchikov, S. V. Lapin, et al., “Intrathecal synthesis of immunoglobulins in the diagnosis and differential diagnosis of multiple sclerosis,” Zh. Nevrol. Psikhiat., 112, No. 9, Iss. 2, 73–86 (2012).Google Scholar
- 15.Andersson, J. Alvarez-Cermeno, G. Bernardi, et al., “Cerebrospinal fluid in the diagnosis of multiple sclerosis. A consensus report,” J. Neurol. Neurosurg. Psychiatr., 57, 897–902 (1994).Google Scholar