Intrathecal IgG Synthesis Linked to Disability Worsening in Multiple Sclerosis

By Will Boggs MD

May 02, 2019

NEW YORK (Reuters Health) - Intrathecal IgG synthesis is associated with higher risk of and shorter time to disability worsening in patients with multiple sclerosis (MS), according to findings from the German Competence Network of Multiple Sclerosis.

"I would consider patients with an elevated IgG index at a higher risk to run a more severe disease course," Dr. Bernhard Hemmer of Technical University of Munich told Reuters Health by email. "The marker could be used together with others to guide treatment decisions after MS diagnosis."

Various cerebrospinal fluid (CSF) parameters have been suggested as factors associated with the course of MS, including quantitative measures of intrathecal IgG synthesis.

Dr. Hemmer and colleagues used data from 673 newly diagnosed patients (319 with clinically isolated syndrome, or CIS, and 354 with relapsing-remitting MS, or RRMS) in the German national MS cohort to investigate whether intrathecal IgG synthesis was associated with early disability worsening, as measured by Expanded Disability Status Scale (EDSS) scores.

Intrathecal synthesis of IgG was seen in 352 of 605 patients (58.2%), but only 21.7% had intrathecal synthesis of IgM and 8.8% had intrathecal synthesis of IgA, the researchers report in JAMA Neurology, online April 29.

Four years after study inclusion, 92 of 330 patients (27.9%) with available EDSS scores showed worsening. Regression analysis showed that intrathecal IgG synthesis was associated with a significant doubling of the odds of worsening at that point. There was a similar 2.27-fold increase in the odds of worsening associated with an IgG index >0.70.

Intrathecal IgG synthesis was also associated with shorter time to disability worsening, and there was a nonsignificant association between intrathecal IgG synthesis and risk of relapse.

There was no association between intrathecal IgM or IgA synthesis and the risk or timing of EDSS worsening.

"Perform a spinal tap during the diagnostic work up in MS," Dr. Hemmer said. "CSF findings help to exclude differential diagnoses, increase diagnostic accuracy, and may help allow better prediction of prognosis."

"We need long-term prospective studies to demonstrate that the marker has a predictive value for long-term outcome," he added.

Dr. Jens Kuhle, head of the multiple sclerosis center at the University Hospital Basel, in Switzerland, told Reuters Health by email, "Neurologists have been performing CSF examination mainly to exclude alternative entities in the diagnostic process of most patients with suspected MS without really being aware that a basic CSF parameter could be a valuable biomarker of current and future disease activity."

"If confirmed in independent cohorts that quantitative IgG is a valuable biomarker for early disease worsening, this is a very important finding with potential broad implications since these patients may be chosen for early and highly effective treatment rather than those with less risk of worsening," said Dr. Kuhle, who was not involved in the study. "The results also strengthen the relevance of CSF examination in all patients with suspected MS, not only for diagnostic but also prognostic and patient counseling reasons."


JAMA Neurol 2019.