Heavy/Light Chain Ratio as a Biomarker for Monitoring Patients with IgM Monoclonal Gammopathy and Anti-MAG Neuropathy

Virginie Planche

doi:10.4172/2329-8790.1000142

Abstract

Background: Patients with neuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies are managed in part by the detection and whenever possible the measurement of IgM-component on serum protein electrophoresis (SPE). Hevylite™ is an immunoassay developed to quantify separately IgMκ and IgMλ and to calculate the IgMκ/IgMλ ratio (HLC ratio). We sought to determine whether HLC ratio can be used to assess diagnosis and to evaluate response to therapy in patients with anti-MAG neuropathy compared to the other currently available tests. Methods: In our tertiary care centre, we retrospectively studied a series of patients with anti-MAG neuropathy. Clinical data and serum samples were collected before treatment and between 6 months and one year maximum after treatment onset. Hevylite™ was performed in a second time after including all patients. Results: Forty-four patients were included (30 with monoclonal gammopathy of undetermined significance (MGUS) and 14 with Waldenstrom’s Macroglobulinemia (WM)). Thirty-nine patients (89%) had a monoclonal IgMκ and 5 patients had a monoclonal IgMλ (11%). Before treatment, all patients had abnormal HLC ratio and displayed a monoclonal IgM detected by SPE, with only 24 (55%) having a quantifiable IgM M-spike. Taking into account the 39 patients with monoclonal IgMκ, HLC ratio was significantly higher for patients with WM versus patients with MGUS (n=39; p=0.03). Before/after treatment comparisons revealed no significant variations of M-spike (p=0.13) and a trend to variations of HLC ratios (p=0.06) according to the clinical response. Conclusions: Our study confirms that HLC ratio using Hevylite TM assay is able to distinguish patients with WM versus patients with MGUS. It further provides numerical evaluation in patients with anti-MAG neuropathy, for who serum M-spike is no measurable or/and anti-MAG antibodies are also upper the quantifiable threshold.

Highlights

Neuropathy associated with monoclonal (M) gammopathy represents 10% of patients with acquired neuropathy [1]
Neuropathy can be seen both in monoclonal gammopathy of undetermined significance (MGUS) or Waldenström’s macroglobulinemia (WM) and the therapy is depending from the lymphoproliferative disease
According to the criteria of the Second International Workshop [10], patients had either polyneuropathy associated with MGUS (n=30) or with WM (n=14)

Summary

Introduction

Neuropathy associated with monoclonal (M) gammopathy represents 10% of patients with acquired neuropathy [1]. More than 50% of these patients have antibodies directed against myelin-associated glycoprotein (anti-MAG antibodies) [2,3]. Anti-MAG neuropathy associated with IgM monoclonal gammopathy constitutes a distinctive clinical syndrome characterized by male predominance, late age of onset, slow progression and predominantly sensory symptoms [3,4]. Many assays can be used to monitor patients with neuropathy associated with anti-MAG antibodies, each one has limitations. Patients with neuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies are managed in part by the detection and whenever possible the measurement of IgM-component on serum protein electrophoresis (SPE). We sought to determine whether HLC ratio can be used to assess diagnosis and to evaluate response to therapy in patients with anti-MAG neuropathy compared to the other currently available tests

Objectives

Methods

Results

Discussion

Conclusion