Jornal de Hematologia e Doenças Tromboembólicas
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Heavy/Light Chain Ratio as a Biomarker for Monitoring Patients with IgM Monoclonal Gammopathy and Anti-MAG Neuropathy

Virginie Planche, Laurent Arnaud, Karine Viala, Marie Anne Hospital, Makoto Miyara, Jean Marc Leger, Jean Neil, Véronique Leblond and Lucile Musset

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 Waldenström’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.