Hepatitis C virus (HCV) represents the major risk factor for mixed cryoglobulinemia (MC), a small‐vessel vasculitis that may evolve into an overt B‐cell non‐Hodgkin's lymphoma. Here, we aimed to identify a biomarker signature for the early diagnosis of minimal residual disease (MRD). We assessed free light chains (FLCs), IgM k,and IgM λ heavy/light chain (HLC) pairs, and vascular endothelial growth factor (VEGF) in sera from 34 patients with MC vasculitis (32 HCV‐ and 2 HBV‐related), treated with low‐dose rituximab (RTX). FLCs and IgM HLCs were measured by turbidimetric assay; VEGF by an enzyme‐linked immunosorbent assay. After RTX, the positive (complete + partial) clinical and laboratory responses were of 85.29% and 50%, respectively; in contrast, the mean levels of FLCs, IgM HLCs, and VEGF were substantially unaffected in most patients and still above the normal range. In those achieving a reduction of FLCs and IgM k and λ chains values within the range of normality, we found that post‐treatment free λ chains and IgM k values correlated with clinical and laboratory response. Our results suggest that high levels of FLCs, IgM HLCs, and VEGF could represent the signature of “dormant” B cell clones’ activity that could be very useful to identify MRD indicative of possible relapse or worsening outcome.

中文翻译：

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利妥昔单抗治疗的混合性冷球蛋白血症患者的最小残留疾病的生物标志物

丙型肝炎病毒（HCV）是混合性冷球蛋白血症（MC）的主要危险因素，这是一种小血管血管炎，可能演变为明显的B细胞非霍奇金淋巴瘤。在这里，我们旨在为早期诊断最小残留疾病（MRD）识别生物标志物特征。我们评估了34例MC血管炎（32例HCV和2例HBV相关）患者血清中的游离轻链（FLC），IgM k和IgMλ重/轻链（HLC）对以及血管内皮生长因子（VEGF） ，用小剂量利妥昔单抗（RTX）治疗。FLC和IgM HLC通过比浊法进行测定；通过酶联免疫吸附试验测定VEGF。RTX治疗后，临床（实验室）的阳性（完全+部分）和实验室应答分别为85.29％和50％。相比之下，FLC，IgM HLC，VEGF和VEGF在大多数患者中基本不受影响，仍高于正常范围。在正常范围内实现FLCs和IgM k和λ链值降低的研究中，我们发现治疗后的游离λ链和IgM k值与临床和实验室反应相关。我们的结果表明，高水平的FLC，IgM HLC和VEGF可能代表“休眠” B细胞克隆的活性特征，这对于识别可能复发或恶化的MRD可能非常有用。