Arlt Friederike A, Majed Masoud, Wu Jack, Zekeridou Anastasia, Shelly Shahar, Lennon Vanda A, Pittock Sean J, McKeon Andrew, Klein Christopher J, Dubey Divyanshu, Mills John R
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
J Neuroimmunol. 2025 Sep 15;406:578681. doi: 10.1016/j.jneuroim.2025.578681. Epub 2025 Jun 30.
INTRODUCTION/AIMS: Diagnostic evaluation for Lambert-Eaton myasthenic syndrome (LEMS) includes serological testing for voltage-gated calcium channel antibodies (VGCC-P/Q-type [VGCC-PQ] and VGCC-N-type [VGCC-N]). While VGCC-PQ antibodies are well-established biomarkers in LEMS, the clinical utility of VGCC-N antibody testing remains obscure. We aimed to determine the diagnostic value of VGCC-N antibody testing.
A retrospective cross-sectional study was performed. The Mayo Clinic electronic medical record from 1995 to 2021 was reviewed for inclusion of patients fitting clinical electrodiagnostic criteria for LEMS, who were evaluated for serum VGCC antibodies (n = 123). Available sera were additionally tested for SOX1 antibodies (n = 68). Healthy adults were tested for VGCC-PQ and VGCC-N antibodies (n = 122). Clinical performance of each antibody test was evaluated statistically.
Among adult LEMS cases, 84.6 % (n = 99/117) tested positive for VGCC-PQ antibody while none of the healthy controls did. In contrast, 20.5 % (n = 24/117) were VGCC-N antibody positive, of which 95.8 % (n = 23/24) co-occurred with VGCC-PQ antibodies. The frequency of isolated VGCC-N antibody positivity was higher in controls than in LEMS (2.5 % [n = 3/122] vs. 0.9 % [n = 1/117]), and pediatric patients had no VGCC-N antibody reactivity. Neither VGCC-N antibody positivity nor titer was predictive of an associated small-cell lung cancer (SCLC-LEMS). By contrast, SOX1-IgG seropositivity associated significantly with SCLC-LEMS.
Inclusion of VGCC-N antibody testing does not improve diagnostic accuracy for LEMS, nor does it serve as a predictor of LEMS-associated cancers in contrast to SOX1-IgG testing. We recommend the exclusion of VGCC-N antibody testing given its non-specific disease associations and poor positive predictive value in LEMS screening.
引言/目的：兰伯特-伊顿肌无力综合征（LEMS）的诊断评估包括检测电压门控钙通道抗体（VGCC-P/Q型[VGCC-PQ]和VGCC-N型[VGCC-N]）的血清学检测。虽然VGCC-PQ抗体是LEMS中公认的生物标志物，但VGCC-N抗体检测的临床效用仍不明确。我们旨在确定VGCC-N抗体检测的诊断价值。
进行了一项回顾性横断面研究。回顾了梅奥诊所1995年至2021年的电子病历，纳入符合LEMS临床电诊断标准且接受血清VGCC抗体评估的患者（n = 123）。对可用血清额外检测SOX1抗体（n = 68）。对健康成年人检测VGCC-PQ和VGCC-N抗体（n = 122）。对每项抗体检测的临床性能进行统计学评估。
在成年LEMS病例中，84.6%（n = 99/117）的VGCC-PQ抗体检测呈阳性，而健康对照均为阴性。相比之下，20.5%（n = 24/117）的VGCC-N抗体呈阳性，其中95.8%（n = 23/24）与VGCC-PQ抗体同时出现。孤立的VGCC-N抗体阳性频率在对照组高于LEMS组（2.5%[n = 3/122]对0.9%[n = 1/117]），且儿科患者无VGCC-N抗体反应性。VGCC-N抗体阳性及滴度均不能预测相关的小细胞肺癌（SCLC-LEMS）。相比之下，SOX1-IgG血清阳性与SCLC-LEMS显著相关。
与SOX1-IgG检测相比，纳入VGCC-N抗体检测并不能提高LEMS的诊断准确性，也不能作为LEMS相关癌症的预测指标。鉴于其在LEMS筛查中疾病关联不特异且阳性预测价值差，我们建议排除VGCC-N抗体检测。
