Department of Neurosciences, Biomedicine, and Movement Sciences, Neurology Unit, University of Verona, Verona, Italy.
Department of Biomedicine, Metabolic, and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy.
Crit Rev Clin Lab Sci. 2022 Sep;59(6):391-404. doi: 10.1080/10408363.2022.2039591. Epub 2022 Mar 11.
Oligoclonal immunoglobulin G (IgG) bands (OCBs) are a useful diagnostic tool to detect a central humoral response. In particular, cerebrospinal fluid (CSF)-restricted OCBs represent a hallmark of multiple sclerosis (MS), where they can be detected in > 90% of cases and support its diagnosis, although a specific causative agent inducing B cell activation has not yet been identified. The determination of intrathecal IgM, including IgM/lipid-specific IgM OCBs, on the other hand, seems to be of prognostic relevance and is associated with a more aggressive disease course. OCBs can also be present in other central nervous system (CNS) disorders, including antibody-mediated, inflammatory, infectious, and neurodegenerative conditions, as well as in both chronic and early disease stages, suggesting the occurrence of primary or concomitant immune-mediated processes. Finally, intrathecal humoral immune response can also occur, although rarely, in patients with peripheral neuropathies, particularly in those of inflammatory origin, as a possible consequence of blood-spinal nerve root barrier (BSNRB) damage. Isoelectric focusing (IEF) on agarose gels followed by immunoblotting is the technique recommended for OCB detection, analyzing paired undiluted CSF and serum samples. However, technical issues including blot, staining, and IEF reproducibility as well as operator-dependent pattern interpretations decrease reproducibility, causing misinterpretations of results, with significant diagnostic implications. These technical issues can lead to difficulties in distinguishing between negative results (type 1 pattern = absence of OCBs in serum and CSF and type 4 pattern = presence of identical OCBs in both serum and CSF) and results indicating intrathecal IgG synthesis (pattern 2 = presence of OCBs in CSF and type 3 = presence of OCBs in CSF and additional identical OCBs in both serum and CSF). Corrective measures and identification of specialized laboratories with expertise in the field are fundamental to applying this useful technique in clinical practice. In this context, recent research has focused on the automated assessment of CSF kappa free light Ig chains as a more sensitive, non-operator-dependent marker of intrathecal Ig synthesis. We herein review central and peripheral nervous system conditions associated with OCBs and discuss their relation with pathogenetic mechanisms.
寡克隆免疫球蛋白 G（IgG）带（OCB）是一种用于检测中枢体液反应的有用诊断工具。特别是，脑脊液（CSF）受限的 OCB 代表多发性硬化症（MS）的标志，其中超过 90%的病例可以检测到它们，并支持其诊断，尽管尚未确定诱导 B 细胞激活的特定致病因子。另一方面，测定鞘内 IgM，包括 IgM/脂质特异性 IgM OCB，似乎具有预后相关性，并与更具侵袭性的疾病过程相关。OCB 也存在于其他中枢神经系统（CNS）疾病中，包括抗体介导的、炎症性的、感染性的和神经退行性疾病，以及慢性和早期疾病阶段，提示发生原发性或伴随性免疫介导过程。最后，尽管很少见，但在周围神经病患者中，特别是在炎症性起源的患者中，也可能发生鞘内体液免疫反应，这可能是血脊髓神经根屏障（BSNRB）损伤的结果。琼脂糖凝胶等电聚焦（IEF）后免疫印迹是推荐用于 OCB 检测的技术，分析配对的未稀释 CSF 和血清样本。然而，技术问题包括印迹、染色和 IEF 可重复性以及操作员依赖的模式解释降低了可重复性，导致结果的误解，具有重要的诊断意义。这些技术问题可能导致难以区分阴性结果（1 型模式=血清和 CSF 中均不存在 OCB，4 型模式=血清和 CSF 中均存在相同的 OCB）和表明鞘内 IgG 合成的结果（2 型模式=CSF 中存在 OCB，3 型模式=CSF 中存在 OCB，以及血清中存在相同的 OCB）。纠正措施和识别具有该领域专业知识的专门实验室对于将这项有用的技术应用于临床实践至关重要。在这种情况下，最近的研究集中在自动评估 CSF kappa 游离轻链作为一种更敏感、非操作员依赖的鞘内 Ig 合成标志物上。本文综述了与 OCB 相关的中枢和周围神经系统疾病，并讨论了它们与发病机制的关系。
