High κ free light chain is a potential biomarker for double seronegative and ocular myasthenia gravis

Abstract

ObjectiveTo investigate the hypothesis that free light chain (FLC) sera levels could serve as a biomarker for myasthenia gravis (MG), especially for the subgroups of seronegative MG and ocular MG.MethodsSera from 73 patients with MG (20 seronegative for antiacetylcholine receptor [AChR] and anti–muscle-specific kinase and 53 positive for anti-AChR, which were clinically divided into 24 patients with ocular type, 45 with generalized type, and 4 with unequivocal clinical manifestation) and 49 healthy controls were studied for κ FLC and λ FLC levels with the Freelite human FLC kits.ResultsThe κ but not the λ levels of FLC were significantly increased in the patients with MG, including those with double seronegative MG and ocular MG, compared with the healthy controls. The specificity for double seronegative MG and ocular MG were both 98.0% when κ FLC was ≥25.0 mg/L. Increased κ FLC levels were not affected by the patient's sex, age at MG onset, the presence of thymic pathology, or different treatments.ConclusionsElevated serum κ FLC may serve as a biomarker for MG in suspected patients who are double seronegative and in those with only ocular manifestations when serology is inconclusive.Classification of evidenceThis study provides Class III evidence that high κ FLC levels distinguished patients with MG, including those who were double seronegative, from healthy controls.

Systemic Inflammatory Response Index, a Potential Inflammatory Biomarker in Disease Severity of Myasthenia Gravis: A Pilot Retrospective Study

“…Notably, a growing body of evidence suggests significant variations within lymphocyte subpopulations in MG patients. 27–29 Besides, elevated free light chains (FLC), a biomarker of B cell activation, have been detected in MG patients and hold promise as diagnostic indicators, 30 , 31 suggesting the important role of lymphocytes in morbidity of MG. SIRI, by integrating three key inflammatory blood cell counts, provides a more comprehensive and sensitive reflection of the inflammatory state within the human body. The combined elevation of monocytes and neutrophils alongside the reduction in lymphocytes strengthens SIRI’s ability to monitor and potentially predict the inflammatory status in MG patients.…”

Laboratory Investigation of Hybrid IgG4 k/λ in MuSK Positive Myasthenia Gravis

“…In this context, we recently reported the first evidence that MG pts display increased circulating level of free immunoglobulin light chains (FLC), describing different profiles in AChR-and MuSK-MG [22]. Considered as an emerging direct biomarker of B cell activity in AD, FLC has been confirmed as a challenging biomarker for MG in suspected pts who are double seronegative [23]. Since the demonstration that hybrid IgG4 mediates pathogenesis in MuSK-MG [11][12][13], our interest was focused on understanding the clinical relevance of such molecules.…”

Overview of biomarkers in myasthenia gravis

“…Recently, an interesting study showed that κ FLC, but not λ FLC, increases in the SNMG and OMG. The authors concluded the κ/λ ratio could be used as a novel biomarker for MG patients who do not have another condition associated with FLC alternation [62].…”