Relevance of Kappa and Lambda Free Light Chains in Autoimmune Astrocytopathy Associated With Anti-GFAP Antibodies

Abstract

Introduction: The kappa-free light chain (κ-FLC) index is known to be highly sensitive and specific for diagnosing multiple sclerosis (MS), while little is understood about lambda (λ)-FLC. This study assessed the κ-FLC and λ-FLC indices in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy.

Methods: This multicenter study compares κ-FLC and λ-FLC indexes among patients with autoimmune GFAP astrocytopathy and sex- and age-matched MS (positive control group) as well as symptomatic controls (headaches and small cerebral vessel disease, as the negative control group). We describe the correlation of both indexes with clinical variables and outcomes in the GFAP astrocytopathy cohort.

Results: A total of 93 patients were included (31 in each group). The median κ-FLC index was higher in the MS group (65.5 [35.7; 118.3]) compared to the GFAP astrocytopathy group (26.1 [11.4; 78.4], p = 0.062). With a κ-FLC index threshold of 6.1, the proportion of patients with a positive κ-FLC index was similar between the MS (94%) and GFAP-astrocytopathy groups (84%, p = 0.425). The median λ-FLC index was higher in the GFAP astrocytopathy group (45.5 [28.4; 96.9]) than in the MS group (10.6 [2.2; 29.1], p < 0.001). In the GFAP-astrocytopathy group, both CSF λ-FLC and the λ-FLC index at baseline were correlated with the last follow-up mRS (⍴ = 0.46, r² = 0.088, p = 0.014, and ⍴ = 0.32, r² = 0.12, p = 0.101, respectively).

Conclusion: The κ-FLC index alone cannot distinguish between autoimmune GFAP astrocytopathy and MS. We indicate a potential diagnostic and prognostic role of the λ-FLC index in GFAP astrocytopathy that needs confirmation in independent cohorts.

Keywords: autoimmune GFAP‐astrocytopathy; biomarkers; cerebrospinal fluid; kappa‐free light chains; lambda‐free light chains.

FIGURE 1

κ‐FLC and λ‐FLC associations with OCB. In all cohorts, the median κ‐FLC index (Figure 1A) and λ‐FLC index (Figure 1B) were significantly higher in OCB‐positive patients compared to OCB‐negative patients (p < 0.001 for both comparisons). ***Represents p value < 0.001. ** Represents p value <0.01. CSF, cerebrospinal fluid; FLC, free light chains; OCB, oligoclonal bands.

FIGURE 2

κ‐FLC and λ‐FLC biomarkers across groups. **Represents p value < 0.01. ***Represents p value < 0.001. CSF, cerebrospinal fluid; FLC, free light chains; GFAP, glial fibrillary acidic protein; MS, multiple sclerosis.

FIGURE 3

Association between last follow‐up clinical outcome and CSF λ‐FLC and λ‐FLC index in the GFAP‐astrocytopathy group. A low correlation was observed between CSF λ‐FLC (A) and λ‐FLC index (B) and the last follow‐up visit mRS score (p = 0.014 and p = 0.101, respectively). mRS, modified Rankin scale.