The Impact of Immunomodulatory Treatment on Kappa Free Light Chains as Biomarker in Neuroinflammation

Abstract

Background: Kappa free light chains (KFLC) are a promising new biomarker to detect neuroinflammation. Still, the impact of pre-analytical effects on KFLC concentrations was not investigated.

Methods: KFLC concentrations were measured in serum and cerebrospinal fluid (CSF) of patients with a newly diagnosed multiple sclerosis (MS) or clinically isolated syndrome (CIS) before (n = 42) or after therapy with high-dose methylprednisolone (n = 65). In prospective experiments, KFLC concentrations were analyzed in the same patients in serum before and after treatment with high-dose methylprednisolone (n = 16), plasma exchange (n = 12), immunoadsorption (n = 10), or intravenous immunoglobulins (n = 10). In addition, the influence of storage time, sample method, and contamination of CSF with blood were investigated.

Results: Patients diagnosed with MS/CIS and treated with methylprednisolone showed significantly lower KFLC concentrations in serum as untreated patients. Repeated longitudinal investigations revealed that serum KFLC concentrations continuously decreased after each application of methylprednisolone. In contrast, other immune therapies and further pre-analytical conditions did not influence KFLC concentrations.

Conclusion: Our results show prominent effects of steroids on KFLC concentrations. In contrast, various other pre-analytical conditions did not influence KFLC concentrations, indicating the stability of this biomarker.

Keywords: Kappa free light chains; biomarker; cerebrospinal fluid; intrathecal synthesis; multiple sclerosis; pre-analytic impact factors; serum.

Figure 1

Serum concentrations after methylprednisolone. Serum concentrations of patients diagnosed with multiple sclerosis according to the McDonald criteria of 2017 and clinically isolated syndrome who converted to multiple sclerosis during follow-up. Each dot represents a single measurement of a patient who was untreated or received intravenous methylprednisolone with the indicated dose. Depicted are serum concentrations of kappa free light chains (KFLC) (A), immunoglobulin type G (IgG) (B), IgA (C), and IgM (D) in untreated patients (n = 42) and patients who received methylprednisolone infusion of 1000 mg (n = 8), 2000 mg (n = 25), 3000 mg (n = 16), 4000 mg (n = 9), or 5000 mg (n = 7). p-values of significant differences are illustrated as asterisks.

Figure 2

Cerebrospinal fluid (CSF) concentrations after methylprednisolone. CSF concentrations of patients diagnosed with multiple sclerosis according to the McDonald criteria of 2017 and clinically isolated syndrome who converted to multiple sclerosis during follow-up. Each dot represents a single measurement of a patient who was untreated or received intravenous methylprednisolone with the indicated dose. Depicted are CSF concentrations of kappa free light chains (KFLC) (A), immunoglobulin type G (IgG) (B), IgA (C), and IgM (D) in untreated patients (n = 42) and patients who received methylprednisolone infusion of 1000 mg (n = 8), 2000 mg (n = 25), 3000 mg (n = 16), 4000 mg (n = 9), or 5000 mg (n = 7). p-values of significant differences are illustrated as asterisks.

Figure 3

Serum concentrations after methylprednisolone in prospective patients. Serum concentrations of patients whose data and samples were collected in 2018 and 2019 are shown. Depicted are serum concentrations of kappa free light chains (KFLC) (A1), immunoglobulin type G (IgG) (B1), IgA (C1), and IgM (D1). The percentage decrease of concentrations of KFLC (A2), IgG (B2), IgA (C2), and IgM (D2) in serum is also shown. Patients treated with intravenous methylprednisolone for 3 days are depicted as blue dots and columns (n = 7), while patients with a treatment of 5 days are depicted as red dots and columns (n = 9). Blood samples were taken before and after 24, 48, and 96 h of treatment with 1000 mg of intravenous methylprednisolone per day. p-values of significant differences are illustrated as asterisks.

Figure 4

Serum concentrations after plasma exchange in prospective patients. Serum concentrations of patients whose data and samples were collected in 2018 and 2019 are shown. Depicted are serum concentrations of kappa free light chains (KFLC) (A), immunoglobulin type G (IgG) (B), IgA (C), and IgM (D). Patients treated with 3 cycles of plasma exchange therapy are depicted as blue dots (n = 5), while patients with 5 cycles of treatment are depicted as red dots (n = 7). Blood samples were taken before and after 24, 48, 72, 96, and 120 h of treatment with one cycle of plasma exchange per day. p-values of significant differences are illustrated as asterisks.

Figure 5

Serum concentrations after immunoadsorption in prospective patients. Serum concentrations of patients whose data and samples were collected in 2018 and 2019 are shown. Depicted are serum concentrations of kappa free light chains (KFLC) (A), immunoglobulin type G (IgG) (B), IgA (C), and IgM (D). Blood samples were taken before and after 24, 48, 72, 96, and 120 h of treatment with one cycle of immunoadsorption per day (n = 10). p-values of significant differences are illustrated as asterisks.

Figure 6

Serum concentrations after intravenous immunoglobulin (IVIG) in prospective patients. Serum concentrations of patients whose data and samples were collected in 2018 and 2019 are shown. Depicted are serum concentrations of kappa free light chains (KFLC) (A), immunoglobulin type G (IgG) (B), IgA (C), and IgM (D). Blood samples were taken before and after treatment with intravenous immunoglobulin in a dosage between 30 g and 40 g per day, resulting in a total dosage of 60 g–160 g (n = 10). p-values of significant differences are illustrated as asterisks.