Serum and cerebrospinal kappa free light chains in psychiatric syndromes with neuronal and paraneoplastic autoantibodies.

Background: Kappa free light chains (KFLC) are a surrogate parameter for intrathecal immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA) synthesis confirming neuroinflammation in the central nervous system (CNS). It is unclear whether KFLC can differentiate primary psychiatric disorders from neural autoantibody-associated psychiatric syndromes.

Methods: We enrolled 76 patients with psychiatric diagnoses ICD-10 (International Classification of Diseases, 10th revision) (F00-09, F10-19, F20-F20-29, F30-39, F40-49) and cerebrospinal fluid (CSF) as well as blood samples from our biobank. Commercial assays were used to determine neural autoantibodies. KFLC in serum, and CSF samples were assessed by nephelometry (Siemens Atellica NEPH 630 analyzer). We calculated the relative intrathecal fraction (IF%) of KFLC and index as a KFLC quotient and albumin quotient. Criteria for autoimmune encephalitis and autoimmune-mediated psychiatric syndromes were evaluated in patients to determine an autoimmune basis for the psychiatric symptoms.

Results: Neither the number of patients with elevated KFLC, a KFLC index nor the KFLC IF percentage served as an instrument for differentiating between autoantibody-positive (n=18) and autoantibody-negative (n=58) psychiatric patients. Patients with elevated KFLC levels in CSF had a higher proportion of lymphocytes than patients with non-elevated KFLC as a non-significant trend. We observed a non-significant trend towards higher CSF/serum IgM, but no trend for CSF/serum IgA or CSF/serum IgG ratio in patients with elevated KFLC levels than in those with non-elevated KFLC. No probable autoantibody-positive or seronegative autoimmune encephalitis was detected in patients. However, we observed an autoantibody-associated psychiatric syndrome in 6 out of 10 patients with elevated KFLC-IF, and the detection of elevated KFLC improved the diagnosis of probable autoimmune disease in 4 out of 10 patients (40%).

Conclusions: Elevated KFLC levels may indicate psychiatric patients presenting any intrathecal immunoglobulin synthesis and thus help to evaluate an autoimmune basis in psychiatric syndromes. Furthermore, it should be added as a novel criterion for intrathecal immunoglobulin synthesis in autoimmune-related psychiatric syndromes. Further large-scale research is needed to elucidate the role of KFLC in autoimmune-mediated psychiatric disorders and to verify the observed trends in CSF parameters in patients with elevated KFLC.