Low reliability of anti-KIR4.183-120 peptide auto-antibodies in multiple sclerosis patients

Abstract

Background: Multiple sclerosis (MS) is an autoimmune disease for which auto-antibodies fully validated as diagnostic and prognostic biomarkers are widely desired. Recently, an immunoreactivity against the inward rectifying potassium channel 4.1 (KIR4.1) has been reported in a large proportion of a group of MS patients, with amino acids 83-120 being the major epitope. Moreover, a strong correlation between anti-KIR4.1_83-120 and anti-full-length-protein auto-antibodies titer was reported. However, this finding received limited confirmation.

Objective: Validation of the diagnostic potential of anti-KIR4.1_83-120 antibodies in 78 MS patients, 64 healthy blood donors, and 42 individuals with other neurological diseases.

Methods: Analysis of anti-KIR4.1_83-120 antibodies by enzyme-linked immunosorbent assay (ELISA) using a mouse antiserum we produced as a new ELISA reliability control. Additionally, evaluation of reactivity against 293-T cells transiently transfected with full-length KIR4.1 by flow cytometry.

Results: We found antibodies to KIR4.1_83-120 only in 13 out of 78 (16.6%) MS patients; among these, only 2 were positive for anti-full-length KIR4.1 antibodies.

Conclusion: Employing a new reliability control and a new cytofluorometric assay, we cannot support anti-KIR4.1_83-120 auto-antibodies as a reliable biomarker in MS.

Keywords: KIR4.1; auto-antibodies; biomarker; enzyme-linked immunosorbent assay; flow cytometry; multiple sclerosis.