The Coexistence of Antibodies to Neuronal Cell and Synaptic Receptor Proteins, Gangliosides and Selected Neurotropic Pathogens in Neurologic Disorders in Children

Abstract

Various primarily non-autoimmune neurological disorders occur synchronously with autoantibodies against tissues in the nervous system. We aimed to assess serum and cerebrospinal fluid (CSF) autoantibodies in children with neurologic disorders. To find new diagnostic tools, we compared the laboratory and clinical findings between the distinguished groups. Retrospectively, 508 patients were divided into six subgroups: neuroinfections, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, neurologic autoimmune and demyelinating diseases, epilepsy, pervasive developmental disorders and other patients. We analysed serum anti-aquaporin-4, antiganglioside, neuronal antinuclear and cytoplasmic antibodies, as well as antibodies against surface neuronal and synaptic antigens in the CSF and serum. We involved available demographic and clinical data. Autoantibodies appeared in 165 (32.3%) children, with 24 showing multiple types of them. The most common were anti-neuroendothelium (anti-NET), anti-N-Methyl-D-Aspartate receptor (anti-NMDAr), anti-glial fibrillary acidic protein and anti-myelin antibodies bothering 46/463 (9.9%), 32/343 (9.4%), 27/463 (5.8%) and 27/463 (5.8%), respectively. Anti-NET and anti-NMDAr antibodies appeared more frequently in children with autoimmunity (p = 0.017; p < 0.001, respectively), increasing the autoimmune disease risk (OR = 2.18, 95% CI 1.13-13.97; OR = 3.91, 95% CI 1.86-8.22, respectively). Similar pathomechanisms appeared in diseases of different aetiology with clinical spectrums mimicking each other, so we proposed the model helping to diagnose autoimmune disease. We proved the influence of age, living place and medical history on the final diagnosis.

Keywords: N-methyl-D-aspartate receptor; autoimmune diseases; child development disorders; infectious diseases; polyneuropathies.

Figure 1

The distribution of ASO titre (A), CSF cytosis (B), CSF protein concentration (C), IgG index (D) and age (E). Abbreviations: ASO—antistreptolysin O, CNS—central nervous system, CSF—cerebrospinal fluid, IQR—interquartile range, PANDAS—pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, PDD—pervasive developmental disorder.

Figure 2

The logistic regression models. (A) The three-factor model characteristics (PCC = 70.71%; SP = 84.66%; SE = 40.79%). (B) The two-factor model characteristics (PCC = 71.97%; SP = 86.73%; SE = 34.09%). (C) The models’ comparison. Abbreviations: CMV—cytomegalovirus, NET—neuroendothelium, NMDAr—N-methyl-D-aspartate receptor, PCC—a percentage of consonants correct; SE—sensitivity; SP—specificity.