Neutralization by human serum samples of a transmissible agent isolated from the cerebrospinal fluid of neurological patients

New Microbiol. 2011 Oct;34(4):345-50. Epub 2011 Oct 31.

Abstract

A transmissible cytotoxic agent thought to be associated with one or more misfolded protein(s) was found in several cerebrospinal fluid (CSF) samples from neurological patients. Since some experiments carried out to identify this unusual infectious factor showed the block of its propagation by rabbit gammaglobulins (IgGs), the search for such an activity by human IgGs was programmed. Neutralizing assays carried out using human sera as IgGs source showed a blocking property displayed by: twenty serum samples from as many patients with a diagnosis of acute infection, two of ten sera from healthy subjects and four serum samples from patients with lupus erythematous (SLE). When neutralizing sera were tested on cell cultures in immunofluorescence assays for the serum ability to label specific protein( s), similar fluorescent pictures resulted in treated and control cells. On the other hand, the SLE serum samples disclosed a granulosity of the nuclear material of cytotoxic cells in accordance with the DNA apoptotic laddering reported in previous papers. Oxidative disorders, as suggested by the immunoblotting analysis of the antioxidant enzymes Mn-superoxide dismutase (SOD2) and heme-oxygenase 1 (HO-1), point to an alteration of the oxidative pathway among the causes of the DNA damage induced by the cytotoxic transmissible agent under study.

MeSH terms

  • Animals
  • Brain Ischemia / blood
  • Brain Ischemia / cerebrospinal fluid*
  • Brain Ischemia / immunology*
  • Cells, Cultured
  • Cerebrospinal Fluid Proteins / blood
  • Cerebrospinal Fluid Proteins / cerebrospinal fluid
  • Cerebrospinal Fluid Proteins / immunology*
  • Cytotoxins / blood
  • Cytotoxins / cerebrospinal fluid
  • Cytotoxins / immunology
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • Heme Oxygenase-1 / blood
  • Heme Oxygenase-1 / cerebrospinal fluid
  • Humans
  • Immunoglobulin G / pharmacology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / cerebrospinal fluid
  • Lupus Erythematosus, Systemic / immunology
  • Neuroglia / cytology
  • Neuroglia / immunology
  • Neutralization Tests / methods*
  • Oxidative Stress / physiology
  • Proteostasis Deficiencies / blood
  • Proteostasis Deficiencies / cerebrospinal fluid*
  • Proteostasis Deficiencies / immunology*
  • Rabbits
  • Superoxide Dismutase / blood
  • Superoxide Dismutase / cerebrospinal fluid

Substances

  • Cerebrospinal Fluid Proteins
  • Cytotoxins
  • Immunoglobulin G
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Superoxide Dismutase
  • superoxide dismutase 2