Antibodies against microglia/brain macrophages in the cerebrospinal fluid of a patient with acute amyotrophic lateral sclerosis and presenile dementia.
This is the report of a case of a 41-year-old male patient with a rapidly progressing amyotrophic lateral sclerosis (ALS) combined with a severe presenile dementia. Screening for antibody binding on fresh-frozen human brain sections, we found that the patient's cerebrospinal fluid contained antibodies against microglia, the dominant and potentially cytotoxic immuneffector cell of the brain. This finding extends previous observations of CSF autoantibodies against microglia in neurodegenerative diseases. It demonstrates that in addition to antigens of neuronal origin (e.g. anti-Purkinje cell antibodies in paraneoplastic cerebellar dysfunction), glial antigens also appear to be under the surveillance of the CNS and/or the peripheral immune system. Our data provide evidence for a close link between neurodegeneration and the activation of microglia; a possible local antigen production against microglia/brain macrophages, which might regulate the concomitant glial activation in neurodegenerative diseases; and the presence of microglia-binding cerebrospinal antibodies as a marker for the acuity of the disease process underlying the acute deterioration of the neurological and cognitive performance in patients with, e.g., ALS. Future therapeutic strategies could therefore include the modulation of the possibly disease-promoting activation of microglia/brain macrophages.
Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried near Munich, FRG.
R B
RB
Banati
J
J
Gehrmann
M
M
Kellner
F
F
Holsboer
D000208:Acute Disease; D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid / Q000276:immunology*; D001323:Autoantibodies / Q000134:cerebrospinal fluid*; D001921:Brain / Q000166:cytology / Q000276:immunology*; D003704:Dementia / Q000134:cerebrospinal fluid / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D008297:Male; D017628:Microglia / Q000276:immunology*
D001323:Autoantibodies