The human/animal interface: emergence and resurgence of zoonotic infectious diseases.
- Michael Greger
- Critical reviews in microbiology
OBJECTIVES The most frequent sporadic adult motor neuron disease, amyotrophic lateral sclerosis, affects more men, follows no epidemiologic pattern, and was long considered a pure spinal cord disorder. It now becomes evident that the disease is characterized by spinal, cerebral and extra-neuromuscular changes including B-cellular responses and ultrastructural skin alterations. Do these parameters identify subgroups or correlate with the male preponderance of the disease? METHODS We analyzed age at and site of onset, sex, duration of clinical disease, and human foamy retroviral seroreactivity in 47 consecutive patients with a definite diagnosis of amyotrophic lateral sclerosis. The results were compared with antivisna seroreactivity, immunoglobulin isotypes, circulating immune complexes, neopterin and beta 2-microglobulin as well as skin biopsies in respective subsets of the same 47 patients. RESULTS Seroreactivity to recombinant human spuma retrovirus (HSRV) envelope and/or capsid protein was positive in 20/47 amyotrophic lateral sclerosis patients, and 28/30 competed with specific retroviral antibodies on maedi-visna antigen. Anti HSRV-seronegative patients had lower immunoglobulin IgG3 isotype concentrations, while HSRV-gag plus HSRV-env antibody positives demonstrated highest circulating IgG immune complexes. All 11 amyotrophic lateral sclerosis patients partially reacting to recombinant HSRV-env or HSRV-gag antigen were men, and male amyotrophic lateral sclerosis patients tended to have higher total cerebrospinal fluid protein levels. Neopterin and beta 2-microglobulin as markers of a cellular immune activation remained basically normal in serum and cerebrospinal fluid. CONCLUSION We suggest a particular B-lymphocytic and retroviral involvement in this enigmatic, relentlessly progressing, at present untreatable and most frequent neurological system degeneration. To our opinion this situation justifies the search for novel anti-retroviral therapeutic strategies.