Correlation of a bioassay with the clinical status of patients with rheumatoid arthritis.

Joint synovia and fluids taken from patients with various stages of rheumatoid arthritis (RA) were injected into embryonated chicken eggs, resulting in characteristic joint abnormalities ("crooked toes") in the extremities of the embryos and chicks. There was a direct correlation between the number of the induced lesions and the stages of the human RA disease. The percentage of abnormality of the bioassays was consistent with acute, subacute, chronic or remission phases in the clinical course of the RA disease. Specimens from chronic or remission RA joints produced few or no experimental abnormalities, suggesting few or no infectiojs RA particles available to the bioassay. Likewise, dilution of acute RA joint fluids of 1 : 100 by 0.15M NaCl resulted in a characteristic extinction of the bioassay test, suggesting that specimens could lose their reactivity in the bioassay because of too great dilution in the preparation of homogenates of the synovia. Numerical changes in the bioassay consistently followed the changes in the clinical courses of the RA during waning and waxing episodes. A useful numerical scale (0--100%) of the 10-day embryonated egg bioassay as an indication or measurement of the severity of the RA in the patient is proposed on the basis of these observations.

Further studies on the specific infectious agent isolated in rheumatoid arthritis.

The active agent in crude or extracted materials from patients with acute rheumatoid arthritis (RA), when injected into embryonated eggs, produced an increased percentage of characteristic "crooked toe" defects in the bioassay. Experimental RA chick materials also produced these defects. A protein-free ribonucleic acid extract from RA synovia and joint fluids of patients with acute or subacute classical RA produced the same experimental RA lesions as did the crude materials, but non-RA materials and controls did not. The injected RA material produced the "crooked toe" disease in chicks in direct proportion to the clinically diagnosed severity of the RA in the patient, and inversely with dilution.