In previous work a
polyclonal B cell activator has been detected in the serum of patients with
rheumatoid arthritis (RA). This activator is associated with
alpha 2-macroglobulin (alpha 2M) and its activity is blocked by low-Mr
trypsin inhibitors, which suggests that it may be a
protease-alpha 2M complex. Here we determined the possibility of developing a routine clinical chemistry test for detection of this complex in patients' blood. We measured with
chromogenic substrates the total proteolytic activity of citrated plasma and of the alpha 2M immunoabsorbed from plasma. Low-Mr substrates containing Arg were degraded much better by plasma from RA patients than by plasma from patients with other
arthritides. Low-Mr substrates containing
Leu, Lys, or Gly or the large-Mr substrate
Azocoll were not degraded by RA patients' plasma. alpha 2M from RA patients' plasma attached to a solid-phase immunoabsorbent degraded an Arg-containing tripeptide much better than did the alpha 2M from normal donors, from patients with
systemic lupus erythematosus, or from those with joint
inflammation of other, "non-autoimmune" origin. Although the
enzyme associated with alpha 2M in the plasma from RA patients appeared to be similar to
trypsin, the differences in optimal pH,
cation concentration, degradation of Lys-containing substrates, and
biological activity suggest otherwise. We speculate that the alpha 2M-protease complexes are generated in the immune system and contribute to the inflammatory and autoimmune phenomena in RA.