Collagenase Clostridium histolyticum (CCH) contains a fixed ratio of class I (AUX-I) and class II (AUX-II)
collagenases and is used as treatment for
Dupuytren's contracture. These two Zn-dependent
enzymes, produced by the Gram-positive bacterium Clostridium histolyticum, are related functionally to
matrix metalloproteinases (
MMPs) which, among other functions, degrade the extracellular matrix. Since AUX-I and AUX-II exhibit sequence similarities to human
MMPs, we assessed MMP-1 (
interstitial collagenase), MMP-2 (
gelatinase A), MMP-3 (
stromelysin 1), MMP-8 (
collagenase 2), and MMP-13 (
collagenase 3) for cross-reactivity with anti-AUX-I and anti-AUX-II
antibodies in patient serum. Serum samples from 71 subjects enrolled in a long-term clinical study (58 males and 13 females; 63 ± 10 years old [mean ± standard error]) were evaluated for cross-reactivity with the five
MMPs using the two validated
enzyme-linked
immunosorbent assays (ELISAs). Inhibition cutoff points for anti-AUX-I and anti-AUX-II
antibodies were based on assay inhibition obtained with a nonspecific
protein, bovine
gamma globulin, which was tested for each clinical sample. No
MMP cross-reactivity was found for any of the 71 clinical antibody-positive sera evaluated. Sequence identity assessments indicated minimal, nonmeaningful alignments of the
MMPs and AUX-I/AUX-II. Furthermore, clinical adverse event assessments indicated no safety signals related to
MMP inhibition. The bioanalytical results, sequence identity, and clinical assessments consistently did not demonstrate cross-reactivity between CCH antidrug
antibodies and endogenous human
matrix metalloproteinases. The results presented here suggest that treatment of
Dupuytren's contracture patients with CCH does not lead to any clinical adverse events associated with
MMP inhibition.