{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:21:04Z","timestamp":1773800464328,"version":"3.50.1"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2012,4,1]],"date-time":"2012-04-01T00:00:00Z","timestamp":1333238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Collagenase\n            <jats:named-content content-type=\"genus-species\">Clostridium histolyticum<\/jats:named-content>\n            (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\n            <jats:named-content content-type=\"genus-species\">Clostridium histolyticum<\/jats:named-content>\n            , 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 \u00b1 10 years old [mean \u00b1 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.\n          <\/jats:p>","DOI":"10.1128\/cvi.00018-12","type":"journal-article","created":{"date-parts":[[2012,2,23]],"date-time":"2012-02-23T01:51:51Z","timestamp":1329961911000},"page":"562-569","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Assessment of Potential Cross-Reactivity of Human Endogenous Matrix Metalloproteinases with Collagenase Clostridium histolyticum Antibodies in Human Sera Obtained from Patients with Dupuytren's Contracture"],"prefix":"10.1128","volume":"19","author":[{"given":"Thomas J.","family":"Edkins","sequence":"first","affiliation":[{"name":"Edkins Pharma Services, LLC, Wayne, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roland","family":"Koller-Eichhorn","sequence":"additional","affiliation":[{"name":"Koller &amp; Koller LLC, Zurich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack A.","family":"Alhadeff","sequence":"additional","affiliation":[{"name":"Protein Therapeutics Consulting, Center Valley, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Mayer","sequence":"additional","affiliation":[{"name":"Celerion Switzerland AG, Fehraltorf, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinrich","family":"Faust","sequence":"additional","affiliation":[{"name":"Celerion Switzerland AG, Fehraltorf, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin J.","family":"Del Tito","sequence":"additional","affiliation":[{"name":"Auxilium Pharmaceuticals, Inc., Malvern, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600310"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2008.01082.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi901656f"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409230701340019"},{"key":"e_1_3_2_6_2","volume-title":"Assay development for investigating cross-reactivity of MMP proteins with anti-AUX-I and anti-AUX-II antibodies in clinical samples, report DAA90736\/90737","author":"Celerion","year":"2010","unstructured":"Celerion. 2010. Assay development for investigating cross-reactivity of MMP proteins with anti-AUX-I and anti-AUX-II antibodies in clinical samples, report DAA90736\/90737. Celerion, Fehraltorf, Switzerland."},{"key":"e_1_3_2_7_2","volume-title":"Immunogenicity of biopharmaceuticals","author":"Chamberlain P","year":"2008","unstructured":"ChamberlainP. 2008. Presenting an immunogenicity risk assessment to regulatory agencies, vol VIII, p 239\u2013258. In van de WeertMM\u00f8llerEH (ed), Immunogenicity of biopharmaceuticals. Springer, New York, NY."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.sap.0000205819.53215.52"},{"key":"e_1_3_2_9_2","volume-title":"Document reference EMEA\/CHMP\/BMWP\/14327\/2006","author":"European Medicines Agency","year":"2007","unstructured":"European Medicines Agency. 2007. Guideline on immunogenicity assessment of biotechnology-derived therapeutic proteins. Document reference EMEA\/CHMP\/BMWP\/14327\/2006. European Medicines Agency, London, England."},{"key":"e_1_3_2_10_2","unstructured":"European Medicines Agency. 2011. Xiapex: EPAR summary for the public. European Medicines Agency London England. http:\/\/www.ema.europa.eu\/ema\/index.jsp?curl=pages\/medicines\/human\/medicines\/002048\/human_med_001423.jsp&mid=WC0b01ac058001d124. Accessed 7 March 2012."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0266-7681(03)00013-5"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810866"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/cen-v087n029.p020"},{"key":"e_1_3_2_14_2","volume-title":"AAPS Biotechnol. Conf., San Francisco, CA","author":"Kirschner S","year":"2010","unstructured":"KirschnerS. 2010. A regulatory perspective on immunogenicity surveillance considerations in the post-approval phase of biotherapeutics. AAPS Biotechnol. Conf., San Francisco, CA. American Association of Pharmaceutical Scientists, Arlington, VA."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar2315"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-0101(01)00163-5"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.06.002"},{"key":"e_1_3_2_18_2","first-page":"116","article-title":"Clostridium histolyticum collagenases: a new look at some old enzymes","volume":"1","author":"Mookhtiar KM","year":"1992","unstructured":"MookhtiarKMVan WartHE. 1992. Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix Suppl. 1:116\u2013126.","journal-title":"Matrix Suppl."},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0266-7681(84)80019-4"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2008.09.020"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0749-0712(21)00900-8"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0363-5023(96)80368-6"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2005.238"},{"key":"e_1_3_2_24_2","unstructured":"U.S. Food and Drug Administration. 2011. Drugs @ FDA: FDA approved drug products. U.S. Food and Drug Administration Rockville MD. http:\/\/www.accessdata.fda.gov\/scripts\/cder\/drugsatfda\/index.cfm?fuseaction=Search.DrugDetails. Accessed 9 October 2011."},{"key":"e_1_3_2_25_2","volume-title":"Assay development for immunogenicity testing of therapeutic proteins","author":"U.S. Food and Drug Administration","year":"2009","unstructured":"U.S. Food and Drug Administration. 2009. Draft guidance for industry. Assay development for immunogenicity testing of therapeutic proteins. U.S. Department of Health and Human Services, Food and Drug Administration, Rockville, MD."}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00018-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00018-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:46:48Z","timestamp":1627591608000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00018-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1128\/CVI.00018-12"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00018-12","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4]]},"assertion":[{"value":"2012-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-02-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-03-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}