{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T23:03:08Z","timestamp":1780527788408,"version":"3.54.1"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2002,7,11]],"date-time":"2002-07-11T00:00:00Z","timestamp":1026345600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2002,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To examine whether autoantibodies recognizing granzyme B (GB)\u2010cleaved autoantigens are associated with ischemic digital loss (IDL) in limited systemic sclerosis (SSc).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifteen of 19 patients with limited SSc and IDL were matched by age, sex, race, and duration of disease to controls with limited SSc but without IDL. The sera were used to immunoblot HeLa cell lysates and chromosome preparations that had been incubated in vitro in the absence or presence of GB. Anticentromere antibodies (ACAs) were assayed by immunofluorescence and immunoprecipitation of in vitro\u2010translated centromere proteins (CENP\u2010B and CENP\u2010C). Immunoprecipitation of GB\u2010cleaved CENPs was also performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GB\u2010cleaved autoantigens were immunoblotted by 16 of 19 IDL sera (84.2%) compared with 6 of 15 non\u2010IDL sera (40.0%) (odds ratio 8.0, 95% confidence interval 1.6\u201340.0). This association persisted after adjustment for ACA status. Furthermore, the presence of antibodies to centromere proteins as well as to GB\u2010cleaved antigens was highly specific for IDL, occurring in 12 of 19 IDL patients (63.2%) and in none of 15 controls (<jats:italic>P<\/jats:italic> &lt; 0.0001). An identical 60\u2010kd GB\u2010generated fragment was recognized by 5 of 16 IDL sera (31.3%) and was demonstrated to arise through GB\u2010mediated cleavage of CENP\u2010C. GB\u2010cleaved CENP\u2010C fragments were recognized preferentially over the intact CENP\u2010C molecule by antibodies from patients with IDL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The striking recognition of GB\u2010generated autoantigen fragments by sera from patients with limited SSc and IDL constitutes the first in vivo evidence that antibodies against GB\u2010generated centromeric peptide fragments identify a distinct clinical subset.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.10407","type":"journal-article","created":{"date-parts":[[2002,9,11]],"date-time":"2002-09-11T02:05:28Z","timestamp":1031709928000},"page":"1873-1884","source":"Crossref","is-referenced-by-count":65,"title":["Recognition of Granzyme B\u2010generated autoantigen fragments in scleroderma patients with ischemic digital loss"],"prefix":"10.1002","volume":"46","author":[{"given":"Lionel","family":"Schachna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrick M.","family":"Wigley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan C.","family":"Gelber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Casciola\u2010Rosen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,7,11]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-73-2-317"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00990.x"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.42.1.23"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310207"},{"key":"e_1_2_5_6_2","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S0889-857X(21)00738-9","article-title":"Autoantibodies in scleroderma","volume":"18","author":"Rothfield NF","year":"1992","journal-title":"Rheum Dis Clin North Am"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400460"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar75"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80550-6"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.6.815"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.3.1433"},{"key":"e_1_2_5_12_2","doi-asserted-by":"crossref","first-page":"14703","DOI":"10.1016\/S0021-9258(18)98743-0","article-title":"Granzyme A binding to target cell proteins. 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