{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T22:49:28Z","timestamp":1761518968074},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[1995,4,1]],"date-time":"1995-04-01T00:00:00Z","timestamp":796694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,28]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n               <jats:p>Since they were first described, serum IgG antibodies to the stratum corneum of rat oesophagus epithelium, highly specific for rheumatoid arthritis (RA), have been consensually called anti-keratin antibodies (AKA). However, we recently demonstrated that they actually recognize three new proteins of rat oesophagus epithelium distinct from cytokeratins, and also human epidermal filaggrin. In this work we provided further evidence that AKA and RA-associated anti-filaggrin autoantibodies are the same antibodies. Moreover, analysing by indirect immunofluorescence on human skin a large series of 212 well characterized RA sera and anti-filaggrin autoantibodies purified from RA sera by affinity chromatography. we demonstrated the specific binding of AKA to the stratum corneum of human epidermis and the absence of any staining of the granular keratinocytes. This binding was confirmed and the AKA antigen precisely localized in human epidermis by immunoelectron microscopy. The antigen was found to be restricted to the filaggrin-containing intracellular fibrous matrix of the corneocytes, up to the desquamating cells. In contrast, MoAbs directed to human filaggrin and to profilaggrin, its precursor, not only stained the intracellular matrix of the tower corneocytes but also the keratohyatin granules of the granular cells, where profilaggrin is stored. These results reinforced by the absence of immunoblotting reactivity of RA sera to profilaggrin suggest that the epitopes recognized by AKA are absent from profilaggrin. Their identification may provide more insight into the pathogenesis of RA.<\/jats:p>","DOI":"10.1111\/j.1365-2249.1995.tb03608.x","type":"journal-article","created":{"date-parts":[[2010,7,26]],"date-time":"2010-07-26T17:25:10Z","timestamp":1280165110000},"page":"90-98","source":"Crossref","is-referenced-by-count":13,"title":["The rheumatoid arthritis-associated autoantibodies to filaggrin label the fibrous matrix of the cornified cells but not the profilaggrin-containing keratohyalin granules in human epidermis"],"prefix":"10.1093","volume":"100","author":[{"given":"M","family":"SIMON","sequence":"first","affiliation":[{"name":"Department of Biology and Pathology of the Cell, Toulouse-Purpan School of Medicine, University of Toulouse III, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"VINCENT","sequence":"additional","affiliation":[{"name":"Department of Biology and Pathology of the Cell, Toulouse-Purpan School of Medicine, University of Toulouse III, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"HAFTEK","sequence":"additional","affiliation":[{"name":"INSERM U346\/CNRS (Dr D. Schmitt), E. Herriot Hospital, Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E","family":"GIRBAL","sequence":"additional","affiliation":[{"name":"Department of Biology and Pathology of the Cell, Toulouse-Purpan School of Medicine, University of Toulouse III, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"SEBBAG","sequence":"additional","affiliation":[{"name":"Department of Biology and Pathology of the Cell, Toulouse-Purpan School of Medicine, University of Toulouse III, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V","family":"GOM\u00c8S-DAUDRIX","sequence":"additional","affiliation":[{"name":"Department of Biology and Pathology of the Cell, Toulouse-Purpan School of Medicine, University of Toulouse III, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G","family":"SERRE","sequence":"additional","affiliation":[{"name":"Department of Biology and Pathology of the Cell, Toulouse-Purpan School of Medicine, University of Toulouse III, Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2008,6,28]]},"reference":[{"key":"2022011517444137900_b1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1136\/bmj.2.6182.97","article-title":"Anti-keratin antibodies in rheumatoid arthritis","volume":"2","author":"Young","year":"1979","journal-title":"Br Med J"},{"key":"2022011517444137900_b2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1136\/ard.40.3.267","article-title":"Significance of laminar antikeratin antibodies to rat oesophagus in rheumatoid arthritis","volume":"40","author":"Scott","year":"1981","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1136\/ard.40.3.263","article-title":"Antiperinuclear factor and keratin antibodies in rheumatoid arthritis","volume":"40","author":"Johnson","year":"1981","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b4","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/BF02042772","article-title":"Clinical relevance of antikeratin antibodies in rheumatoid arthritis","volume":"1","author":"Miossec","year":"1982","journal-title":"Clin Rheumatol"},{"key":"2022011517444137900_b5","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1002\/art.1780260407","article-title":"Reactivity of serum antibodies to the keratin layer of rat oesophagus in patients with rheumatoid arthritis","volume":"26","author":"Quismorio","year":"1983","journal-title":"Arthritis Rheum"},{"key":"2022011517444137900_b6","first-page":"602","article-title":"Diagnostic value of antikeratin antibodies in rheumatoid arthritis","volume":"11","author":"Ordeig","year":"1984","journal-title":"J Rheumatol"},{"key":"2022011517444137900_b7","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1136\/ard.44.7.446","article-title":"Anti-intermediate filament antibodies, antikeratin antibody, and anti-perinuclear factor in rheumatoid arthritis and infectious mononucleosis","volume":"44","author":"Kataaha","year":"1985","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b8","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1136\/ard.44.7.450","article-title":"Antikeratin antibodies in serum and synovial fluid show specificity for rheumatoid arthritis in a study of connective tissue diseases","volume":"44","author":"Youinou","year":"1985","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b9","first-page":"57","article-title":"Significance of antikeratin antibodies in rheumatoid arthritis","volume":"12","author":"Hajiroussou","year":"1985","journal-title":"J Rheumatol"},{"key":"2022011517444137900_b10","first-page":"607","article-title":"Anticorps anti-Stratum Corneum d'oesophage de rat, autoanticorps anti-k\u00e9ratines \u00e9pidermiques et anti-\u00e9piderme dans la polyarthrite rhumato\u00efde et diverses affections rhumatologiques. Int\u00e9r\u00eat diagnostique, aspects fondamentaux","volume":"53","author":"Serre","year":"1986","journal-title":"Rev Rhum Mal Osteoartic"},{"key":"2022011517444137900_b11","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3109\/03009748709102504","article-title":"Antikeratin antibodies in rheumatoid arthritis. Methods and clinical significance","volume":"16","author":"Kirstein","year":"1987","journal-title":"Scan J Rheumatol"},{"key":"2022011517444137900_b12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1699-0463.1989.tb00775.x","article-title":"Antikeratin antibodies in synovial fluid in rheumatoid arthritis","volume":"97","author":"Kirstein","year":"1989","journal-title":"APMIS"},{"key":"2022011517444137900_b13","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1136\/ard.48.9.712","article-title":"High diagnostic value in rheumatoid arthritis of antibodies to the Stratum Corneum of rat oesophagus epithelium, so-called \u2018antikeratin antibodies","volume":"48","author":"Vincent","year":"1989","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b14","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/978-3-642-76189-8_20","article-title":"The antiperinuclear factor (APF) and antikeratin antibodies (AKA) in rheumatoid arthritis","volume-title":"Rheumatoid arthritis","author":"Hoet","year":"1992"},{"key":"2022011517444137900_b15","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1136\/ard.52.10.749","article-title":"Characterisation of the rat oesophagus epithelium antigens defined by the so-called \u2018antikeratin antibodies\u2019, specific for rheumatoid arthritis","volume":"52","author":"Girbal","year":"1993","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b16","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1172\/JCI116713","article-title":"The cytokeratin filament-aggregating protein filaggrin is the target of the so-called \u2018antikeratin antibodies\u2019, autoantibodies specific for rheumatoid arthritis","volume":"92","author":"Simon","year":"1993","journal-title":"J Clin Invest"},{"key":"2022011517444137900_b17","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/276729a0","article-title":"Assembly of stratum corneum basic protein and keratin filaments in macrofibrils","volume":"276","author":"Dale","year":"1978","journal-title":"Nature (London)"},{"key":"2022011517444137900_b18","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/978-1-4757-9604-9_16","article-title":"Filaggrins","volume-title":"Cellular and molecular biology of intermediate filaments","author":"Dale","year":"1990"},{"key":"2022011517444137900_b19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1111\/1523-1747.ep12464810","article-title":"Natural IgM and IgG autoantibodies to epidermal keratins in normal human sera. I: ELISA titration, immunofluorescence study","volume":"88","author":"Serre","year":"1987","journal-title":"J Invest Dermatol"},{"key":"2022011517444137900_b20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/0896-8411(91)90161-5","article-title":"Natural IgG to epidermal cytokeratins vs IgG to the Stratum Corneum of the rat oesophagus epithelium, so-called \u2018antikeralin antibodies\u2019, in rheumatoid arthritis and other rheumatic diseases","volume":"4","author":"Vincent","year":"1991","journal-title":"J Autoimmun"},{"key":"2022011517444137900_b21","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum"},{"key":"2022011517444137900_b22","first-page":"260","article-title":"Antibodies against human filaggrin that do not recognize its precursor\u2013profilaggrin\u2013in keralohyalin granules","volume":"103","author":"Haftek","year":"1994","journal-title":"J Invest Dermatol"},{"key":"2022011517444137900_b23","first-page":"67","article-title":"Monoclonal anti-thymic cell antibodies detecting epidermal cells","volume":"6","author":"Yonish-Rouach","year":"1984","journal-title":"Thymus"},{"key":"2022011517444137900_b24","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1016\/S0021-9258(19)62353-7","article-title":"Keratin filaments of cultured human epidermal cells","volume":"253","author":"Sun","year":"1978","journal-title":"J Biol Chem"},{"key":"2022011517444137900_b25","first-page":"100","article-title":"A new late differentiation antigen of human cornified epithelia, defined by the monoclonal antibody D40\u201310, characterizes a subpopulation of keratohyalin granules","volume":"2","author":"Mils","year":"1992","journal-title":"Eur J Dermatol"},{"key":"2022011517444137900_b26","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/1523-1747.ep12492589","article-title":"Identification of late differentiation antigens of human cornified epithelia, expressed in re-organized desmosomes and bound to cross-linked envelope","volume":"97","author":"Serre","year":"1991","journal-title":"J Invest Dermatol"},{"key":"2022011517444137900_b27","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1177\/39.11.1717544","article-title":"Immunocytochemical evidence for a possible role of cross-linked keratinocyte envelopes in stratum corneum cohesion","volume":"39","author":"Haftek","year":"1991","journal-title":"J Histochem Cytochem"},{"key":"2022011517444137900_b28","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/BF00371777","article-title":"Keratohyalin granules are heterogeneous in ridged and non-ridged human skin: evidence from anti-filaggrin immunogold labelling of normal skin and skin of autosomal dominant ichthyosis vulgaris patients","volume":"283","author":"G\u00fcnzel","year":"1991","journal-title":"Arch Dermatol Res"},{"key":"2022011517444137900_b29","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1432-0436.1991.tb00241.x","article-title":"Interaction of filaggrin with keratin filaments during advanced stages of normal human epidermal differentiation and in Ichthyosis vulgaris","volume":"48","author":"Manabe","year":"1991","journal-title":"Differentiation"},{"key":"2022011517444137900_b30","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1177\/37.5.2467931","article-title":"Quantitative studies of keratin expression with the post-embedding immunogold labeling method","volume":"36","author":"Haftek","year":"1989","journal-title":"J Histochem Cytochem"},{"key":"2022011517444137900_b31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/1523-1747.ep12494172","article-title":"Interaction of trichohyalin with intermediate filaments: three immunologically defined stages of trichohyalin maturation","volume":"98","author":"O'Guin","year":"1992","journal-title":"J Invest Dermatol"},{"key":"2022011517444137900_b32","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1136\/ard.50.9.611","article-title":"Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin","volume":"50","author":"Hoet","year":"1991","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b33","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1365-2249.1991.tb08124.x","article-title":"The perinuclear factor, a rheumatoid arthritis specific autoantigen, is not present in keratohyalin granules of cultured buccal mucosa cells","volume":"84","author":"Hoet","year":"1991","journal-title":"Clin Exp Immunol"},{"key":"2022011517444137900_b34","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1136\/ard.51.6.743","article-title":"Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis","volume":"51","author":"Paimela","year":"1992","journal-title":"Ann Rheum Dis"},{"key":"2022011517444137900_b35","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1002\/art.1780350810","article-title":"Immunopathology of rheumatoid arthritis: Antikeratin antibodies precede the clinical disease","volume":"35","author":"Kurki","year":"1992","journal-title":"Arthritis Rheum"},{"key":"2022011517444137900_b36","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1111\/j.1365-2249.1990.tb05295.x","article-title":"Soleilhavoup J-P. Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called antikeratin antibodies) in rheumatoid arthritis","volume":"81","author":"Vincent","year":"1990","journal-title":"Clin Exp Immunol"},{"key":"2022011517444137900_b37","first-page":"573","article-title":"Subclass distribution of IgG rheumatoid factor","volume":"29","author":"Cohen","year":"1986","journal-title":"Arthritis Rheum"},{"key":"2022011517444137900_b38","first-page":"41","article-title":"Distribution of IgG subclasses among human autoantibodies to Sm, RNP, dsDNA, SS-B and IgG rheumatoid factor","volume":"23","author":"Yount","year":"1988","journal-title":"Monogr Allergy"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2249.1995.tb03608.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/100\/1\/90\/42202572\/j.1365-2249.1995.tb03608.x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/100\/1\/90\/42202572\/j.1365-2249.1995.tb03608.x.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T17:52:45Z","timestamp":1642269165000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/100\/1\/90\/6484123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,4]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2008,6,28]]},"published-print":{"date-parts":[[2008,6,28]]}},"URL":"https:\/\/doi.org\/10.1111\/j.1365-2249.1995.tb03608.x","relation":{},"ISSN":["1365-2249","0009-9104"],"issn-type":[{"value":"1365-2249","type":"electronic"},{"value":"0009-9104","type":"print"}],"subject":[],"published-other":{"date-parts":[[1995,4]]},"published":{"date-parts":[[1995,4]]}}}