{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T21:17:12Z","timestamp":1773955032450,"version":"3.50.1"},"reference-count":30,"publisher":"BMJ","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1994,2]]},"abstract":"<jats:p>This study reports on a group of 20 patients with an initial diagnosis of primary biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial antibodies by immunofluorescence. All had a clinical history compatible with primary biliary cirrhosis, and results of biochemical, histological, and radiological investigations were consistent with this diagnosis despite the absence of antimitochondrial antibodies by immunofluorescence. For comparison, these patients were matched for sex and serum bilirubin with 20 antimitochondrial antibody positive (&gt; 1:160) and histologically confirmed primary biliary cirrhosis patients who served as controls. Serum samples from both groups were retested blindly for antimitochondrial antibodies using immunoblotting and for antibodies to the major M2 mitochondrial autoantigens by enzyme linked immunosorbent assay (ELISA). Three antimitochondrial antibody immunofluorescence negative patients had antimitochondrial antibodies by immunoblotting and ELISA; the remaining 17 patients were confirmed negative by all methods. The antimitochondrial antibody immunofluorescence positive controls were verified by immunoblotting or ELISA, or both. All 17 patients negative for antimitochondrial antibodies had antinuclear antibodies, often in high titres, compared with 3\/17 of the antimitochondrial antibody positive controls (p = 0.0001). Additionally, the antimitochondrial antibody negative group also had significantly higher smooth muscle antibody titres (p = 0.03) and lower serum IgM (p = 0.01) and aspartate aminotransferase (p = 0.03) activities than the antimitochondrial antibody positive controls. Analysis of clinical findings, histological tests, serum bilirubin, alkaline phosphatase, alanine aminotransferase, and IgG, disclosed no significant differences between the two groups. This paper describes a group of patients with the clinical and histological features of PBC but who do not fulfil the usual criteria necessary to make this diagnosis. Because they also have very high titres of antinuclear antibodies, smooth muscle antibodies, and comparatively low IgM and aspartate aminotransferase activities, we believe they are distinct from PBC and have a syndrome of autoimmune cholangitis.<\/jats:p>","DOI":"10.1136\/gut.35.2.260","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"260-265","source":"Crossref","is-referenced-by-count":183,"title":["Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis."],"prefix":"10.1136","volume":"35","author":[{"given":"P","family":"Michieletti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I R","family":"Wanless","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Katz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P J","family":"Scheuer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S J","family":"Yeaman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M F","family":"Bassendine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E J","family":"Heathcote","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1994,2,1]]},"reference":[{"key":"ref_1","first-page":"827","article-title":"Serological tests in diagnosis of primary biliary cirrhosis","volume":"i:","author":"Walker, J.G.; Doniach, D.; Roitt, I.M.; Sherlock, S.","year":"1965","unstructured":"Walker JG, Doniach D, Roitt IM, Sherlock S. Serological tests in diagnosis of primary biliary cirrhosis. Lancet 1965; i: 827-","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1136\/jcp.19.6.527","article-title":"Serological and histological diagnosis of primary biliary cirrhosis","volume":"19","author":"Goudie, R.B.; MacSween, R.N.M.; Goldberg, D.M.","year":"1966","unstructured":"Goudie RB, MacSween RNM, Goldberg DM. Serological and histological diagnosis of primary biliary cirrhosis. Clin Pathol 1966; 19: 527-38.","journal-title":"Clin Pathol"},{"key":"ref_3","first-page":"533","article-title":"Mitochondrial antibody in primary biliary cirrhosis and other diseases","volume":"77","author":"Klatskin, G.; Kantor, F.S.","year":"1972","unstructured":"Klatskin G, Kantor FS. Mitochondrial antibody in primary biliary cirrhosis and other diseases. Ann Intern Med 1972; 77: 533-41."},{"key":"ref_4","first-page":"1067","article-title":"Primary biliary cirrhosis - identification of two major mitochondrial autoantigens","volume":"i:","author":"Yeaman, S.J.; Fussey, S.P.M.; Danner, D.J.; James, O.F.W.; Mutimer, D.J.; Bassendine, M.F.","year":"1988","unstructured":"Yeaman SJ, Fussey SPM, Danner DJ, James OFW, Mutimer DJ, Bassendine MF. Primary biliary cirrhosis - identification of two major mitochondrial autoantigens. Lancer 1988; i: 1067-70.","journal-title":"Lancer"},{"key":"ref_5","first-page":"73","article-title":"Primary biliary cirrhosis: nature of autoantigens. Sprneger Sernin Immunopathol","volume":"12","author":"Bassendine, M.F.; Yeaman, S.J.","year":"1990","unstructured":"Bassendine MF, Yeaman SJ. Primary biliary cirrhosis: nature of autoantigens. Sprneger Sernin Immunopathol 1990; 12: 73-"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1016\/0016-5085(90)90488-M","article-title":"Primary biliary cirrhosis: quantitation of autoantibQdies to purified mitochondrial enzymes and correlation with disease progression","volume":"99","author":"Heseltine, L.; Turner, I.B.; Fussey, S.P.M.; Kelly, P.J.; James, O.F.W.; Yeaman, S.J.","year":"1990","unstructured":"Heseltine L, Turner IB, Fussey SPM, Kelly PJ, James OFW, Yeaman SJ, et al. Primary biliary cirrhosis: quantitation of autoantibQdies to purified mitochondrial enzymes and correlation with disease progression. Gastroenterology 1990; 99:1786-92.","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1056\/NEJM198905253202104","article-title":"Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis","volume":"320","author":"de Water J, Van; A, Cooper; CD, Surh; R, Coppel; D, Danner; A, Ansari","year":"1989","unstructured":"Van de Water J, Cooper A, Surh CD, Coppel R, Danner D, Ansari A, et al. Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. N EnglJ Med 1989; 320: 1377-80.","journal-title":"N EnglJ Med"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1002\/hep.1840150302","article-title":"Use ofdesigner recombinant mitochondrial antigens in the diagnosis of primary biliary cirrhosis","volume":"15","author":"Leung, P.S.; Iwayama, T.; Prindiville, T.; Chuang, D.T.; Ansari, A.A.; Wynn, R.M.; etal","year":"1992","unstructured":"Leung PS, Iwayama T, Prindiville T, Chuang DT, Ansari AA, Wynn RM, etal. Use ofdesigner recombinant mitochondrial antigens in the diagnosis of primary biliary cirrhosis. Hepatology 1992; 15: 367-72.","journal-title":"Hepatology"},{"issue":"39","key":"ref_9","first-page":"587","article-title":"Quantitative studies of immunofluorescent staining","volume":"1968","author":"Beutner, E.H.; Sepulveda, M.R.; Barnett, E.V.","unstructured":"Beutner EH, Sepulveda MR, Barnett EV. Quantitative studies of immunofluorescent staining. Bull World Health Organ 1968; 39:587.","journal-title":"Bull World Health Organ"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1042\/bj1910147","article-title":"Purification of 2-oxo acid dehydrogenase multienzyme complexes from ox heart by a new method","volume":"191","author":"Stanley, C.J.; Perham, R.N.","year":"1980","unstructured":"Stanley CJ, Perham RN. Purification of 2-oxo acid dehydrogenase multienzyme complexes from ox heart by a new method. BiochemJ 1980; 191: 147-54.","journal-title":"BiochemJ"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8654","DOI":"10.1073\/pnas.85.22.8654","article-title":"Identification and analysis of the major M2 antigens in primary biliary cirrhosis","volume":"85","author":"Fussey, S.P.M.; Guest, JR, James; OFW, Bassendine; MF, Yeaman; S.J.","year":"1988","unstructured":"Fussey SPM, Guest JR, James OFW, Bassendine MF, Yeaman SJ. Identification and analysis of the major M2 antigens in primary biliary cirrhosis. Proc Natl Acad Sci USA 1988; 85: 8654-8.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_12","first-page":"57599","article-title":"Maturation of the head of bacteriophage T4: DNA packaging events","volume":"80","author":"Laemmli, U.K.; Favre, M.","year":"1973","unstructured":"Laemmli UK, Favre M. Maturation of the head of bacteriophage T4: DNA packaging events.J MolBiol 1973; 80: 57599.","journal-title":"J MolBiol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/hep.1840130314","article-title":"Autoantibodies in primary biliary cirrhosis: analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes","volume":"13","author":"Fussey, S.P.M.; Lindsay, J.G.; Fuller, C.; Perham, R.N.; Dale, S.; James, O.F.W.","year":"1991","unstructured":"Fussey SPM, Lindsay JG, Fuller C, Perham RN, Dale S, James OFW, et al. Autoantibodies in primary biliary cirrhosis: analysis of reactivity against eukaryotic and prokaryotic 2-oxo acid dehydrogenase complexes. Hepatology 1991; 13: 467-74.","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/BF00432479","article-title":"Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis)","volume":"379","author":"Ludwig, J.; ER, Dickson; GSA, McDonald","year":"1978","unstructured":"Ludwig, J, Dickson ER, McDonald GSA. Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch [A] 1978; 379: 103-12.","journal-title":"Virchows Arch [A]"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1177\/000456327000700405","article-title":"Immunological tests in liver disease","volume":"7","author":"Walker, J.G.","year":"1970","unstructured":"Walker JG. Immunological tests in liver disease. Ann Clin Biochem 1970; 7: 93-6.","journal-title":"Ann Clin Biochem"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1093\/ajcp\/70.3.352","article-title":"Immunoglobulin concentrations and autoantibody titres in diseases of the liver and biliary tree","volume":"70","author":"Ward, A.M.; Ellis, G.; Goldberg, D.M.","year":"1978","unstructured":"Ward AM, Ellis G, Goldberg DM. Immunoglobulin concentrations and autoantibody titres in diseases of the liver and biliary tree. AmJ Clin Pathol 1978; 70: 352-8.","journal-title":"AmJ Clin Pathol"},{"key":"ref_17","first-page":"553","article-title":"Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis","volume":"55","author":"Bernstein, R.M.; Neuberger, J.M.; Bunn, C.C.; Calendar, M.E.; Hughes, G.R.; Williams, R.","year":"1984","unstructured":"Bernstein RM, Neuberger JM, Bunn CC, Calendar ME, Hughes GR, Williams R. Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis. Clin ExpImmunol 1984; 55: 553-60.","journal-title":"Clin ExpImmunol"},{"key":"ref_18","first-page":"288","article-title":"Antinuclear antibodies in primary biliary cirrhosis","volume":"i:","author":"Powell, F.; Schroeter, A.L.; Dickson, E.R.","year":"1984","unstructured":"Powell F, Schroeter AL, Dickson ER. Antinuclear antibodies in primary biliary cirrhosis. Lancet 1984; i: 288-9.","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/0016-5085(90)91246-3","article-title":"Antinuclear antibodies directed to a 200kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis","volume":"99","author":"Lassoued, K.; Brenard, R.; Degos, F.; Courvalin, J.C.; Andre, C.; Danon, F.","year":"1990","unstructured":"Lassoued K, Brenard R, Degos F, Courvalin JC, Andre C, Danon F, et al. Antinuclear antibodies directed to a 200kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis. Gastroenterology 1990; 99: 181-6.","journal-title":"Gastroenterology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1002\/hep.1840080438","article-title":"Antibodies against nuclear envelope-associated proteins in primary biliary cirrhosis","volume":"8","author":"Lozano, F.; Pares, A.; Borche, L.; Plana, M.; Gallart, T.; Rodes, J.","year":"1988","unstructured":"Lozano F, Pares A, Borche L, Plana M, Gallart T, Rodes J, et al. Antibodies against nuclear envelope-associated proteins in primary biliary cirrhosis. Hepatology 1988; 8: 930-8.","journal-title":"Hepatology"},{"key":"ref_21","first-page":"433847","article-title":"Isolation and characterisation ofcDNA encoding a human nuclear antigen predominantly recognised by autoantibodies from patients with primary biliary cirrhosis","volume":"145","author":"Szostecki, C.; Guldner, H.H.; Netter, H.J.; Wills, H.","year":"1990","unstructured":"Szostecki C, Guldner HH, Netter HJ, Wills H. Isolation and characterisation ofcDNA encoding a human nuclear antigen predominantly recognised by autoantibodies from patients with primary biliary cirrhosis. J Immunol 1990; 145: 433847.","journal-title":"J Immunol"},{"key":"ref_22","first-page":"143","article-title":"Histopathological features in mixed types of chronic aggressive hepatitis and primary biliary cirrhosis","volume":"373","author":"Kloppel, G.; Seifert, G.; Lindner, H.; Dammermann, R.; Sack, H.J.; Berg, P.A.","year":"1977","unstructured":"Kloppel G, Seifert G, Lindner H, Dammermann R, Sack HJ, Berg PA. Histopathological features in mixed types of chronic aggressive hepatitis and primary biliary cirrhosis. VirchowsArch[Al 1977; 373: 143-60.","journal-title":"VirchowsArch[Al"},{"key":"ref_23","first-page":"775","article-title":"Chronic active hepatitis with histological features of primary biliary cirrhosis","volume":"32","author":"Okuno, T.; Seto, Y.; Okanoue, T.; Takino, T.","year":"1987","unstructured":"Okuno T, Seto Y, Okanoue T, Takino T. Chronic active hepatitis with histological features of primary biliary cirrhosis. DigDisSci 1987; 32: 775-9.","journal-title":"DigDisSci"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1055\/s-2008-1040444","article-title":"A 33-year old woman with an autoimmune syndrome","volume":"ii:","author":"Carrougher, J.G.; Usa, M.; Shaffer, R.T.","year":"1991","unstructured":"Carrougher JG, Usa M, Shaffer RT. A 33-year old woman with an autoimmune syndrome. Semin Liver Dis 1991; ii: 256-62.","journal-title":"Semin Liver Dis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0168-8278(88)80482-3","article-title":"Idiopathic adulthood ductopenia: a cause of chronic cholestatic liver disease and biliary cirrhosis","volume":"7","author":"Ludwig, J.; Wiesner, R.H.; LaRusso, N.F.","year":"1988","unstructured":"Ludwig J, Wiesner RH, LaRusso NF. Idiopathic adulthood ductopenia: a cause of chronic cholestatic liver disease and biliary cirrhosis. J Hepatol 1988; 7: 193-9.","journal-title":"J Hepatol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/00004836-198003000-00008","article-title":"Atypical biliary cirrhosis - or sclerosing cholangitis","volume":"2","author":"Galambos, J.T.; Brooks, W.S.","year":"1980","unstructured":"Galambos JT, Brooks WS. Atypical biliary cirrhosis - or sclerosing cholangitis. J Clin Gastroenterol 1980; 2: 43-52.","journal-title":"J Clin Gastroenterol"},{"key":"ref_27","first-page":"1420","article-title":"Idiopathic adulthood ductopenia presenting with chronic recurrent cholestasis","volume":"12","author":"Faa, G.; Van Eyken, P.; Demelia, L.; Vallebona, E.; Costa, V.; Desmet, V.J.","year":"1991","unstructured":"Faa G, Van Eyken P, Demelia L, Vallebona E, Costa V, Desmet VJ. Idiopathic adulthood ductopenia presenting with chronic recurrent cholestasis. J Hepatol 1991; 12: 1420.","journal-title":"J Hepatol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1016\/0016-5085(90)90494-L","article-title":"Idiopathic biliary ductopenia in adults: a report of five cases","volume":"99","author":"Zafrani, E.S.; Metreau, J.-M.; Douvin, C.; Larrey, D.; Massari, R.; Reynes, M.","year":"1990","unstructured":"Zafrani ES, Metreau J-M, Douvin C, Larrey D, Massari R, Reynes M, et al. Idiopathic biliary ductopenia in adults: a report of five cases. Gastroenterology 1990; 99: 1823-8.","journal-title":"Gastroenterology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1055\/s-2008-1068269","article-title":"Ein der chronish-destruierenden nichteitrigen Cholangitis ahnliches Krankheitsbild mit Antikorpern (immuncholangitis)","volume":"112","author":"Brunner, G, Klinge 0","year":"1987","unstructured":"Brunner G, Klinge 0. Ein der chronish-destruierenden nichteitrigen Cholangitis ahnliches Krankheitsbild mit Antikorpern (immuncholangitis). Dtsch Med Wochenschr 1987; 112: 1454-8.","journal-title":"Dtsch Med Wochenschr"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4049\/jimmunol.146.1.89","article-title":"Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response ofprimary biliary cirrhosis","volume":"146","author":"de Water J, Van; AA, Ansari; CD, Surh; R, Coppel","year":"1991","unstructured":"Van de Water J, Ansari AA, Surh CD, Coppel R, et al. Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response ofprimary biliary cirrhosis. J Immunol 1991; 146: 89-94.","journal-title":"J Immunol"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.35.2.260","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T21:28:07Z","timestamp":1757280487000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.35.2.260"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,2]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1994,2,1]]},"published-print":{"date-parts":[[1994,2]]}},"alternative-id":["10.1136\/gut.35.2.260"],"URL":"https:\/\/doi.org\/10.1136\/gut.35.2.260","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,2]]}}}