Correlation between anti-mitochondrial antibodies and clinical serological and cirrhotic markers of primary biliary cholangitis / 中华消化杂志

Objective@#To explore the correlation between the level of anti-mitochondrial antibody (AMA) and clinical indicators of first visited primary biliary cholangitis (PBC) patients with positive AMA.@*Methods@#From January 2013 to December 2016, the clinical data of 1 323 patients with positive AMA and/or AMA-M2 detected for the first time were collected through the Information System of Peking University People′s Hospital. Among them, 183 were detected by indirect immunofluorescence assay, 431 were measured by immunoblotting, and 709 were determined by enzyme-linked immunosorbent assay (ELISA). Patients were divided into undiagnosed PBC group (non-PBC group, 973 cases) and newly diagnosed PBC group (new-PBC group, 350 cases including 268 cases of non-liver cirrhosis and 82 cases of liver cirrhosis); among 709 cases detected by ELISA, there were 567 cases in the non-PBC group and 142 cases in the new-PBC group (115 cases of non-liver cirrhosis PBC group and 27 cases of liver cirrhosis PBC group). Among 183 cases determined by indirect immunofluorescence assay, there were 118 cases in the non-PBC group and 65 cases in the new-PBC group. Among them 69 cases with low AMA titer (1∶40—1∶80) (53 cases of non-PBC group and 16 cases of new-PBC group), 95 cases with medium titer (1∶160—1∶320) (59 cases of non-PBC group and 36 cases of new-PBC group) and 19 cases with high titer (≥1∶640) (six cases of non-PBC group and 13 cases of new-PBC group). AMA levels among groups were compared, and its correlation with clinical serology and cirrhosis indicators of PBC including immunoglobulin (Ig)G, IgM, platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptadase (GGT), alkaline phosphatase (ALP), serum total protein, serum albumin, total bilirubin (TBil), total cholesterol (TC), and aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (Fib-4) was analysed. Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were performed for statistical analysis.@*Results@#By ELISA method, the median titer of AMA-M2 of 709 patients was 53 RU/mL, the serum AMA and AMA-M2 levels of new-PBC group were both higher than those of non-PBC group (1∶320 vs. 1∶80, 180 RU/mL vs. 47 RU/mL), and the differences were statistically significant (χ2 = 14.111, Z = -7.531, both P < 0.01). In non-PBC group, the AMA-M2 value was positively correlated with age, serum IgG, IgM, AST, GGT, ALP, serum total protein and TC, all of which were statistically significant (Rho = 0.114, 0.108, 0.337, 0.089, 0.197, 0.086, 0.121 and 0.073, all P<0.05). In new-PBC group, AMA-M2 value was positively correlated with age, IgM, serum total protein and TC, however was negatively correlated with platelet count, all of which were statistically significant (Rho = 0.218, 0.483, 0.230, 0.161, and -0.183, all P<0.05). The median values of serum AMA and AMA-M2 of PBC without liver cirrhosis group were both tended to be lower than those of PBC with liver cirrhosis (1∶160 vs. 1∶320; 174 RU/mL vs. 495 RU/mL), however the differences were not statistically significant (both P>0.05). AMA-M2 value of patients in PBC with liver cirrhosis group was positively correlated with IgM level (r = 0.38, P = 0.039), but was not correlated with APRI and Fib-4 (all P > 0.05). The median of AMA value of 183 patients who underwent indirect immunofluorescence test was 1∶160. In non-PBC group, the IgM levels of patients with low, medium and high AMA titers gradually increased (the median levels were 1.2, 1.7 and 1.8 g/L, respectively); in new-PBC group, the levels of IgM, GGT and ALP of patients with low, medium and high AMA titers gradually increased (median IgM levels were 1.5, 3.7 and 4.1 g/L, respectively; GGT levels were 144, 182 and 317 U/L, respectively; and ALP levels were 137, 168 and 221 U/L, respectively), and the differences were statistically significant (χ2 =6.260, 7.081, 8.030, 15.226, all P<0.05). In non-PBC group, the median level of serum AMA-M2 of men was lower than that of women (41 RU/L vs. 50 RU/L), and the difference was statistically significant (Z = -2.945, P = 0.003). In new-PBC group, the median level of serum AMA-M2 of men tended to be lower than that of women (113 RU/mL vs. 206 RU/mL), but the difference was not statistically significant (P=0.257).@*Conclusion@#Serum AMA level is correlated with many clinical parameters and may be related with the disease severity in patients with PBC.

Situation analysis of timing of first visit of anti-mitochondrial antibody-positive patients / 中华肝脏病杂志

Objective@#To understand the basic information of anti-mitochondrial antibody (anti-AMA)-positive patients after initial diagnosis, and to set groundwork for further exploring the clinical significance of AMA in various diseases.@*Methods@#Demographic data and related clinical information recorded through the Information System of Peking University People's Hospital from January 2013 to December 2016 were collected. Patients whose AMA and/or AMA-M2 first- tested as positive were recorded. Complications were classified according to the International Classification of Diseases.@*Results@#A total of 1323 AMA positive cases were discovered for the first time. Among them, 78.0% were women, and the age of initial diagnosis was 56.8 ± 16.0 years. The first three initially diagnosed departments were rheumatology and immunology (37.4%), liver Disease (15.9%) and hematology (15.9%) relevant to musculoskeletal and connective tissue diseases (45.2%), hematology and hematopoietic organs and immune diseases (30.6%) and circulatory system diseases (29.7%). There were 297 newly confirmed cases of primary biliary cholangitis (PBC); accounting for 89.2% of women, and the age of initial diagnosis was 60.1 ± 12.4 years. The top three departments of initially diagnosed as PBC were liver disease (37.7%), rheumatology (33.0%) and gastroenterology (15.2%), of which 39.7% had musculoskeletal and connective tissue diseases, 27.9% had circulatory diseases, and 24.9 % were combined with endocrine and metabolic diseases.@*Conclusion@#Besides PBC and other autoimmune diseases, AMA and / or AMA-M2 positivity can be observed in a variety of diseases in several clinical departments, and its clinical significance remains to be further clarified.

A novel strategy for cloning and expression of Auto-antigen trimer of M2 Anti-mitochondrial antibody / 国际检验医学杂志

Objective To modify recombinant plasmid construction of BPO trimer,and establish the detec-tion of M2 type anti-mitochondrial antibody (AMA-M2) using ELISA.To modify the recombinant expression vector of the target gene triplet of AMA-M2,and to establish and evaluate an enzyme linked immunosorbent assay (ELISA) for the detection of AMA-M2.Methods The expression vector pGEX 4T 1 BPO was con-structed through the gene amplification of triplet BPO by polymerase chain reaction (PCR),and expressed in E.coli BL21,and the recombinant protein was induced by isopropyl Thioglucoside (IPTG).The target protein was purified by affinity chromatography,and ELISA was established to detect AMA-M2.Results The recom-binant protein with a purity greater than 95% was obtained.326 cases of clinical samples was examined,and in 43 cases of primary biliary cirrhosis (PBC),41 cases showed AMA-M2 positive,the sensitivity was 95.3%(41/43),the specificity was 98.2%(278/283),and the difference of AMA-M2 detection rate between PBC group and non PBC group was statistically significant.Conclusion The target protein obtained by the im-proved technology can be used for AMA-M2 detection.AMA-M2 has high sensitivity and specificity for the clinical diagnosis of PBC.

Clinical value of combined detection of anti-nuclear envelope protein antibody, anti-soluble acid resistant nucleoprotein and anti-mitochondrial antibody M2 subtype in diagnosis sjogren syndrome and primary biliary cirrhosis / 中国综合临床

Objective To investigate the clinical significance of anti-nuclear envelope protein antibody (gp210),anti-soluble acid resistant nucleoprotein (sp100) and anti-mitochondrial antibody M2 subtype (AMA-M2) in sjogren syndrome (SS) and primary biliary cirrhosis (PBC).Methods A total of 241 hospitalized patients diagnosed with connective tissue disease (CTD) were recruited.Anti-gp210,anti-sp100 and AMA-M2 were detected by indirect immunofluorescence.Results (1) Positive rate of AMA-M2,anti-sp100 and antigp210 in 241 cases CTD patient were 10.4％ (25/241),3.3％ (8/241) and 2.9％ (7/241) respectively.(2) There were 16 cases with SS,5 cases with SS-PBC overlap syndrome and 17 cases with PBC in 241 patients with CTD.Distinction among groups of PBC,SS,SS overlapping PBC of positive incidence of AMA-M2 antibody (x2 =6.584,P =0.03) and anti-gp210 (x2 =8.735,P ＜ 0.01) were significantly different,while there was no apparent difference about positive rate of anti-sp100 among the three groups (x2 =3.343,P =0.18).(3) Positive expression of either antibody of anti-gp210 or anti-sp100 in the three groups of SS,SS overlapping PBC,PBC were 3 cases,4 cases,4 cases respectively.The positive rates of any of three autoantibodies in three groups of were 8 cases,5 cases,13 cases respectively.(4) There were significant difference in terms of serum ALB(t =3.858,P＜0.000 1),TSB(t =5.473,P＜0.000 1),ALT(t =2.235,P=0.026),AKP(t =3.141,P =0.002) and γ-GT (t =2.317,P =0.021) in liver damaged patients of all CTD between AMA-M2 positive and negative patients (P ＜ 0.05).However,serum TSB in anti-sp100 positive and negative patients were differed (t =7.892,P ＜ 0.000 1).Serum AKP was different between anti-gp210 positive and negative patients (t =2.451,P =0.015).Conclusion Positive rate of anti-gp210,anti-sp100 and AMA-M2 are the highest in patients with SS overlap of the PBC among CTD patients.Combined detection can improve the sensitivity of diagnosis.Antisp100 and anti-gp210 are valuable for the diagnosis of SS-PBC overlaps syndrome with negative AMA-M2.

Value of serum autoantibodies in the diagnosis of anti-mitochondrial antibody-negative primary biliary cirrhosis / 中华消化杂志

Objective To compare clinical biochemical and pathological characters among antimitochondrial antibody-negative primary biliary cirrhosis (AMA PBC),AMA positive PBC (AMA+ PBC)and autoimmune hepatitis (AIH),and try to find serum biomarkers in the diagnosis of AMA-PBC.Methods From January 2005 to May 2013,23 patients with AMA-PBC,102 patients with AMA+ PBC and 55 patients with AIH were collected.Clinical features of patients were observed.Biochemical indexes (total bilirubin (TBil),direct bilirubin (DBil),alanine aminotransferase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),γ-glutamyltransferase (GGT) and globulin) were tested.Immunological indexes immunoglobulin ((Ig)G,IgM and IgA) were also measured.Antinuclear amibody,anti smooth muscle antibody (SMA) and AMA were detected by indirect immunofluorescence.Soluble acidic phosphorylation nucleoprotein antibody and anti-nuclear membrane glycoprotein antibody were detected by Western blotting.Non parameter test was for non normal distributed measurement data and grade data comparison.The cut off value,sensitivity and specificity of IgM in the diagnosis of PBC were calculated with receiver operating characteristic (ROC) curve.The sensitivity and specificity of soluble acidic phosphorylation nucleoprotein antibody and anti-nuclear membrane glycoprotein antibody in the diagnosis of PBC were analyzed with fourfold table.Results The rates of fatigue and jaundice of AMA-PBC group (39.1％,9/23 ; 43.5 ％,10/23) were both higher than those of AIH group (16.4 ％,9/55; 14.5 ％,8/55),and the differences were statistically significant (x2 =4.735 and 7.648,both P＜ 0.05).The levels of ALP and GGT of AMA PBC group were higher than those of AIH group,and the levels of ALT and AST were lower than those of AIH group (Z=-4.577,-4.257,-2.820 and -2.055,all P＜0.05).The level of IgM of AMA PBC group (417(270,610) mg/L) was higher than that of AIH group (97(69,195) mg/L),however lower than that of AMA+ PBC group (546(419,704) mg/L),and the differences were statistically significant (Z=-4.362 and-0.210,both P＜0.05).The level of IgG of AMA PBC group was lower than that of AIH group (Z=-2.202,P＜0.05).The positive rates of antinuclear antibody and SMA of AMA PBC group (95.7％ (22/23),8.7％ (2/23)) were both higher than those of AMA+ PBC group (33.3％(34/102),1.0％(1/102)),and the differences were statistically significant (x2 =29.474 and 4.769,both P＜0.05).The positive rates of soluble acidic phosphorylation nucleoprotein antibody and anti nuclear membrane glycoprotein antibody of AMA PBC group (60.9％,14/23; 30.4％,7/23) were both higher than those of AIH group (2.0％,1/55; 0),and the differences were statistically significant (x2=36.409 and 24.329,both P＜0.05).The karyotype of antinuclear antibody of AMA PBC and AMA+ PBC group mainly was granules pattern (60.9 ％,14/23;75.5％,77/102),however of AIH group was mainly homogeneous pattern (38.2％,21/55).If the cut off value of IgM was 277 mg/L,the sensitivity and specificity of IgM in the diagnosis of PBC was 72.2％ and 94.4 ％.The sensitivity and specificity of soluble acidic phosphorylation nucleoprotein antibody in the diagnosis of PBC was 24.1％ and 97.2％.The sensitivity and specificity of anti-nuclear membrane glycoprotein antibody was 35.2 ％ and 100.0 ％.The sensitivity and specificity of any one of anti-nuclear membrane glycoprotein antibody positive,soluble acidic phosphorylation nucleoprotein antibody positive or IgM＞277 mg/L in the diagnosis of PBC was 88.9％ and 94.4％.Conclusions AMA-PBC and AMA+ PBC have similar clinical manifestations and serum biochemical test results.Antinuclear antibody and/or SMA positive is the feature of AMA-PBC and which should be distinguished with AIH.The sensitivity and specificity of any one of the followiags:anti nuclear membrane glycoprotein antibody positive,soluble acidic phosphorylation nucleoprotein antibody positive or IgM＞277 mg/L is high in the diagnosis of PBC.

Clinical significance of anti-mitochondrial antibodies in a patient with chronic graft-versus-host disease following hematopoietic stem cell transplantation

Recent studies indicate that patients with chronic graft-versus-host disease (GVHD) are not expected to show positivity for anti-mitochondrial antibody (AMA), which is a specific disease marker for primary biliary cirrhosis (PBC). A differential diagnosis between PBC and hepatic involvement of GVHD based on clinical manifestations and pathologic study is difficult because both diseases show similar results. Therefore, the presence of AMA may be important for distinguishing each disease. Here, we report a case of hepatic involvement of chronic GVHD with positive AMA, in which the pathologic findings and initial presentation of clinical findings were compatible with both PBC and chronic GVHD.

Expression of costimulating factor B7-H4 in patients with primary billary cirrhosis / 中华微生物学和免疫学杂志

Objective To study the relationship between the expression of eostimulating factor B7-H4 in patients with primary biliary cirrhosis (PBC) and the pathogenesis of PBC. Methods The expression of B7-H4 mRNA on peripheral blood mononuclear cell (PBMC) of 65 patients with PBC was tested by real-time PCR. Serum levels of IL-2 were assayed by ELISA. CD4+, CD8+ T lymphocytes expression level and B7-H4 expression rate before and after activation were measured by three-color flow cytometry (FCM). Re-sults (1) Expression of B7-H4 mRNA and BT-H4 percentage in PBC group were significantly lower than that in none-PBC group and healthy controls(P<0.01);(2)After 72 h activation, the percentage of CD4+, CD8+, and CD4+ CD8+T lymphoeytes and serum levels of IL-2 decreased (P<0.05), and the percentage of CD4+, CD4+ CD8+T lymphocytes and serum levels of IL-2 were significantly higher than that of none-PBC group and healthy controls(P<0.01);(3)Levels of alanine aminotransferase(ALT), aspartate amin-otransferase(AST), alkaline phosphatase(ALP) and γ-glutamyl transpeptidase(GGT) of patients with posi-tive anti-mitochondrial antibody(AMA)-M2 rose. There was no significant difference of B7-H4 expressions on T cells between patients either with or without AMA-M2 antibody. Conclusion The costimulating factor B7-H4 can express on T lymphocytes which is activated by phytohemagglatinin(PHA) aad plays a negative role on T cells responses.

Determination of Anti-mitochondrial Antibody with M2 Antigens / 대한진단검사의학회지

BACKGROUND: Anti-mitochondrial antibodies (AMA) are a hallmark of primary biliary cirrhosis (PBC); however, low titers of AMA are also detected in some patients without PBC. We evaluated the clinical value of commercial rat kidney/stomach sections and an additional biochip coated with mitochondrial antigen M2 (pyruvate dehydrogenase complex). METHODS: A total of 124 patients who had been tested for AMA were evaluated. Results of AMA, antibodies to M2, and antinuclear antibody were reviewed retrospectively and searched for clinical and laboratory data to diagnose PBC. AMA and M2 antibody were assayed by an indirect immunofluorescence assay using EUROPLUS kit (Euroimmun, Luebeck, Germany). RESULTS: In 10 of the 124 patients, a diagnosis of PBC was established by AMA, liver function test or liver biopsy. The sensitivity and specificity of rat kidney/stomach section, M2 antibody, and coarse cytoplasmic fluorescent pattern of HEp-2 cell were 80.0, 75.0, 88.9% and 97.4, 98.2, 97.3%, respectively; however, these differences were not statistically significant. Six patients with coarse cytoplasmic pattern of HEp-2 cell at 1: 320 dilution were positive for both rat kidney/stomach sec-tion and M2 antibody. Two of five patients with coarse cytoplasmic pattern at below 1: 80 dilution were diagnosed as PBC, yet all of them were negative for M2 antibody. CONCLUSIONS: M2 biochip test would be convenient to test simultaneously with rat kidney/stomach section and it provided results similar to those of the preexisting serological tests for PBC.

A Prospective Study on the Prevalence and Clinical Significance of Autoantibodies in Patients with Suspected Nonalcholic Fatty Liver Disease / 대한간학회지

BACKGROUND/AIMS: Exclusion of liver disease from other causes such as autoimmune hepatitis is necessary for diagnosis of nonalcoholic fatty liver disease (NAFLD). However, there has been no study on the prevalence and significance of autoantibodies in the patients with clinically suspected NAFLD in Korea, where hepatitis B is endemic and autoimmune hepatitis is relatively uncommon. METHODS: We prospectively tested for anti-nuclear antibody (ANA), anti-smooth muscle antibody (ASMA), and anti-mitochondrial antibody (AMA) in 135 serially enrolled patients with suspected NAFLD. We compared the clinical characteristics and biochemical indices of the ANA-positive or ASMA-positive group with those of the autoantibody-negative group. RESULTS: Sixteen patients (11.8%) had serum autoantibodies; there was ANA in 8 patients (5.9%), ASMA in 7 (5.1%), and AMA in 2 (1.5%). Both ANA and AMA were positive in one patient. The ANA-positive or ASMA-positive group showed an older age (49.5+/-13.0 vs. 42.0+/-10.9 years, respectively, P=0.018) and higher levels of serum globulin (3.1+/-0.4 vs. 2.9+/-0.4 g/dL, respectively, P=0.037), compared with the autoantibody-negative group. Two cases with positive ANA or ASMA fulfilled the diagnostic criteria for probable autoimmune hepatitis and two cases with positive AMA were suspected as primary biliary cirrhosis. CONCLUSIONS: These findings suggest that autoantibodies could be found in some patients with suspected NAFLD in Korea, AMA-positivity or ASMA-positivity could be associated with old age and high serum globulin, and some of the autoantibody-positive cases could be diagnosed as autoimmune hepatitis or primary biliary cirrhosis. Further studies are necessary to clarify the clinical significance of autoantibody positivity in those patients.

Detection of autoantibodies in 60 patients with primary biliary cirrhosis / 中国实用内科杂志

Objective To study the types of autoantibodies in patients with primary biliary cirrhosis.Methods There were 60 patients with primary biliary cirrhosis from January 1995 to December 2004 in People's Hospital. We analyzed those patients' autoantibodies results and clinical data.Results There were 75% patients with anti-mitochondrial antibody(45/60),and antinuclear antibodies were detected in 60%(36/60)PBC patients,with the following hierarchy of specificities:23%(14/60)speckled,20%(12/60)multiple nuclear dots,16%(10/60)nuclear membranous,6%(6/60)anti-centromere,1.6%(1/60)homogeneous,20%(12/60)anti-SSA,10%(6/60)anti-SSB and 1.6%(1/60)anti-RNP. Several patients showed multiple specificities. Comparing PBC patients with or without AMA,no statistically significant difference was found on ages,biochemical and immunological parameters.Conclusion AMA-negative PBC patients share the same clinical features with AMA-passive PBC. Except for AMA,other antibodies may present in PBC patients. Multiple nuclear dots and nuclear member antinuclear antibodies may be helpful for diagnosing PBC patients without AMA.

Clinical features of 70 patients with primary biliary cirrhosis / 中华消化杂志

Objective Clinical features of primary biliary cirrhosis (PBC) were reviewed in order to improve its diagnosis in our clinical practice. Methods Clinical data of 70 patients with PBC were reviewed including the clinical manifestation, laboratory tests, pathological findings and the response to therapy. Results Sixty-two patients were females (88.6%), eight patients were males (11.4%), and the mean age at diagnosis was (53.1?10.4) years. The most frequently complained symptoms were pruitus (60.0%), fatigue (42.9%), anorexia (41.4%) and jaundice (45.7%). Serum alkaline phosphatase (ALP) and ? glutamyl transpeptidase (GGT) levels were markedly elevated in all patients, while alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were mildly elevated. The serum total bilirubin level increased in sixty-five patients (92.9%). Forty-four patients (62.9%) had elevated serum immunoglobin M (IgM), and 98.6% of patients (69/70) were antimitochondrial antibody (AMA) /AMA-M2 positive. Forty-one patients underwent pathological examinations, 82.9% in early stage (Ⅰ,Ⅱ stage) and 17.1% in advanced stage (Ⅲ,Ⅳ stage).Conclusions PBC most frequently affects middle-aged women and the main clinical manifestations are pruritus, fatigue, anorexia and jaundice. The elevated level of ALP, GGT, IgM and positive AMA/AMA-M2 may be crucial to diagnosis of PBC.

Clinical analysis of primary biliary cirrhosis: a report of 31 cases / 中华消化杂志

Objective Clinical features of primary biliary cirrhrosis(PBC) were reviewed in order to improve its diagnosis and treatment. Method The general conditions, clinical manifestations, biochemical and immunological changes, and pathological findings were assessed in 31 patients. Result Twenty five cases were females, the mean age at definite diagnosis was (49.2?10.7)years. Jaundice(74.2%) was the most frequent symptoms, pruritus (51.6%) and fatigues (32.3%)were the second and thrid, respectively. Three patients (9.7%)were complicated by ascites. Serum alkline phosphatase (ALP) , glutamyl transpeptidase (? GT) and bilirubin levels were markedly elevated ((388.9?277.5)U/L, (381.6?213.2)U/L and( 176.4 ?176.1)?mol/ L, respectively).ALT and AST levels were mildly or moderately elevated ((79.7?46.3) U/L and(119.8?61.2)U/L, respectively),mean level of IgM was also elevated to (3.0?1.9)g/L. 92% (23/25) of patients had positive anti mitochondrial antibody(AMA). Ursodeoxycholic acid (UDSA) was efficitive in 61.3% of patients. Conclusions PBC most frequently affects middle aged women. The elevated level of ALP, ? GT and IgM and AMA positive may be crucial to diagnosis of PBC. Liver biopsy can help to identify the diagnosis and carry on pathological staging.

Clinicopathologic Comparison between Autoimmune Cholangitis and Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is characterized by histological findings of an immunoinflammatory destruction of small- and medium-sized bile ducts with progressive portal fibrosis, and the presence of anti-mitochondrial antibody (AMA) with a laboratory evidence of chronic cholestasis. The term "autoimmune cholangitis" (AIC) is used for a disease with the clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative AMA and positive anti-nuclear antibody (ANA) tests. Eight cases of AIC and ten cases of PBC were reviewed in order to determine whether there was any difference between two diseases in clinico-pathologic aspects. All of the patients were female and the mean ages of AIC and PBC patients were 48 and 47 years, respectively. ANA test was positive in six of ten PBC paients and their mean titer was lower than that of AIC patients. IgM level was significantly higher in PBC group than in AIC group. No significant difference was found between two groups with respect to biochemical and histopathological features. Since the only consistently distinguishing features between these two conditions are the autoantibody profile (AMA vs ANA) and immunoglobulin level (IgM), these two conditions might be part of a spectrum. PBC can be considered to be the same as AMA-positive AIC or alternatively AIC to be the same as AMA-negative PBC.