Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

OBJECTIVETo evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy.

METHODSThe clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test.

RESULTSThere was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05).

CONCLUSIONSP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Adult ; Aged ; Antibodies, Antinuclear ; blood ; Antigens, Nuclear ; immunology ; Autoantibodies ; blood ; Autoantigens ; immunology ; Female ; Humans ; Liver ; pathology ; Liver Cirrhosis, Biliary ; immunology ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo observe the efficacy of ursodeoxycholic acid (UDCA) combined with Tongdan: Decoction () on immunological indices and histopathological changes in patients with primary biliary cirrhosis (PBC) of IIor III histological stage.

METHODSSixty PBC patients were assigned randomly and equally: to the control group treated with UDCA alone and the treatment group treated with UDCA combined with Tongdan Decoction. The immunological indices and histopathological changes were detected before and after 24-week treatment, and the follow-up lasted for 1-3 years.

RESULTSAfter 24-week treatment, CD4(+)CD28(-) in the peripheral blood was lowered and CD4(+)CD25(+) was increased in both groups, and better effect was shown in the treatment group (P<0.01). The levels of IgM, IgG, and IgA decreased markedly after 96-week treatment in the treatment group (P< 0.05, P< 0.01), while in the control group, only the latter two showed significant decrease after 148 week (all P<0.05). At the end of the 3-year follow-up, the medians of histopathological

CONCLUSIONCombined therapy of Tongdan Decoction and UDCA showed a better therapeutic effect: than UDCA monotherapy on PBC, especially in improving immunological indices and histopathological hepatic changes.

Antigens, CD ; blood ; Biomarkers ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Immunoglobulin G ; blood ; Inflammation ; blood ; complications ; Liver Cirrhosis, Biliary ; blood ; drug therapy ; immunology ; pathology ; Male ; Middle Aged ; Ursodeoxycholic Acid ; therapeutic use

OBJECTIVETo investigate the correlation between ER-a in the liver and cytokines of T lymphocytes subsets and serum signatures in PBC patients.

METHODSThe research is performed with cross-sectional study. 80 PBC women patients without treatment were enrolled in PBC group, 10 healthy women as baseline-matched in healthy-control group, and 20 patients with non-autoimmune liver disease in non-PBC control group. The expression of IL-6, IL-8, IL-22, TNFa, IFNgamma, AMA-M2, Sp100 and gp210 were analyzed in Peripheral Blood using ELISA in all groups, and ER-a of patients were performed on tissues from liver biopsies in PBC group and non-PBC control group with immunohistochemistry. Spearman correlation test were performed on the indices to identified the association of all Parameters. numerical data were compared with Wilcoxon rank-sum test.

RESULTSCompared with healthy-control group, expression of serum cytokines are significantly higher in PBC and non-PBC groups (P less than 0.01), while no significant difference were observed between PBC and non-PBC groups. The positive rate of ER-a in PBC patients liver tissues in PBC group is higher than that in non-PBC group (Z=4.82, P less than 0.01). Expression of ER-a is positively correlated with positive rates of AMA-M2 antibody, Sp100 and gP210 of tissues of PBC patients ( r=0.898, 0.819, 0.814, P less than 0.01). ER-a is positive correlated with the expression of cytokines, among which the coefficient of correlation of IL-22, TNFa, IFNgamma is more than 0.7 (r=0.71, 0.89, 0.82, P less than 0.01), AMA-M2, Sp100, gp210 is negative in serum of non-PBC control group. No obviously correlations were indicated between the expression of ER-a and cytokines.

CONCLUSIONA high level of expression of cytokines in the serum might be one of the factors of etiopathogenesis of PBC.

Autoantibodies ; blood ; Biomarkers ; blood ; Case-Control Studies ; Estrogen Receptor alpha ; metabolism ; Female ; Humans ; Interleukin-6 ; blood ; Interleukin-8 ; blood ; Interleukins ; blood ; Liver ; metabolism ; Liver Cirrhosis, Biliary ; blood ; immunology ; Middle Aged

Primary biliary cirrhosis (PBC) is a slowly progressive cholestatic liver disease of autoimmune etiology. The initial presentation of PBC is various from asymptomatic, abnormal liver biochemical tests to overt cirrhosis. The diagnosis of PBC is based on cholestatic biochemical liver tests, presence of antimitochondrial antibody and histologic findings of nonsuppurative destructive cholangitis. Although the diagnosis is straightforward, it could be underdiagnosed because of its asymptomatic presentation, or underrecognition of the disease. UDCA in a dose of 13-15 mg/kg is the widely approved therapy which can improve the prognosis of patients with PBC. However, one-third of patients does not respond to UDCA therapy and may require liver transplantation. Every effort to diagnose PBC in earlier stage and to develop new therapeutic drugs and clinical trials should be made.
Autoantibodies/blood ; Autoimmunity/immunology ; Cholagogues and Choleretics/therapeutic use ; Humans ; Liver Cirrhosis, Biliary/*diagnosis/pathology/*therapy ; Liver Transplantation ; Ursodeoxycholic Acid/therapeutic use

Autoimmunity ; Humans ; Immunity, Innate ; Liver Cirrhosis, Biliary ; immunology

OBJECTIVETo explore the clinical and pathological features of primary biliary cirrhosis (PBC) patients with negative anti-mitochondria antibody (AMA).

METHODSTwo hundreds and eight PBC patients were enrolled. The clinical and histological data of the negative AMA cases were compared with the AMA/AMA-M2 positive cases.

RESULTS30 out of the 208 cases (14.4%) were AMA negative patients in our study. The general status, biochemical tests and histological findings between the two groups had no significant difference (P > 0.05). The Gamma-globulin, IgG, IgM and IgA levels of AMA/AMA-M2 positive PBC patients were higher than that of the AMA negative cases (P < 0.05). The abnormal rate of cholesterol in AMA negative PBC patients was 65.4% as compared to 50.4% in AMA/AMA-M2 positive cases, no significant difference existed between (P > 0.05). Anti-nuclear antibody (ANA) was observed in 29 (96.7%) AMA negative PBC patients, including 14 (48.3%) with granular pattern, 8 (27.6%) with nuclear membrane pattern, 6 (20.7%) with kinetochore pattern and 1 (3.4%) with homogeneous pattern. AMA negative PBC patients had elevated serum ALP, GGT, IgM and cholesterol levels, and decreased serum AST, IgG and IgA levels as compared with that of autoimmune hepatitis patients (P < 0.05, respectively).

CONCLUSIONIn cholestatic patients with elevated IgM and cholesterol levels, ANA positive with non-homogeneous pattern, the diagnosis of PBC should be suspected, albeit AMA negative. The clinical, biochemical and histological features of the AMA negative PBC patients were similar to classic PBC patients, but quite different from autoimmune hepatitis.

Adult ; Antibodies, Antinuclear ; analysis ; Female ; Humans ; Liver Cirrhosis, Biliary ; immunology ; pathology ; Male ; Middle Aged ; Mitochondria ; immunology ; gamma-Globulins ; metabolism

Adult ; Aged ; CD4-Positive T-Lymphocytes ; Case-Control Studies ; Female ; Humans ; Interleukin-17 ; blood ; Liver Cirrhosis, Biliary ; blood ; immunology ; metabolism ; Male ; Middle Aged ; T-Lymphocytes, Helper-Inducer

OBJECTIVETo evaluate the sensitivity and the specificity of Anti-M2-3E ELISA for the detection of IgG- and IgA-specific isotypes of antimitochondrial antibody (AMA), and to investigate the significance of antimitochondrial IgA and IgG in the diagnosis of primary biliary cirrhosis (PBC).

METHODSSera were collected from 107 PBC patients, 87 disease controls and 26 healthy controls, and the antimitochondrial antibodies (IgG and IgA) were detected using indirect immunofluorescence (IFL), Anti-PDC ELISA and Anti-M2-3E ELISA.

RESULTSThe AMA IgG positive rate in PBC patients was 90.6% detected by Anti-M2-3E ELISA, which is significantly higher than that (81.3%) detected by IFL(t = 4.32, P < 0.05) and that (72.9%) detected by Anti- PDC ELISA (t = 6.03, P < 0.05). The AMA IgA was positive in 59 of the 107 PBC patients, and 99 of the 107 patients were positive for AMA IgG or/and IgA. 9 of the 20 IFL-negative patients were positive for AMA IgG as indicated by Anti-M2-3E ELISA, 11 of the 20 IFL-negative patients were positive for AMA IgG or/and IgA as indicated Anti-M2-3E ELISA. Compared to patients negative for IgG AMA, patients positive for IgG AMA had more severe histopathology and higher levels of ALP, IgG, and IgM.

CONCLUSIONThe IgG and IgA Anti- M2-3E ELISAs are more sensitive for the AMA detection than IFN and the Anti-PDC ELISA. The presence of AMA IgG is the characteristics of severe PBC.

Adult ; Aged ; Autoantibodies ; blood ; Biomarkers ; blood ; Biopsy, Needle ; Enzyme-Linked Immunosorbent Assay ; methods ; Female ; Fluorescent Antibody Technique, Indirect ; Hepatitis, Autoimmune ; blood ; diagnosis ; immunology ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin G ; blood ; Liver Cirrhosis, Biliary ; blood ; diagnosis ; immunology ; Liver Function Tests ; Male ; Middle Aged ; Mitochondria, Liver ; immunology ; Sensitivity and Specificity

OBJECTIVETo summarize the clinical features, diagnosis and treatment of patients with primary biliary cirrhosis (PBC) in China.

METHODSSystematic analysis of clinical characteristics by searching the Chinese literatures.

RESULTSFrom 1955 to 2007, 2740 PBC patients were reported in 103 papers (duplicated reports were deleted). The detailed information of 985 patients from 16 papers were collected. Female : male was 6.82:1. The age range was 42 to 56.2-year-old. The time from onset to diagnosis was 12 to 98.4 months. The most common symptoms were fatigue (72.40%), jaundice (67.41%), anorexia (68.58%) and pruritus (45.60%). 20% patients were asymptomatic at onset. The most frequent physical signs were splenomegaly (57.53%), hepatomegaly (43.56%) and ascites (18.45%). Serum alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) levels were markedly elevated in most of these patients. The immunological marks of AMA and M2 were positive in 88.98% and 82.65% patients, respectively. The most common comorbidity were Sjögren syndrome (9.14%), rheumatoid arthritis (3.95%) and diabetes type II (2.54%). Of the 507 patients treated with ursodeoxycholic acid (UDCA), 345 patients got complete or partial clinical biochemical response. The common complications were gastrointestinal bleeding (41.67%) and liver failure (41.67%). Liver transplantation was the only effective way for the treatment of the end-stage liver disease.

CONCLUSIONThe clinical feature of primary biliary cirrhosis in China was similar to the overseas literatures. Further research should focus on epidemic investigation, early diagnosis, long term follow up of asymptomatic patients, immunological mechanism and the efficacy of liver transplantation.

Adult ; Alanine Transaminase ; blood ; Autoantibodies ; analysis ; Biomarkers ; blood ; China ; epidemiology ; Female ; Humans ; Immunoglobulin M ; blood ; Liver Cirrhosis, Biliary ; diagnosis ; epidemiology ; immunology ; therapy ; Liver Function Tests ; Liver Transplantation ; Male ; Middle Aged ; Mitochondria, Liver ; immunology ; Retrospective Studies ; Ursodeoxycholic Acid ; therapeutic use ; gamma-Glutamyltransferase ; blood