Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic progressive autoimmune cholestatic disease. The main target organ of PBC is the liver, and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis. AIM: To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC. METHODS: The data of 82 patients with PBC confirmed by pathology at Tianjin Second People's Hospital from January 2013 to November 2021 were collected, and the patients were divided into stage I, stage II, stage III, and stage IV according to the pathological stage. The general data, serum biochemistry, immunoglobulins, and autoimmune antibodies of patients in each stage were retrospectively analyzed. RESULTS: In early-stage (stages I + II) PBC patients, 50.0% of patients had normal alanine aminotransferase (ALT) levels, and 37.5% had normal aspartate aminotransferase (AST) levels. For the remaining patients, the ALT and AST levels were mildly elevated; all of these patients had levels of < 3 times the upper limit of normal values. The AST levels were significantly different among the three groups (stages I + II vs stage III vs stage IV, P < 0.05). In the early stage, 29.2% of patients had normal alkaline phosphatase (ALP) levels. The remaining patients had different degrees of ALP elevation; 6.3% had ALP levels > 5 times the upper limit of normal value. Moreover, γ-glutamyl transferase (GGT) was more robustly elevated, as 29.2% of patients had GGT levels of > 10 times the upper limit of normal value. The ALP values among the three groups were significantly different (P < 0.05). In early stage, the jaundice index did not increase significantly, but it gradually increased with disease progression. However, the above indicators were significantly different (P < 0.05) between the early-stage group and the stage IV group. With the progression of the disease, the levels of albumin and albumin/globulin ratio tended to decrease, and the difference among the three groups was statistically significant (P < 0.05). In early-stage patients, IgM and IgG levels as well as cholesterol levels were mildly elevated, but there were no significant differences among the three groups. Triglyceride levels were normal in the early-stage group, and the differences among the three groups were statistically significant (P < 0.05). The early detection rates of anti-mitochondria antibody (AMA) and AMA-M2 were 66.7% and 45.8%, respectively. The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC. When AMA and AMA-M2 were negative, in the early stage, the highest autoantibody was anti-nuclear antibody (ANA) (92.3%), and in all ANA patterns, the highest was ANA centromere (38.5%). CONCLUSION: In early-stage PBC patients, ALT and AST levels are normal or mildly elevated, GGT and ALP levels are not elevated in parallel, GGT levels are more robustly elevated, and ALP levels are normal in some patients. When AMA and AMA-M2 are negative, ANA especially ANA centromere positivity suggests the possibility of early PBC. Therefore, in the clinic, significantly elevated GGT levels with or without normal ALP levels and with ANA (particularly ANA centromere) positivity (when AMA and AMA-M2 are negative) may indicate the possibility of early PBC.

Prediction of pre-eclampsia combining NGAL and other biochemical markers with Doppler in the first and/or second trimester of pregnancy. A pilot study.

OBJECTIVE: To determine the performance of maternal characteristics, Doppler and a set of biochemical markers for pre-eclampsia (PE) screening at 11+0 to 13+6 and 20+1 to 25+6 weeks' gestation. STUDY DESIGN: Prospectively enrolled women at 11+0 to 13+6 and 20+1 to 25+6 weeks. Maternal characteristics, uterine artery pulsatility index (UtA-PI), ductus venosus pulsatility index (DV-PI) and serum biomarkers including pregnancy associated plasma protein - A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), s-Flt-1/PLGF ratio, asymmetric dimethylarginine (ADMA), matrix metalloproteinase 9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex were recorded. RESULTS: Combination of NGAL and BMI in a logistic regression model detected 70% of PE in the first trimester (p=0.001). Including UtA-PI and DV-PI in the model sensitivity reached 77.8% with 96.6% specificity (p=0.004). Combination of second trimester NGAL and s-Flt-1/PLGF ratio yield specificity 100% (p=0.001). Combination of second trimester UtA-PI with first trimester NGAL, BMI and age detected 80% of PE with specificity 91.9% (p=0.001). CONCLUSION: Combination of NGAL, maternal characteristics and Doppler parameters in the first and/or second trimester can detect a consistent number of PE pregnancies. NGAL is a potent new biomarker for the prediction of preeclampsia.

Mesenchymal stem cells in autism spectrum and neurodevelopmental disorders: pitfalls and potential promises.

OBJECTIVES: In this conceptual review, the authors discuss the promises and pitfalls in the use of mesenchymal stem cells as a potential experimental therapeutic for autism spectrum and other neurodevelopmental disorders. METHODS: The relevant literature in autism spectrum disorders and other neurodevelopmental disorders regarding immune dysregulation and neuroinflammation and relevant therapeutics with mesenchymal stem cell infusion is reviewed. The relevant literature pertaining to mesenchymal stem cells and their clinical applications is also reviewed. RESULTS: It is proposed that immune dysregulation and neuroinflammation play a role in the aetiology of autism spectrum disorders. Mesenchymal stem cells have been shown to have immune-modulating capabilities and are neuroprotective. There are three international studies that have utilized mesenchymal stem cell infusions as a treatment for children with autism spectrum disorders, all of which demonstrated improvement in autism rating scale scores, although each study has limitations which are described. CONCLUSIONS: Mesenchymal stem cell transplantation for the treatment of autism spectrum disorders is a novel approach that deserves further investigation, however substantial methodological and theoretical challenges and pitfalls remain before this can be considered a viable therapeutic option.