Clinical Management of Primary Biliary Cholangitis-Strategies and Evolving Trends.

PBC is a chronic progressive autoimmune disorder involving the destruction of intrahepatic small bile ducts, cholestasis, fibrosis, and ultimately cirrhosis if left untreated. It is largely driven by the autoimmune response, but bile acids and the intestinal microbiota are implicated in disease progression as well. The only drugs licensed for PBC are UDCA and OCA. UDCA as a first-line and OCA as a second-line therapy are safe and effective, but the lack of response in a significant portion of patients and inadequate control of symptoms such as fatigue and pruritus remain as concerns. Liver transplantation is an end-stage therapy for many patients refractory to UDCA, which gives excellent survival rates but also moderate to high recurrence rates. The limited options for FDA-approved PBC therapies necessitate the development of alternative approaches. Currently, a wide variety of experimental drugs exist targeting immunological and physiological aspects of PBC to suppress inflammation. Immunological therapies include drugs targeting immune molecules in the B cell and T cell response, and specific cytokines and chemokines implicated in inflammation. Drugs targeting bile acids are also noteworthy as bile acids can perpetuate hepatic inflammation and lead to fibrosis over time. These include FXR agonists, ASBT inhibitors, and PPAR agonists such as bezafibrate and fenofibrate. Nonetheless, many of these drugs can only delay disease progression and fail to enhance patients' quality of life. Nanomedicine shows great potential for treatment of autoimmune diseases, as it provides a new approach that focuses on tolerance induction rather than immunosuppression. Tolerogenic nanoparticles carrying immune-modifying agents can be engineered to safely and effectively target the antigen-specific immune response in autoimmune diseases. These may work well with PBC especially, given the anatomical features and immunological specificity of the disease. Nanobiological therapy is thus an area of highly promising research for future treatment of PBC.

Regional Differences in Food Allergies.

The prevalence of food allergies is increasing worldwide. To understand the regional specificities of food allergies and develop effective therapeutic interventions, extensive regional epidemiological studies are necessary. While data regarding incidence, prevalence, regional variation, and treatment in food allergies are available for western countries, such studies may not be available in many Asian countries. China accounts for almost 20% of the world's population and has a vast ethnic diversity, but large-scale meta-analyses of epidemiological studies of food allergy in China are lacking. A literature search revealed 22 publications on the prevalence of food allergy in Chinese populations. A review of these studies showed that the prevalence of food allergies in China is comparable to that in western countries, even though the Chinese diet is vastly different from that of the West and may vary even greatly within China, and finally, specific antigenic triggers of food allergy vary between China and the West and also within China. Current clinical management of food allergy in China includes allergen-specific immunotherapy, Chinese herbal medicine, acupuncture, and Western medicine. This study demonstrates an unmet need in China for a thorough investigation of the prevalence of food allergies in China, the specific foods involved, and characterization of the specific antigenic triggers of food allergy with respect to ethnicity, age, and diet in China.

Microbiota and Food Allergy.

Emerging evidence suggests that the increasing prevalence of food allergies is associated with compositional and functional changes in our gut microbiota. Microbiota-host interactions play a key role in regulating the immune system. Development of a healthy gut microbiota and immune system occurs early in life and is largely shaped by exposure to maternal microbes through vaginal/natural delivery and breast milk, whereas use of antibiotics can disrupt gut homeostasis and significantly raise the risk of allergic diseases. Thus, changes in the quantity or diversity of gut microbes affect oral toleranace through interations of microbial molecules with pattern recognition receptors on immune cells and confer susceptibility to food allergies. On the other hand, short chain fatty acids which are fermentation end products of insoluble fibers by intestinal micoorganisms have been shown to confer protective effects on food allergy. As a preventive and therapeutic treatment for food allergies, probiotics have gained widespread attention in recent years. Reintroducing certain commensal microbes, such as Clostridia, both in animal models and clinical trials led to the prevention or resolution of allergic symptoms. This review highlights recent progress in our understanding of the gut microbiota's role in food allergy. However, mechanistic details underlying the anti-allergic effects of probiotics and the interaction between the gut microbiota and the immune system remain circumstantial and are not fully understood. Future studies should address possible factors and underlying mechanisms for microbiota-host interactions and gut immunity, as well as the efficacy, safety, and appropriate use of probiotics in establishing a standard treatment regimen for food allergies.

A contemporary perspective on the molecular characteristics of mitochondrial autoantigens and diagnosis in primary biliary cholangitis.

Primary biliary cholangitis (PBC) is an autoimmune hepatobiliary disease characterized by immune mediated destruction of the intrahepatic small bile ducts and the presence of antimitochondrial antibodies (AMAs). The mitochondrial autoantigens have been identified as the E2 subunits of the 2-oxo-acid dehydrogenase complex, including the E2 subunits of pyruvate dehydrogenase, branched-chain 2-oxo acid dehydrogenase complex, oxoglutarate dehydrogenase complex, E3 binding protein and PDC E1 alpha subunit. The AMA epitope is mapped within the E2 lipoic acid binding domain, which is particularly important for oxidative phosphorylation. In addition, lipoic acid, which serves as a swinging arm to capture electrons, is particularly susceptible to an electrophilic attack and may provide clues to the etiology of PBC. This review emphasizes the molecular characteristics of AMAs, including detection, immunochemistry and the putative role in disease. These data have significance not only specifically for PBC, but generically for autoimmunity.