Role of autoantibodies in the clinical management of primary biliary cholangitis

Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by immune-driven destruction of small intrahepatic bile ducts leading a proportion of patients to hepatic failure over the years.Diagnosis at early stages in concert with ursodeoxycholic acid treatment has been linked with prevention of disease progression in the majority of cases.Diagnosis of PBC in a patient with cholestasis relies on the detection of disease-specific autoantibodies,including anti-mitochondrial antibodies,and disease-specific anti-nuclear antibodies targeting sp100 and gp210.These autoantibodies assist the diagnosis of the disease,and are amongst few autoantibodies the presence of which is included in the diagnostic criteria of the disease.They have also become important tools evaluating disease prognosis.Herein,we summarize existing data on detection of PBC-related autoantibodies and their clinical significance.Moreover,we provide insight on novel autoantibodies and their possible prognostic role in PBC patients.

B cell depletion in treating primary biliary cirrhosis:Pros and cons

Primary biliary cirrhosis (PBC) is a progressive autoim- mune liver disease of unknown etiology that affects almost exclusively women.Ursodeoxycholic acid (UDCA) is currently the only approved drug by Food and Drug Administration for patients with PBC.Although the precise pathogenesis of PBC remains unclear,it has been postulated that many cell populations,including B cells,are involved in the ongoing inflammatory process,which implicates,not surprisingly,a potential thera- peutic target of depleting B cell to treat this disorder.Rituximab is a chimeric anti-CD20 monoclonal antibody that has been approved for the treatment of lymphoma and some autoimmune diseases such as rheumatoid arthritis.Whether it is effective in the treatment of PBC has not been evaluated.Recently,Tsuda et al [1] demon- strated that B cell depletion with rituximab significantly reduced the number of anti-mitochondrial antibodies (AMA)-producing B cells,AMA titers,the plasma levels of immunoglobulins (IgA,IgM and IgG) as well as se- rum alkaline phosphatase,and it was well tolerated by all the treated patients with no serious adverse events.This observation provides a novel treatment option for the patients with PBC who have incomplete response to UDCA.

From infections to autoimmunity:Diagnostic challenges in common variable immunodeficiency

Common variable immunodeficiency(CVID)is the most common clinically significant primary antibody deficiency diagnosed in adults.The early symptoms are not specific.They include common infections,mainly of the respiratory tract,caused by typical microorganisms,so cases can be missed in primary care.In the majority of patients increased susceptibility to infections coexists with signs or symptoms of autoimmunity,inflammation or polyclonal lymphoproliferation,which can divert diagnosis from immune deficiency.The overall incidence of malignancy is increased in CVID and certain cancers are significantly more common.Lymphomas and gastric carcinoma are the most frequently reported malignancies in CVID,so a high index of suspicion is recommended.Diagnostic delay in CVID is seen worldwide.The main goal of this paper is to increase the awareness about CVID among health care professionals.We aim to present features which can be helpful in CVID diagnosis in order to shorten the“latency”of proper management of CVID patients.We review clinical symptoms,complications and laboratory abnormalities of CVID.Immunoglobulin replacement therapy is regarded as the cornerstone of pharmacological intervention.New modes of Ig application,mainly subcutaneously and via the hyaluronidase-facilitated subcutaneous route,help to adjust therapy to patients’needs and preferences.Still there remain unmet needs.It remains to be seen whether CVID complications can be avoided by earlier diagnosis,treatment and thorough monitoring in the context of increased risk of malignancy.Development of patient tailored protocols depending on the clinical phenotype and risk factors might be more appropriate.The most important consideration is to diagnose suspected cases and stratify patients in a precise and timely way.Work is needed to define features predictive of unfavorable prognosis.