Autoimmune liver serology: Current diagnostic and clinical challenges

Abstract

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and nonspecific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation

“…22 Antibody Production in S.i.-Inoculated Mice Sera were obtained from S.i.-inoculated BALB/c mice to study antibody production. HEp-2 23 and HuCCT1 cells were seeded onto glass-bottom dishes (MATSUNAMI), fixed with 95% ethanol, and blocked with 3% nonfat milk containing 2% Triton X-100 in PBS. The cells were then stained using a 1:100 dilution of each mouse serum in PBS followed by incubation with FITC-conjugated anti-mouse IgG (Jackson ImmunoResearch).…”

The Prevalence of Autoantibodies in Patients with Chronic Hepatitis C and the Relationship between Autoantibodies and HCV RNA Positivity

“…Böylece çalışmamızda incelenen otoantikorlardan sadece AMA pozitifliğinin HCV RNA pozitifliği ile direk bir ilişkisinin olduğu tespit edilmiştir. AMA, otoimmün hepatitlerden olan primer biliyer sirozda sık rastlanan ve hastalığın tanısında önemli bir serolojik belirteç olan bir otoantikordur (4) . AMA otoantikorunun HCV RNA pozitif yani viral replikasyon gösteren hasta örneklerinde daha sık olarak bulunması, HCV'nin bu otoantikorun oluşumundan sorumlu bir faktör olabileceğini düşündürmektedir.…”

Hepatitis Autoinmune en niños en un Hospital de Tercer Nivel. Reporte de casos

“…En los estudios de laboratorio, es más frecuente e n c o n t r a r e l e va c i ó n d e t r a n s a m i n a s a s e (10)(11)(12) hipergammaglobulinemia .…”