The Role of Invariant NKT in Autoimmune Liver Disease: Can Vitamin D Act as an Immunomodulator?

Natural killer T (NKT) cells are a distinct lineage of T cells which express both the T cell receptor (TCR) and natural killer (NK) cell markers. Invariant NKT (iNKT) cells bear an invariant TCR and recognize a small variety of glycolipid antigens presented by CD1d (nonclassical MHC-I). CD1d-restricted iNKT cells are regulators of immune responses and produce cytokines that may be proinflammatory (such as interferon-gamma (IFN-)) or anti-inflammatory (such as IL-4).

Delayed rupture of a vertebral artery laceration: a case report and challenges for the forensic pathologist.

Vertebral artery laceration/dissection (VALD) resulting in fatal subarachnoid hemorrhage (SAH) is a rare, but well-known phenomenon encountered in the forensic setting. Delayed ruptures are exceptionally rare, and pose several challenges to the forensic pathologist. In this paper we present a case of a 47-year-old male who collapsed suddenly following recent complaints of a headache and a reported seizure.

Diagnostic and clinical significance of Crohn's disease-specific pancreatic anti-GP2 and anti-CUZD1 antibodies.

Background: Pancreatic autoantibodies (PAB) targeting GP2 and CUZD1 are Crohn's disease (CrD)-markers. The clinical significance of anti-GP2 antibodies has been assessed, but that of anti-CUZD1 remains elusive. The aim of the study was to assess the clinical utility of anti-CUZD1/anti-GP2 by novel cell-based indirect immunofluorescence (IIF) assays in CrD.

E. coli Induced Experimental Model of Primary Biliary Cirrhosis: At Last.

Recurrent urinary tract infections (UTI) have been considered potential triggers of primary biliary cirrhosis (PBC), an autoimmune cholestatic liver disease characterised by progressive destruction of intrahepatic bile ducts. Additional support for the link made between PBC and UTI was based on early observations of recurrent episodes of bacteriuria in female patients with PBC. A series of large epidemiological studies demonstrated a strong correlation between recurrent UTI and PBC, initiating a series of studies investigating the role of Escherichia coli (E.

Diagnostic and clinical significance of Crohn's disease-specific anti-MZGP2 pancreatic antibodies by a novel ELISA.

Background: We developed a new IgA and IgG anti-MZGP2 antibody ELISAs based on recombinant isoform-4 of human zymogen granule protein-2 (GP2), which is the major autoantigen of Crohn's disease (CrD)-specific pancreatic autoantibodies and assessed their clinical relevance in the largest inflammatory bowel disease (IBD) cohort tested to date.

Methods: 832 sera were studied, including 617 consecutive IBD patients from 323 CrD and 294 ulcerative colitis (UC) follow-up in a tertiary centre, and 112 pathological and 103 normal controls.

Results: Sensitivity of IgA anti-MZGP2 for CrD in the IBD population was 15% and specificity was 98% (95, 99), while the sensitivity and specificity of IgG anti-MZGP2 were 27% and 97%.

Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn's disease.

Background: A link between measles virus and Crohn's disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry.

Methods: The BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins.

Low serum vitamin D levels are associated with severe histological features and poor response to therapy in patients with autoimmune hepatitis.

Background And Aim: 25-Hydroxyvitamin D [25(OH)D] has an important role in fibrosis progression and inflammatory response in patients with various etiologies of chronic liver disease. However, its influence on autoimmune hepatitis (AIH) has not been investigated. We evaluated the association of serum 25(OH)D levels with clinical, biochemical and histological features and response to therapy in AIH.

Acute disseminated encephalomyelitis progressing to multiple sclerosis: are infectious triggers involved?

Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are demyelinating disorders affecting the central nervous system. An autoimmune aetiology has been proposed for both. ADEM principally affects adolescents following acute infection by a variety of pathogens and has also been reported to occur following vaccination.

Helicobacter pylori and autoimmune disease: cause or bystander.

Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis.

Primary biliary cirrhosis-specific antimitochondrial antibodies in neonatal haemochromatosis.

Background And Aim: Neonatal hemochromatosis (NH) is characterised by severe liver injury and extrahepatic siderosis sparing the reticuloendothelial system. Its aetiology is obscure, although it has been proposed as an alloimmune disease, resulting from immunological reaction to self-antigens (alloantigens) which the body recognizes as foreign. We studied an infant with NH and his mother whose sera contained antimitochondrial antibody (AMA), the hallmark of primary biliary cirrhosis (PBC).

p38 MAPK Signaling in Pemphigus: Implications for Skin Autoimmunity.

p38 mitogen activated protein kinase (p38 MAPK) signaling plays a major role in the modulation of immune-mediated inflammatory responses and therefore has been linked with several autoimmune diseases. The extent of the involvement of p38 MAPK in the pathogenesis of autoimmune blistering diseases has started to emerge, but whether it pays a critical role is a matter of debate. The activity of p38 MAPK has been studied in great detail during the loss of keratinocyte cell-cell adhesions and the development of pemphigus vulgaris (PV) and pemphigus foliaceus (PF).

Vitamin D in autoimmune liver disease.

The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties.

TRAF1-C5 affects quality of life in patients with primary biliary cirrhosis.

Background: Previous studies reported associations between specific alleles of non-HLA immunoregulatory genes and higher fatigue scores in patients with primary biliary cirrhosis (PBC).

Aim: To study the relationship between variables of health-related quality of life (HRQoL) and single nucleotide polymorphisms of TRAF1-C5, a member of the tumor necrosis factor receptor family.

Patients And Methods: TRAF1-C5 gene polymorphisms, rs2900180 and rs3761847, were analysed in 120 Caucasian PBCs.

Tracing environmental markers of autoimmunity: introducing the infectome.

We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of adaptive mechanisms in the body. These studies complement genome-wide association studies, which establish the genetic predisposition to disease.

Infectome: a platform to trace infectious triggers of autoimmunity.

The "exposome" is a term recently used to describe all environmental factors, both exogenous and endogenous, which we are exposed to in a lifetime. It represents an important tool in the study of autoimmunity, complementing classical immunological research tools and cutting-edge genome wide association studies (GWAS). Recently, environmental wide association studies (EWAS) investigated the effect of environment in the development of diseases.

Tuberculosis is not a risk factor for primary biliary cirrhosis: a review of the literature.

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterised serologically by cholestasis and the presence of high-titre antimitochondrial antibodies, and histologically by chronic nonsuppurative cholangitis and granulomata. As PBC is a granulomatous disease and Mycobacterium tuberculosis is the most frequent cause of granulomata, a causal relation between tuberculosis and PBC has been suggested. Attempts to find serological evidence of PBC-specific autoantibodies such as AMA have been made and, conversely, granulomatous livers from patients with PBC have been investigated for molecular evidence of Mycobacterium tuberculosis.

p38 mitogen-activated protein kinase (p38 MAPK)-mediated autoimmunity: lessons to learn from ANCA vasculitis and pemphigus vulgaris.

Evidence is beginning to accumulate that p38 mitogen activated protein kinase (p38 MAPK) signaling pathway plays an important role in the regulation of cellular and humoral autoimmune responses. The exact mechanisms and the degree by which the p38 MAPK pathway participates in the immune-mediated induction of diseases have started to emerge. This review discusses the recent advances in the molecular dissection of the p38 MAPK pathway and the findings generated by reports investigating its role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and autoimmune hepatitis.

Potential Roles for Infectious Agents in the Pathophysiology of Primary Biliary Cirrhosis: What's New?

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease serologically characterized by the presence of high-titer antimitochondrial antibodies and, histologically by chronic nonsuppurative cholangitis and granulomata. The aetiology of the disease remains elusive, although genetic, epigenetic, environmental, and infectious factors have been considered important for the induction of the disease in genetically prone individuals. The disease shows a striking female predominance and becomes clinically overt at the fourth to sixth decade.

Rheumatoid arthritis and primary biliary cirrhosis: cause, consequence, or coincidence?

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease characterized serologically by cholestasis and the presence of high-titre antimitochondrial antibodies and histologically by chronic nonsuppurative cholangitis and granulomata. PBC patients often have concomitant autoimmune diseases, including arthropathies. This raises the question as to whether there are shared features in the pathogenesis of those diseases with the pathogenesis of PBC.

Ileal inflammation may trigger the development of GP2-specific pancreatic autoantibodies in patients with Crohn's disease.

Why zymogen glycoprotein 2 (GP2), the Crohn's disease (CD)-specific pancreatic autoantigen, is the major target of humoral autoimmunity in inflammatory bowel diseases (IBD) is uknown. Recent evidence demonstrates that GP2 is also present on the apical surface of microfold (M) intestinal cells. As the colon lacks GP2-rich M cells, we assumed that patients with colonic CD are seronegative for anti-GP2.

Autoantibodies in autoimmune pancreatitis.

Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA.

Autoimmune hepatitis type 2 associated with an unexpected and transient presence of primary biliary cirrhosis-specific antimitochondrial antibodies: a case study and review of the literature.

Background: Unlike other autoimmune liver diseases, primary biliary cirrhosis (PBC) has never been reported in early childhood, while type 2 autoimmune hepatitis (AIH) is eminently a paediatric disease.

Case Presentation: We describe a case of type 2 AIH with serological positivity for PBC-specific anti-mitochondrial antibodies (AMA) in a 3-year old girl. We found this observation intriguing as AMA and indeed an overlap with PBC are virtually absent in Type 2 AIH, a pediatric form of AIH which is distinct precisely because it is characterized by pathognomonic anti-liver kidney microsomal type 1 (LKM-1) showing a remarkable antigen-specificity directed against cytochrome P4502D6.

Sex differences associated with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a cholestatic liver disease of autoimmune origin, characterised by the destruction of small intrahepatic bile ducts. The disease has an unpredictable clinical course but may progress to fibrosis and cirrhosis. The diagnostic hallmark of PBC is the presence of disease-specific antimitochondrial antibodies (AMA), which are pathognomonic for the development of PBC.

Epstein-barr virus as a trigger of autoimmune liver diseases.

The pathogenesis of autoimmune diseases includes a combination of genetic factors and environmental exposures including infectious agents. Infectious triggers are commonly indicated as being involved in the induction of autoimmune disease, with Epstein-Barr virus (EBV) being implicated in several autoimmune disorders. EBV is appealing in the pathogenesis of autoimmune disease, due to its high prevalence worldwide, its persistency throughout life in the host's B lymphocytes, and its ability to alter the host's immune response and to inhibit apoptosis.