Preventive but Not Therapeutic Topical Application of Local Anesthetics Can Inhibit Experimental Epidermolysis Bullosa Acquisita in Mice.

Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disorder characterized and caused by autoantibodies against type VII collagen (COL7). Although it has been noticed that EBA in both patients and mice is associated with an increased scratching, it is not clear whether and how the scratching contributes to disease manifestation. Hence, we here aimed to validate this clinical observation and also to investigate the potential contribution of increased scratching in EBA pathogenesis in mice.

Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers.

Background: Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation, obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, eg, cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking.

Gene Expression Profiling of Lacrimal Glands Identifies the Ectopic Expression of MHC II on Glandular Cells as a Presymptomatic Feature in a Mouse Model of Primary Sjögren's Syndrome.

Ectopic expression of MHC II molecules on glandular cells is a feature of primary Sjögren's syndrome (pSS). However, the cause of this ectopic expression and its potential role in the pathogenesis of the disease remains elusive. Here, we report that ectopic expression of MHC II molecules on glandular cells represents an early presymptomatic event in a mouse model of pSS induced by immunization of Ro60_316-335 peptide emulsified in TiterMax® as an adjuvant.

Neutrophil Adhesion Is a Prerequisite for Antibody-Mediated Proteolytic Tissue Damage in Experimental Models of Epidermolysis Bullosa Acquisita.

Although uncontrolled proteolytic activity mediated by activated neutrophils is a major reason for tissue damage, therapeutic approaches using protease inhibitors are inefficient. Here, we investigated the role of the immune complex-induced neutrophil adhesion and protease release in tissue damage. We show both in vitro and in vivo that immune complex-mediated neutrophil adhesion to the target tissue depends on β integrins.

B Cells Are Indispensable for a Novel Mouse Model of Primary Sjögren's Syndrome.

Primary Sjögren's syndrome (pSS) is characterized by a panel of autoantibodies, while it is not clear whether B cells and autoantibodies play an essential role in pathogenesis of the disease. Here, we report a novel mouse model for pSS which is induced by immunization with the Ro60_316-335 peptide containing a predominant T cell epitope. After immunization, mice developed several symptoms mimicking pSS, including a decreased secretion of tears, lymphocytic infiltration into the lacrimal glands, autoantibodies, and increased levels of inflammatory cytokines.

Detection of Apolipoprotein E Gene Polymorphism and Blood Lipid Level in Hemodialysis Patients.

Background: The aim was to investigate the clinical characteristics of lipid metabolism and the effect of apolipoprotein E (ApoE) gene polymorphism on lipid metabolism in hemodialysis patients.

Methods: The serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), ApoA1, ApoB, ApoE and lipoprotein Lp(a) were detected by polymerase chain reaction-restriction fragment length (PCR-RFLP).

Results: The level of serum TG was significantly increased and the level of HDLC was significantly decreased in hemodialysis patients.

Ectodysplasin A protein promotes corneal epithelial cell proliferation.

The gene encodes ectodysplasin A (Eda), which if mutated causes X-linked hypohidrotic ectodermal dysplasia (XLHED) disease in humans. Ocular surface changes occur in XLHED patients whereas its underlying mechanism remains elusive. In this study, we found Eda was highly expressed in meibomian glands, and it was detected in human tears but not serum.

Myeloid-related proteins-8 and -14 are expressed but dispensable in the pathogenesis of experimental epidermolysis bullosa acquisita and bullous pemphigoid.

Background: Myeloid-related protein-8 (MRP-8) and its heterodimeric partner, MRP-14 belong to the group of danger-associated molecular patterns (DAMPs) and are associated with numerous chronic human disorders. However, their functional role in autoimmunity remains largely unclear.

Objective: Here, we examined the involvement of MRP-8/-14 in two difficult-to-treat autoimmune blistering diseases, epidermolysis bullosa acquisita (EBA) and bullous pemphigoid (BP).

Revisiting the role of mast cells in autoimmunity.

Beside their well known role in allergy, mast cells (MCs) are capable to sense multiple signals and have therefore the potential to be involved in many immune responses. MCs are actively present in the target tissues of some autoimmune disorders, suggesting a possible function in the manifestation of such diseases. This idea is strengthened by the evidence that KIT-dependent MC-deficient mice are protected from disease in many mouse models of autoimmunity, including multiple sclerosis, rheumatoid arthritis and autoimmune skin blistering diseases.

The amino acid variation within the binding pocket 7 and 9 of HLA-DRB1 molecules are associated with primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is associated with HLA-DRB1 loci, but the association of amino acid variations in the hypervariable region of the HLA-DR β1 chain with pSS is largely unknown. In this study, we aimed to identify the amino acid variations within the hypervariable region of HLA-DRB1 molecule which are associated with the susceptibility to pSS. We sequenced the 2nd exon of the HLA-DRB1 locus in 52 pSS patients and 179 controls.

mtDNA sequence, phylogeny and evolution of laboratory mice.

Laboratory mice are important tools for biomedical research. Aiming to investigate the phylogeny and evolution of laboratory mice, we investigated the mtDNA sequences of classic inbred strains, classic outbred stocks and wild-derived inbred strains. Our results showed that the most classic outbred stocks and classic inbred strains are descended from a single mtDNA ancestor.

EndoS reduces the pathogenicity of anti-mCOL7 IgG through reduced binding of immune complexes to neutrophils.

Endo-β-N-acetylglucosaminidase (EndoS) has been shown to act as a potent pathogen-derived immunomodulatory molecule in autoimmune diseases. Here we investigated how EndoS treatment reduces the pathogenicity of rabbit anti-mCOL7 IgG using different experimental models of epidermolysis bullosa acquisita (EBA). Our results show that the EndoS treatment does not interfere with the binding of the antibody to the antigen but reduces immune complex (IC)-mediated neutrophil activation by impairing the binding of the IC to FcγR on neutrophils.

The role of PTPN22 in autoimmunity: learning from mice.

Protein tyrosine phosphatase nonreceptor 22 (PTPN22) represents a strong susceptibility gene which is shared by many autoimmune diseases. Exploring the mechanism behind this association could help to understand their pathogenesis as well as to identify novel therapeutical targets. Recently, multiple mouse models including knock-out, knock-in, knock-down and transgenic mice were generated to delineate PTPN22s function in this context.

Meta-analysis reveals an association of STAT4 polymorphisms with systemic autoimmune disorders and anti-dsDNA antibody.

Signal transducer and activator of transcription 4 (STAT4) has been recently identified as a susceptibility gene for multiple autoimmune diseases. Here we performed a comprehensive analysis of the association between STAT4 and several different autoimmune disorders to identify potential common inflammatory principles behind this association. Our meta-analysis revealed that the STAT4 rs7574865 polymorphism is associated with four autoimmune diseases with systemic pathology, including systemic lupus erythematosus (OR = 1.

Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases.

Analytical and clinical evaluation of CYFRA 21-1 by electrochemiluminescent immunoassay in head and neck squamous cell carcinoma.

This paper attempts to evaluate the clinical usefulness of CYFRA 21-1 as a serum tumour marker in patients with head and neck squamous cell carcinoma (HNSCC). The serum concentration of CYFRA 21-1 was measured utilizing a new electrochemiluminescent immunoassay (ECLIA) in 142 patients with HNSCC before and after treatment, 68 patients with benign tumours of the head and neck, and 50 healthy controls. Serum levels of CYFRA 21-1 in patients with HNSCC were significantly higher than those of benign tumours and healthy controls (p < 0.