shRNA-Targeting Caspase-3 Inhibits Cell Detachment Induced by Pemphigus Vulgaris Autoantibodies in Cells.

Pemphigus is an autoimmune disease that affects the skin and mucous membranes, induced by the deposition of pemphigus IgG, which mainly targets desmogleins 1 and 3 (Dsg1 and 3). This autoantibody causes steric interference between Dsg1 and 3 and the loss of cell adhesion, producing acantholysis. This molecule and its cellular effects are clinically reflected as intraepidermal blistering.

suPAR and WT1 modify the adhesion of podocytes and are related to proteinuria in class IV lupus nephritis.

Introduction: Lupus nephritis (LN) affects up to 60 % of the patients with Systemic Lupus Erythematosus (SLE) and renal damage progression is associated with proteinuria, caused in part by the integrity of the glomerular basement membrane (GBM) and by podocyte injury. The soluble urokinase plasminogen activator receptor (suPAR) and Wilms Tumor 1 (WT1) have been related to podocyte effacement and consequently with proteinuria which raises questions about its pathogenic role in LN.

Objective: Define whether suPAR levels and WT1 expression influence in podocyte anchorage destabilization in LN class IV.

Multiple autoimmunity and epitope spreading in monozygotic twins.

We report clinical, serologic, and immunogenetic studies of a set of monozygotic male twin patients who develop autoimmune thyroiditis and vitiligo associated with the HLA-DRB1*04-DQB1*03:02 and HLA-DRB1*03-DQB1*0201 haplotypes. The patients had detectable anti-thyroid and anti-melanocyte autoantibodies. A critical review is presented regarding the role of MHC II molecules linked to clinical manifestations of various autoimmune diseases displayed in a single patient, as is the case in the twin patients reported here.

Activation of Peptidylarginine Deiminase in the Salivary Glands of Mice Drives the Citrullination of Ro and La Ribonucleoproteins.

The goal of the present study was to determine whether peptidylarginine deiminase PAD2 and PAD4 enzymes are present in mouse salivary glands and whether they are able to citrullinate Ro and La ribonucleoproteins. Salivary glands from mice were cultured in DMEM and supplemented with one of the following stimulants: ATP, LPS, TNF, IFN, or IL-6. A control group without stimulant was also evaluated.

Cytoplasmic Localization of WT1 and Decrease of miRNA-16-1 in Nephrotic Syndrome.

Nephrotic syndrome (NS) is a glomerular disease that is defined by the leakage of protein into the urine and is associated with hypoalbuminemia, hyperlipidemia, and edema. Steroid-resistant NS (SRNS) patients do not respond to treatment with corticosteroids and show decreased Wilms tumor 1 (WT1) expression in podocytes. Downregulation of WT1 has been shown to be affected by certain microRNAs (miRNAs).

Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population.

Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease.

An Animal Model Using Metallic Ions to Produce Autoimmune Nephritis.

Autoimmune nephritis triggered by metallic ions was assessed in a Long-Evans rat model. The parameters evaluated included antinuclear autoantibody production, kidney damage mediated by immune complexes detected by immunofluorescence, and renal function tested by retention of nitrogen waste products and proteinuria. To accomplish our goal, the animals were treated with the following ionic metals: HgCl2, CuSO4, AgNO3, and Pb(NO3)2.

Soluble fas and the -670 polymorphism of fas in lupus nephritis.

This study was performed to clarify the role of soluble Fas (sFas) in lupus nephritis (LN) and establish a potential relationship between LN and the -670 polymorphism of Fas in 67 patients with systemic lupus erythematosus (SLE), including a subset of 24 LN patients with proteinuria. Additionally, a group of 54 healthy subjects (HS) was included. The allelic frequency of the -670 polymorphism of Fas was determined using PCR-RFLP analysis, and sFas levels were assessed by ELISA.

An Activin Receptor IA/Activin-Like Kinase-2 (R206H) Mutation in Fibrodysplasia Ossificans Progressiva.

Fibrodysplasia ossificans progressiva (FOP) is an exceptionally rare genetic disease that is characterised by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomical areas. This disease is caused by a mutation in activin receptor IA/activin-like kinase-2 (ACVR1/ALK2). A Mexican family with one member affected by FOP was studied.

Posttranslational Protein Modification in the Salivary Glands of Sjögren's Syndrome Patients.

The present study investigated posttranslational reactions in the salivary glands of patients with Sjögren's syndrome. We analysed the biopsies of primary Sjögren's patients using immunohistochemistry and a tag-purified anticyclic citrullinated protein (CCP) antibody to detect citrullinated peptides, and the presence of peptidylarginine deiminase 2 (PAD2) was assessed simultaneously. The present work demonstrated the weak presence of the PAD2 enzyme in some normal salivary glands, although PAD2 expression was increased considerably in Sjögren's patients.

Autoantibodies in senear-usher syndrome: cross-reactivity or multiple autoimmunity?

Senear-Usher syndrome or pemphigus erythematosus is a pathology that overlaps clinically and serologically with pemphigus foliaceus and lupus erythematosus. Skin biopsies of patients with pemphigus erythematosus reveal acantholysis and deposits of immunoglobulins in desmosomes, and they are positive in the lupus band test. In the present paper, we determined whether the autoantibodies associated with pemphigus erythematosus targeted a single antigen or multiple antigens as a result of the stimulation of independent B cell clones.

The caspase pathway as a possible therapeutic target in experimental pemphigus.

Apoptosis plays a role in pemphigus IgG-dependent acantholysis; theoretically, the blockade of the caspase pathway could prevent the blistering that is caused by pemphigus autoantibodies. Using this strategy, we attempted to block the pathogenic effect of pemphigus IgG in Balb/c mice by using the caspase inhibitor Ac-DEVD-CMK. This inhibitor was administrated before the injection of pemphigus IgG into neonatal mice.

Inhibitors of MAPK pathway ERK1/2 or p38 prevent the IL-1{beta}-induced up-regulation of SRP72 autoantigen in Jurkat cells.

Phosphorylation is the most important post-translational event at a cellular level that is regulated by protein kinases. MAPK is a key player in the important cellular signaling pathway. It has been hypothesized that phosphorylation might have a role in the induction of break tolerance against some autoantigens such as SRP72.

Tacrolimus therapy for circinate balanitis associated with reactive arthritis.

Background: Reactive arthritis is the current name for the clinical triad characterized by arthritis, urethritis, and conjunctivitis, which develops over the course of a month or more. In some patients, this clinical triad is accompanied by circinate balanitis and keratoderma on the palms and soles. Balanitis, in some cases, is refractory to conventional therapy and can be recurrent, becoming a therapeutic challenge.

Apoptosis and cell proliferation: the paradox of salivary glands in Sjögren's disease.

Aim: To assess apoptosis and proliferation in salivary glands of patients with primary Sjögren's syndrome.

Methods: Studies were performed in twenty four minor salivary glands from patients with primary Sjögren's syndrome and an equal number of controls. Apoptosis was studied by immunohistochemistry using monoclonal antibodies anti-Fas FasL and Caspase 3 and apoptotic features by TUNEL.

Gender as a factor of susceptibility to infection in experimental hydatidosis.

We developed an experimental model of hydatidosis in BALB/c mice with six groups, a group of females and another group of males was infected with PSC of Echinococcus, granulosus. Another two groups were gonadectomised and infected with PSC. and another two groups were healthy controls.

GW bodies: from RNA biology to clinical implications in autoimmunity.

Evaluation of: Lian S, Fritzler M, Katz J et al. Small interfering RNA-mediated silencing induces target-dependent assembly of GW/P bodies. Mol.

Production of anti-epithelial antibodies and acantholysis by vaccination with an anti-idiotypic antibody, mimicking desmoglein 1.

Theoretically, the immunization of experimental animals with an anti-idiotype antibody may elicit antibodies that recognize epitopes like the original idiotype; this is archived via internal images. Using this strategy, we attempted to produce anti-epithelial antibodies in Balb/c mice immunized with a pemphigus anti-idiotypic determinant. First, when an anti-idiotype antibody was produced in rabbits by immunization with pemphigus immunoglobulin G (IgG), the anti-idiotypic activity was tested successfully.

Apoptosis and redistribution of the Ro autoantigen in Balb/c mouse like in subacute cutaneous lupus erythematosus.

In subacute cutaneous lupus eryhematosus (SCLE) the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5-30 mJ/cm(2)) equivalent to a moderate to severe sunburn.

Camptothecin induces the transit of FasL trimers to the cell surface in apoptotic HEp-2 cells.

Fas ligand (L) is a membrane protein from the tumor necrosis factor (TNF) family. It induces apoptosis upon contact with its Fas/CD95/APO1 receptor. Trimerization of FasL on the surface of effector cells is essential in the binding of the Fas trimer of the target cells.

Autoantibodies against Cajal bodies in systemic lupus erythematosus.

Background: Cajal bodies (CB) are distinct sub-nuclear domains rich in small nuclear ribonucleoprotein particles (snRNPs); they are involved in pre-mRNA processing. Lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production against different nuclear molecules, including those involved in pre-mRNA processing. The aim of the present investigation is to assess the presence of anti-CB autoantibodies in a cohort of SLE sera.

CENP-B is a conserved gene among vegetal species.

To explore the CENP-B centromere protein in beans, carrots, onions and potatoes, total RNA was isolated and reverse transcribed by PCR, and the cDNA encoding the CENP-B amino terminus domain amplified using CENP-B oligonucleotides. Blots containing PCR products were hybridized with a nick-translated pG/CNPB probe containing a complete human CENP-B gene. In all the plant species, anti-CENP-B antibodies recognized an 80-kDa protein.

Antinuclear antibodies recognize cellular autoantigens driven by apoptosis.

Objective: Present study addresses the issue whether cellular antigens recognised by antinuclear autoantibodies are driven by apoptosis.

Materials And Methods: HEp-2 cells were committed to apoptosis by camptothecin; DNA fragmentation and FasL and Bax expression monitored apoptosis. Autoantigens were probed by indirect immunofluorescence and Western blot with autoantibodies or monoclonals against: DNA, Ro60, La, U1-RNP, CENP-B, DNA Topoisomerase I, Jo-1 and NuMA.

U3 snoRNP associates with fibrillarin a component of the scleroderma clumpy nucleolar domain.

Serum from patients with scleroderma recognizes the clumpy autoantigen. The present studies addressed the issue as to whether the clumpy nucleolar autoantigen recognized by scleroderma serum is fibrillarin-U3 snoRNP. Clones encoding for clumpy autoantigen were immunodetected from a lambdagt11 HeLa cell random-primed library with the serum from a patient with diffuse scleroderma and autoautoantibodies against clumpy autoantigen.