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Objective The aim of the present research was to evaluate the correlation of vertically transmitted IgG antibodies induced by T. cruzi and newborn early outcome assessment, mainly birth weight and gestational age. Methods We performed a cross-sectional study with 183 pregnant women (64 with asymptomatic Chagas disease) and their newborns. Both were subjected to complete clinical examination. Peripheral parasitemia was assessed in mother and neonates by parasite detection through microscopic examination of the buffycoat from mother's peripheral and cord blood. Antibodies induced by T. cruzi, such as anti-FRA, anti-B13, anti-p2[beta] and anti-T. cruzi were assessed by immunoassay. Birth weight, general condition evaluation by APGAR Score and gestational age by Capurro Score, were determined in newborns. Results The rate of stillbirth background and pregnancy-induced hypertension were higher in patients with Chagas disease (p = 0.01 and p = 0.02, respectively). Parasitemia was detectable in 17 mothers and 4 newborns. The newborns of mothers with detectable parasitemia presented decreased gestational age (p = 0.006) and body weight (p = 0.04). Mostly all the mothers with Chagas disease and all their newborns have positive values of antibodies induced by T. cruzi; however, only anti-p2[beta] showed to be related to the presence of complication during pregnancy (OR 2.35, p = 0.036), and to low birth weight (OR 1.55, p = 0.02). Conclusions Low birth weight and decreased postnatal estimation of maturity were related to detectable parasitemia in the mother. Also, vertical transmission of T. cruzi-induced autoantibodies might have clinical implication in newborns given the negative association between anti-p2[beta] values and weight., Author(s): Miguel Hernan Vicco[sup.1] [sup.2] , Luz Rodeles[sup.1] [sup.2] , Gabriela Soledad Capovilla[sup.2] , Melina Perrig[sup.1] , Ana Gabriela Herrera Choque[sup.3] , Ivan Marcipar[sup.1] , Oscar Bottasso[sup.4] , Celeste Rodriguez[sup.3] [...]

In this Review we focus on the initiation of autoantibody production and autoantibody pathogenicity, with a special emphasis on the targeted antigens. Release of intracellular antigens due to excessive cell death or to ineffective clearance of apoptotic debris, modification of self-antigens during inflammatory responses, and molecular mimicry contribute to the initiation of autoantibody production. We hypothesize that those autoreactive B cells that survive and produce pathogenic autoantibodies have specificity for self-antigens that are TLR ligands. Such B cells experience both B cell receptor (BCR) activation and TLR engagement, leading to an escape from tolerance. Moreover, the autoantibodies they produce form immune complexes that can activate myeloid cells and thereby establish the proinflammatory milieu that further negates tolerance mechanisms of both B and T cells., Introduction The first autoantibodies were discovered in the late 1940s, when both antinuclear antibodies (ANAs) and rheumatoid factors (RFs) were described as serum factors that could bind nuclear antigens and [...]

In pemphigus vulgaris, a life-threatening autoimmune skin disease, epidermal blisters are caused by autoantibodies primarily targeting desmosomal cadherins desmoglein 3 (DSG3) and DSG1, leading to loss of keratinocyte cohesion. Due to limited insights into disease pathogenesis, current therapy relies primarily on nonspecific long-term immunosuppression. Both direct inhibition of DSG transinteraction and altered intracellular signaling by p38 MAPK likely contribute to the loss of cell adhesion. Here, we applied a tandem peptide (TP) consisting of 2 connected peptide sequences targeting the DSG adhesive interface that was capable of blocking autoantibody-mediated direct interference of DSG3 transinteraction, as revealed by atomic force microscopy and optical trapping. Importantly, TP abrogated autoantibody-mediated skin blistering in mice and was effective when applied topically. Mechanistically, TP inhibited both autoantibody-induced p38 MAPK activation and its association with DSG3, abrogated p38 MAPK-induced keratin filament retraction, and promoted desmosomal DSG3 oligomerization. These data indicate that p38 MAPK links autoantibody-mediated inhibition of DSG3 binding to skin blistering. By limiting loss of DSG3 transinteraction, p38 MAPK activation, and keratin filament retraction, which are hallmarks of pemphigus pathogenesis, TP may serve as a promising treatment option., Introduction Pemphigus vulgaris (PV) is a life-threatening blistering disease histopathologically characterized by acantholysis, i.e., cleft formation within the epidermis or mucous membranes (1). The disease is caused by autoantibodies predominantly [...]

The aminoacyl-tRNA synthetases are ubiquitously expressed enzymes that catalyze the esterification of amino acids to their cognate tRNAs. Autoantibodies against several aminoacyl-tRNA synthetases are found in autoimmune polymyositis and dermatomyositis patients. Because necrosis is often found in skeletal muscle biopsies of these patients, we hypothesized that cell-death-induced protein modifications may help in breaking immunological tolerance. Since cell death is associated with oxidative stress, the effect of oxidative stress on the main myositis-specific autoantibody target Jo-1 (histidyl-tRNA synthetase; HisRS) was studied in detail. The exposure of Jurkat cells to hydrogen peroxide resulted in the detection of several oxidized methionines and one oxidized tryptophan residue in the HisRS protein, as demonstrated by mass spectrometry. Unexpectedly, the tRNA aminoacylation activity of HisRS appeared to be increased upon oxidative modification. The analysis of myositis patient sera did not lead to the detection of autoantibodies that are specifically reactive with the modified HisRS protein. The results of this study demonstrate that the Jo-1/HisRS autoantigen is modified under oxidative stress conditions. The consequences of these modifications for the function of HisRS and its autoantigenicity are discussed. Key words: Jo-1, histidyl-tRNA synthetase, oxidative stress, posttranslational modification, myositis. Les aminoacyls ARNt synthetases (aaRS) sont des enzymes ubiquistes qui catalysent l'esterification des acides amines a leurs ARNt correspondants. Des autoanticorps diriges contre plusieurs aaRS sont retrouves chez les patients atteints de polymyosite et de dermatomyosite autoimmunes. Parce que de la necrose est souvent trouvee dans les biopsies de muscle squelettique chez ces patients, nous avons emis l'hypothese que des modifications des proteines induites par la mort cellulaire puissent contribuer a briser la tolerance immunitaire. Puisque la mort cellulaire est associee au stress oxydant, l'effet du stress oxydant sur Jo-1 (histidyl-ARNt synthetase; HisRS), la principale cible des autoanticorps specifiques a la myosite, a ete etudie en detail. L' exposition de cellules Jurkat au peroxyde d' hydrogene a resulte en la detection de plusieurs methionines oxydees et d' un residu tryptophane oxyde a l' interieur de la proteine HisRS, comme demontre en spectrometrie de masse. Etonnamment, l'activite d'aminoacylation d'ARNt de HisRS semblait augmentee par l'oxydation. L'analyse des serums de patients atteints de myosite n' a pas permis de detecter des autoanticorps specifiquement reactifs envers la proteine HiRS modifiee. Les resultats de cette etude demontrent que l'autoantigene Jo-1/HisRS est modifie sous des conditions de stress oxydant. Les consequences de ces modifications sur la fonction de HisRS et son autoantigenicite sont discutees. Mots-cles : Jo-1, histidyl-ARNt synthetase, stress oxydant, modification post-traductionnelle, myosite. [Traduit par la Redaction], Introduction Aminoacylation of tRNAs plays a crucial role in the translation of genetic information in polypeptide chains. The generation of aminoacylated-tRNAs depends on the ubiquitously expressed aminoacyl-tRNA synthetases (aaRS), which [...]

1. Introduction In the 19th century, Robert Koch postulated a causal relationship between a pathogenic microbe and a disease [1]. This was later extended to the role of autoantibodies in [...], Molecular mimicry between self and microbial components has been proposed as the pathogenic mechanism of autoimmune diseases, and this hypothesis is proven in Guillain-Barre syndrome. Guillain-Barre syndrome, the most frequent cause of acute neuromuscular paralysis, sometimes occurs after Campylobacter jejuni enteritis. Gangliosides are predominantly cell- surface glycolipids highly expressed in nervous tissue, whilst lipo-oligosaccharides are major components of the Gram-negative bacterium C. jejuni outer membrane. IgG autoantibodies to GM1 ganglioside were found in the sera from patients with Guillain-Barre syndrome. Molecular mimicry was demonstrated between GM1 and lipo-oligosaccharide of C. jejuni isolated from the patients. Disease models by sensitization of rabbits with GM1 and C. jejuni lipo-oligosaccharide were established. Guillain-Barre syndrome provided the first verification that an autoimmune disease is triggered by molecular mimicry. Its disease models are helpful to further understand the molecular pathogenesis as well as to develop new treatments in Guillain-Barre syndrome.

1. Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease that is typified by multiple abnormalities of the immune system, and which results in widespread pathology of multiple organs, including [...], To date, CNS disease and neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. In this review, we focus on a specific mouse model of lupus and the ways in which this model reflects some of the most common manifestations and potential mechanisms of human NP-SLE. The mouse MRL lymphoproliferation strain (a.k.a. MRL/lpr) spontaneously develops the hallmark serological markers and peripheral pathologies typifying lupus in addition to displaying the cognitive and affective dysfunction characteristic of NP-SLE, which may be among the earliest symptoms of lupus. We suggest that although NP-SLE may share common mechanisms with peripheral organ pathology in lupus, especially in the latter stages of the disease, the immunologically privileged nature of the CNS indicates that early manifestations of particularly mood disorders maybe derived from some unique mechanisms. These include altered cytokine profiles that can activate astrocytes, microglia, and alter neuronal function before dysregulation of the blood-brain barrier and development of clinical autoantibody titres.

A new strategy for treating patients who have antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, a severe form of vasculitis, provides the same benefits as the current standard of care used for [...]

Both systemic inflammation and immune dysregulation, including autoantibody production, may occur even in the absence of autoimmune rheumatologic diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Immune dysregulation as [...]