Welcome to the Autoimmunity 2021 Congress Calendar

Background and Aims

To critically review the contemporary and earlier literature descring the so-called Sick Building Syndrome and to underpin some controversaries with regard to this dubious terminology

Methods

Medline and PubMed search

Results

Contemporary literature suggests that indoor air infestation with dampness microbiota is a real health hazard that starts with the so-called SBS, but when the exposure continues, it may cause an irreversible Dampness and Mold Hypersensitivity Syndrome with a great variety of clinical presentations and involving practically all organs. The underlying pathophysiology is chronic inflammation and dysregalation of immune, endocrine and metabolic functions.

Conclusions

SBS/DMHS are not primarily psychological disturbances. Neither these conditions are the so-called functional disorders.

New imaging techniques, clinical toxicology and chip-based detection of autoantibodies should be further developed to help clinical diagnosis of SBS/DMHS

Background and Aims

Genetic polymorphism and methylation-dependent overexpression of Rab4A influences mechanistic target of rapamycin (mTOR) activation that in turn controls immune cell lineage specification and constitutes an effective treatment target for autoimmunity in systemic lupus erythematosus (SLE).

Methods

To determine the impact of Rab4A during lupus pathogenesis, we generated mice with constitutively active Rab4A^Q72Lalleles or lacking expression of Rab4A in T cells (Rab4A-KO^CD4Cre) on the C57Bl/6 background and further backcrossed them onto the lupus-prone SLE1.2.3 triple-congenic (B6.TC) line.

Results

Activation of Rab4A accelerated the production of antinuclear antibodies (ANA) and antiphospholipid antibodies (aPL), anti-cardiolipin (ACLA) and anti-β₂ glycoprotein I autoantibodies (anti-β₂GPI), proteinuria, glomerulonephritis, and neurobehavioral dysfunction, while deletion of Rab4A in T cells abrogated pathogenesis. Dual mTORC1/mTORC2 activation was restrained in CD4 T cells, while mTORC2 was selectively blocked in CD8 T cells of B6.TC/Rab4A-KO^CD4Cre mice. By contrast, pristane-inducible ANA, ACLA and anti-β₂GPI production and pulmonary vasculitis (PV) were increased in Rab4A-KO^CD4Cre mice but blocked in Rab4A^Q72L mice relative to age-matched wildtype (WT) controls. However, intrahepatic lymphocytic infiltration and vasculitis were enhanced in Rab4A^Q72L but diminished in Rab4A-KO^CD4Cre mice. Thymus-derived FoxP3⁺Helios⁺ Tregs and mTORC1⁺/mTORC2⁺ CD4⁺CD25⁺ Tregs were expanded in Rab4A^Q72L mice but depleted in Rab4A-KO^CD4Cre mice. IL-17-producing CD11b⁺ pro-inflammatory macrophages were accumulated in the spleen and Gr1⁺ neutrophils were expanded in the lung of Rab4A-KO^CD4Cre mice. Rapamycin completely abrogated nephritis and improved neurobehavioral dysfunction in B6.TC/Rab4A^Q72L mice but failed to block PV in WT or Rab4A-KO^CD4Cre mice.

Conclusions

The findings suggest that Rab4A impacts organ-specific lupus pathogenesis through modulating mTOR-dependent pro-inflammatory T-cell development and trafficking.

Background and Aims

Biopolymers are non-biocompatible allogeneic materials that have signs and symptoms locally and systemically. Those materials produce systemic inflammatory autoimmune syndrome induced by adjuvants

Methods

A study of patients between year 2017 and 2019 is carried out in patients with biopolymer administration; open technique was performed by the author at Nueva Clinica los Cedros in Bogotá Colombia. 120 patients were evaluated in a period between 2017 and 2019, ages between 24 and 74 years. Clinical evaluation with major and minor criteria for Asia syndrome described by Schoenfeld and Agmon Levin and quantitative rheumatological tests were performed: antinuclear antibodies, lupic anticoagulant, rheumatoid factor, lactate dehydrogenase, serum complement c3 – c4, anti SLC – 70 antibodies and HLA-B27; post-surgical evaluation of symptoms and rheumatic control studies were evaluated 3 to 6 months after open surgical biopolymer extraction.

Results

Pre-surgical evaluation of symptoms manifested by patients during anamnesis and positive rheumatologic findings were documented, analysis showed most commonly expressed symptoms: Myalgia, arthralgia, asthenia, Adinamia, hair loss, fever or pyrexia, preoperative rheumatologic altered exams are: antinuclear antibodies (60.8%). Lupus anticoagulant (40.8%) lactic dehydrogenase (31.6%) serum complement C3 and C4 (13.3%), rheumatoid factor (9.1%), HLA-B27 (4.1%) and anti SLC 70 antibodies (4.1%). Objective results show symptom improvement and quantitative rheumatologic changes after resection of non-biocompatible allogeneic material.

Conclusions

qualitative analysis of clinical and quantitative results of pre and post-surgical rheumatologic studies of patients with biopolymers allow to conclude that open buttock technique has clinical benefits in terms of improvement and palliation of symptoms and inmunologic response

Background and Aims

The referral of patients with positive anti-nuclear antibody (ANA) tests to tertiary care specialists has been criticized as an inappropriate use of medical resources thereby increasing the need to explore efficient testing methods. Here we assess the utility of a novel particle based multi-analyte technology (PMAT) in comparison to a chemiluminescent immunoassay (CIA) for the detection of anti-DFS70 antibodies.

Methods

Over a duration of three years, 15,357 patients were referred through a central triage (CT) system for review by tertiary care specialists. 643/15,357 (4.1%) were positive for HEp-2-ANA. 220/643 (34.2%) cases were tested using PMAT (centromere B, dsDNA, Jo-1, ribosomal-P, RNP, Ro60, Ro52, Scl-70, Sm, SSB, and DFS70) and CIA (QUANTA Flash, Inova Diagnostics, San Diego, CA) for anti-DFS70 antibodies.

Results

Out of the 220 ANA positive individuals, 52 (23.6%), 16 (7.3%) and 152 (69.1%) cases were defined as ANA-associated rheumatic disease (AARD), unresolved, or non-AARD cases, respectively. Out of 220 ANA positive cases, 48 (21.8%) and 42 (19.1%) were anti-DFS70 positive on PMAT and CIA, respectively [total percent agreement 95.5% [95%CI: 91.8-97.5]; kappa of 0.86 [95% CI 95% CI 77.8-94.3] and spearman’s rho 0.642). All 21 (9.5%) monospecific DFS70 positive were positive on CIA and a majority (20/21) of the cases were non-AARD, OR 6.9 [95% CI 1.1-41.3].

Conclusions

This is the first study to use PMAT to evaluate the serological and clinical features of patients referred through a CT system because of a positive ANA where PMAT and established CIA systems showed a high level of agreement for anti-DFS70 positivity.

Background and Aims

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potent immunoregulatory enzyme that catalyses the degradation of the essential amino acid tryptophan (Trp) along the kynurenines pathway. Significant changes in systemic Trp catabolism have been reported in many diseases, including cancer and autoimmunity. In female nonobese (NOD) mice, a model for human type 1 diabetes (T1D), IDO1 expression and hence immune tolerance to pancreatic b-cell autoantigens are defective in conventional dendritic cells stimulated with IFN-γ, the main IDO1 inducer. Analogously to the impairment of IDO1 function observed in NOD mice, the existence of the IDO1 defect in human peripheral blood mononuclear cells (PBMCs) of T1D patients has been proven.

Methods

We monitored the IDO1 expression and activity in PBMCs of children with T1D as compare to age-matched control subject, in response to IFN-γ.

Results

Results from the analysis of IDO1 activity demonstrated that the majority of patients with T1D is characterized by defective Trp catabolism. Moreover, this defect is mainly imputable to a SOCS3-mediated, dysregulated IL-6 signaling that would favor IDO1 proteasomal degradation in inflammatory environments. We thus measured IDO1 expression and activity in PBMCs co-incubated with IFN-γ and Tocilizumab (TCZ), a licensed IL-6 receptor blocker.

Conclusions

Results showed that TCZ is able to restore normal levels of IDO1 catalytic activity in response to IFN-γ in approximately 30% of the examined T1D population. Besides further confirming the heterogeneity of the disease, our data indicate the existence of a subset of individuals with T1D who may gain clinical benefit in restoring immunoregulatory mechanisms by treatment with tocilizumab.

Background and Aims

In the central nervous system (CNS) complement has functions that go beyond the immune surveillance. It's involved in the control of the synaptic plasticity, dictating neurogenesis and synaptic modelling, but the molecular mechanisms, particularly those occurring presynaptically, are so far poorly investigated. Owing to shed light on these aspects, we investigated i) whether complement can affect the release of neurotransmitters from presynaptic nerve endings (synaptosomes) and ii) if antigen-antibody complexes at the outer side of synaptosomal plasmamembranes can trigger additional complement-induced responses.

Methods

Mouse synaptosomes were exposed to complement in superfusion and the release of glutamate, GABA, noradrenaline and acetylcholine quantified. When indicated, synaptosomes were preincubated with antibodies recognizing the outer sequence of NMDA and AMPA receptors subunits.

Results

Complement released glutamate in a dilution-dependent, carrier-mediated manner from mouse cortical, hippocampal, cerebellar and spinal cord synaptosomes. Complement releasing activity was restricted to glutamatergic terminals since the release of GABA, noradrenaline and acetylcholine was not affected. The incubation of synaptosomes with antibodies recognizing the outer sequence of the GluA2 and GluA3 AMPA receptor proteins significantly increased the complement-evoked release efficiency in a C1q-dependent fashion, while exposure to anti-GluN1 and anti-GluN2B NMDA receptor proteins antibodies reduced it. The last effect is linked to an antibody-induced internalization of NMDA receptors, unveiling a NMDA-mediated component of the complement releasing activity.

Conclusions

Our observations improve the knowledge of the complement-mediated control of glutamatergic transmission at chemical synapsis and of the molecular events underlying the cross-talk linking the immune system and the CNS.