Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?

Didier, Kévin; Bolko, L.; Giusti, Delphine; Toquet, S.; Robbins, A.; Antonicelli, Frank; Servettaz, Amélie

doi:10.3389/fimmu.2018.00541

Cited by 144 publications

(127 citation statements)

References 239 publications

(321 reference statements)

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“…witnessing the disease rather than causing it, analogous to some AuAbs associated with connective tissue diseases (reviewed in Ref. 54), or exhibit an additive/synergistic action within a putative constellation of pathogenic PV AuAbs required to overcome the natural resistance of keratinocytes to dysadhesion.…”

Section: Autoimmunity Of Non-desmoglein Pemphigusmentioning

confidence: 99%

Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody–negative pemphigus vulgaris

Chernyavsky¹,

Amber

Agnoletti³

et al. 2019

Journal of Biological Chemistry

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Edited by Peter Cresswell Pemphigus vulgaris (PV) is a potentially lethal mucocutaneous blistering disease characterized by IgG autoantibodies (AuAbs) binding to epidermal keratinocytes and inducing this devastating disease. Here, we observed that non-desmoglein (Dsg) AuAbs in the sera of patients with Dsg1/3 AuAb-negative acute PV are pathogenic, because IgGs from these individuals induced skin blistering in neonatal mice caused by suprabasal acantholysis. Serum levels of AuAbs to desmocollin 3 (Dsc3), M3 muscarinic acetylcholine receptor (M3AR), and secretory pathway Ca 2؉/ Mn 2؉ -ATPase isoform 1 (SPCA1) correlated with the disease stage of PV. Moreover, AuAb absorption on recombinant Dsc3, M3AR, or SPCA1 both prevented skin blistering in the passive transfer of AuAbs model of PV in BALB/c mice and significantly decreased the extent of acantholysis in a neonatal mouse skin explant model. Although acantholytic activities of each of these immunoaffinity-purified AuAbs could not induce a PV-like phenotype, their mixture produced a synergistic effect manifested by a positive Nikolskiy sign in the skin of neonatal mice. The downstream signaling of all pathogenic non-Dsg AuAbs involved p38 mitogen-activated protein kinase (MAPK)-mediated phosphorylation and elevation of cytochrome c release and caspase 9 activity. Anti-Dsc3 and anti-SPCA1 AuAbs also activated SRC proto-oncogene, nonreceptor tyrosine kinase (SRC). Of note, although a constellation of non-Dsg AuAbs apparently disrupted epidermal integrity, elimination of a single pathogenic AuAb could prevent keratinocyte detachment and blistering. Therefore, anti-Dsg1/3 AuAb-free PV can be a model for elucidating the roles of non-Dsg antigenspecific AuAbs in the physiological regulation of keratinocyte cell-cell adhesion and blister development.

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Section: Autoimmunity Of Non-desmoglein Pemphigusmentioning

confidence: 99%

Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody–negative pemphigus vulgaris

Chernyavsky¹,

Amber

Agnoletti³

et al. 2019

Journal of Biological Chemistry

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“…RF and ACPA are the main serological markers for RA, which have been included in the classification criteria. Since RF can also be found in other connective tissue diseases and some chronic infectious diseases, it is not a specific diagnostic marker for RA.…”

Section: Biomarkers Of Early Ramentioning

confidence: 99%

The challenges of early diagnosis and therapeutic prediction in rheumatoid arthritis

Zhao

2018

Int J of Rheum Dis

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“…ACTDs are often associated with difficulties in diagnosis. Circulating antibodies in the blood often help in the patient classification and are included in the criteria for the classification of these diseases [1]. The most common ACTD is rheumatoid arthritis (affecting 1/100 people), whereas one of the least frequent is MCTD.…”

Section: Introductionmentioning

confidence: 99%

The Serum Cell-Free microRNA Expression Profile in MCTD, SLE, SSc, and RA Patients

Stypińska

Wajda

Walczuk

et al. 2020

JCM

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Mixed connective tissue disease (MCTD) is a rare disorder characterized by symptoms that overlap two or more Autoimmune Connective Tissue Diseases (ACTDs). The aim of this study was to determine whether miRNAs participating in the TLRs signaling pathway could serve as biomarkers differentiating MCTD or other ACTD entities from a healthy control group and between groups of patients. Although the selected miRNA expression level was not significantly different between MCTD and control, we observed that miR-126 distinguishes MCTD patients from all other ACTD groups. The expression level of miRNAs was significantly higher in the serum of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients compared to controls. The miR-145 and -181a levels distinguished RA from other ACDT patients. miR-155 was specific for SLE patients. MiR-132, miR-143, and miR-29a distinguished RA and SLE patients from the systemic sclerosis (SSc) group. Additionally, some clinical parameters were significantly related to the miRNA expression profile in the SLE group. SLE and RA are characterized by a specific serum expression profile of the microRNAs associated with the Toll-like receptors (TLRs) signaling pathway. The analysis showed that their level distinguishes these groups from the control and from other ACTD patients. The present study did not reveal a good biomarker for MCTD patients.

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Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?

Cited by 144 publications

References 239 publications

Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody–negative pemphigus vulgaris

Synergy among non-desmoglein antibodies contributes to the immunopathology of desmoglein antibody–negative pemphigus vulgaris

The challenges of early diagnosis and therapeutic prediction in rheumatoid arthritis

The Serum Cell-Free microRNA Expression Profile in MCTD, SLE, SSc, and RA Patients

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