Antibodies against specific extractable nuclear antigens (ENAs) as diagnostic and prognostic tools and inducers of a profibrotic phenotype in cultured human skin fibroblasts: are they functional?

The importance of systemic sclerosis (SSc) autoantibodies for diagnosis has become recognized by their incorporation into the 2013 ACR/EULAR classification criteria. Clear prognostic and phenotypic association...
Source: Arthritis Research and Therapy - Category: Rheumatology Authors: Tags: Research article Source Type: research

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AbstractObjectiveTo examine changes in the extent of specific patterns of interstitial lung disease (ILD) as they transition from one pattern to another in response to immunosuppressive therapy of Systemic Sclerosis ‐related ILD. (SSc‐ILD)MethodsWe evaluated changes in the quantitative extent of specific lung patterns of ILD using volumetric HRCT scans obtained at baseline and 2 years after therapy in patients treated with either cyclophosphamide (CYC) for 1 year or mycophenolate (MMF) for 2 years in the Scleroderma Lung Study II. ILD patterns included: lung fibrosis (LF), ground glass (GG), honeycombing (HC), and norm...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Full Length Source Type: research
ConclusionOur findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis.
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Original Article Source Type: research
Authors: Petrackova A, Horak P, Radvansky M, Skacelova M, Fillerova R, Kudelka M, Smrzova A, Mrazek F, Kriegova E Abstract Overactivation of the innate immune system together with the impaired downstream pathway of type I interferon-responding genes is a hallmark of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). To date, limited data on the cross-disease innate gene signature exists among those diseases. We compared therefore an innate gene signature of Toll-like receptors (TLRs), seven key members of the interleukin (IL)1/IL1R family, and CXCL8/IL8 in peripheral blood ...
Source: Journal of Immunology Research - Category: Allergy & Immunology Tags: J Immunol Res Source Type: research
ConclusionAnti-DFS70 antibody was more prevalent in the subsets of SARD than BD. This result may be related to the demographic formation of study groups and individual immunological status. More comprehensive studies are needed to investigate the importance of the anti-DFS70 antibody for SARD.Key Points• This study draws attention to the importance of anti-DFS70 antibodies in the diagnostic algorithm in systemic autoimmune rheumatic diseases.• This study emphasizes the further investigation of anti-DFS70 antibodies in undifferentiated connective tissue diseases.• This study emphasizes the need to verify the ...
Source: Clinical Rheumatology - Category: Rheumatology Source Type: research
ConclusionAnti ‐RPA194 antibodies are enriched in anti‐RPC155–positive scleroderma patients without cancer. Since somatic mutations in the gene encodingRPC155 in cancer in scleroderma patients appears to play a role in immune response initiation against RPC155 in those patients, these data raise the possibility that the development of immune responses to both RPC155 and RPA194 may influence clinical cancer emergence. Further study is required to define whether different autoantibody combinations have utility as tools for cancer risk stratification in scleroderma.
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Original Article Source Type: research
AbstractBackgroundDipeptidyl ‐peptidase‐4 (DPP4) identifies a dermal fibroblast lineage involved in scaring during wound healing. The role of DDP4 in tissue fibrosis, however, is unknown. The aim of the present study was to evaluate DPP4 as a potential target for the treatment of fibrosis in systemic sclerosis (SSc).MethodsThe expression of DPP4 was analyzed by real ‐time PCR, immunofluorescence and Western blot. The activity of DPP4 was modulated by overexpression, knockdown and pharmacological inhibition using Sitagliptin and Vildagliptin. The effects of DPP4 inhibition were analyzed in human dermal fibroblasts and...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Full Length Source Type: research
This article aims to discuss the role of RHC in diagnosing pulmonary hypertension, its comparison with other modalities, the procedure, and its role in treatment of connective tissue disorders, especially with a special reference to the Indian context. PMID: 31331141 [PubMed - in process]
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
This study assessed the safety and efficacy of abatacept in patients with diffuse cutaneous systemic sclerosis (dcSSc).MethodsA 12 ‐month, randomized, double‐blind, placebo‐controlled trial with participants randomized in a 1:1 ratio to either abatacept 125 mg subcutaneous or matching placebo, stratified by duration of dcSSc. Escape therapy was allowed at six months for worsening disease. The co‐primary end points were change in modified Rodnan skin score (mRSS) and safety over 12 months. Treatment differences in longitudinal outcomes were assessed using linear mixed models, with outcomes censored after initiation ...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Full Length Source Type: research
AbstractObjectiveThe long interspersed nuclear element 1 (LINE ‐1) encodes two proteins, the RNA‐binding p40 and the endonuclease and reverse transcriptase (ORF2p); both required for LINE‐1 to retrotranspose. In cells expressing LINE‐1, these proteins assemble with the LINE‐1 RNA and additional RNA‐binding proteins, some of which are well‐known au toantigens in patients with systemic lupus erythematosus (SLE). We asked if SLE patients also make autoantibodies against the LINE‐1 p40.MethodsHighly purified p40 protein was used to quantitate IgG autoantibodies in the serum of 172 SLE patients, disease controls...
Source: Arthritis and Rheumatology - Category: Rheumatology Authors: Tags: Full Length Source Type: research
Abstract Methotrexate (MTX) is recognized as the anchor drug in the algorithm treating chronic arthritis (RA, psoriatic arthritis), as well as a steroid sparing agent in other inflammatory conditions (polymyalgia rheumatica, vasculitis, scleroderma). Its main mechanism of action has been related to the increase in extracellular adenosine, which leads to the effects of A2A receptor in M1 macrophages that dampens TNFα and IL12 production and increases IL1Ra and TNFRp75. By acting on A2B receptor on M2 macrophages it enhances IL10 synthesis and inhibits NF-kB signaling. MTX has also been shown to exert JAK inhi...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research
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