scholarly journals Investigation of Newly Diagnosed Drug-Naive Patients with Systemic Autoimmune Diseases Revealed the Cleaved Peptide Tyrosine Tyrosine (PYY 3-36) as a Specific Plasma Biomarker of Rheumatoid Arthritis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Jozsef A. Balog ◽  
Agnes Kemeny ◽  
Laszlo G. Puskas ◽  
Szilard Burcsar ◽  
Attila Balog ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Newly Diagnosed ◽  
Systemic Autoimmune Diseases ◽  
Plasma Cytokines ◽  
Drug Naïve ◽  
Ifn Γ ◽  
Plasma Marker ◽  
Disease Specific

There is a current imperative to reveal more precisely the molecular pathways of early onset of systemic autoimmune diseases (SADs). The investigation of newly diagnosed drug-naive SAD patients might contribute to identify novel disease-specific and prognostic markers. The multiplex analysis of 30 plasma proteins in 60 newly diagnosed drug-naive SADs, such as RA (rheumatoid arthritis, n = 31 ), SLE (systemic lupus erythematosus, n = 19 ), and SSc (systemic scleroderma, n = 10 ) patients, versus healthy controls (HCs, n = 40 ) was addressed. Thirty plasma cytokines were quantified using the Procarta Plex™ panel. The higher expression of IL-12p40, IL-10, IL-13, IFN-γ, M-CSF, IL-4, NTproBNP, IL-17A, BMP-9, PYY (3-36), GITRL, MMP-12, and TNFRSF6 was associated with RA; IL-12p40, M-CSF, IL-4, GITRL, and NTproBNP were higher in SLE; or NTproBNP, PYY (3-36), and MMP-12 were increased in SSc over HCs, respectively. The cleaved peptide tyrosine tyrosine (PYY 3-36) was elevated in RA ( 361.6 ± 47.7  pg/ml) vs. HCs ( 163.96 ± 14.5  pg/ml, mean ± SEM , ∗ ∗ ∗ p = 4 × 10 − 5 ). The CI (95%) was 268.05-455.16 pg/ml for RA vs. 135.55-192.37 pg/ml for HCs. The elevated PYY (3-36) level correlated significantly with the increased IL-4 or GITRL concentration but not with the clinical scores (DAS28, CRP, ESR, RF, aMCV). We are the first to report cleaved PYY (3-36) as a specific plasma marker of therapy-naive RA. Additionally, the multiplex plasma protein analysis supported a disease-specific cytokine pattern in RA, SLE, and SSc, respectively.

scholarly journals Tocilizumab for the Treatment of Rheumatoid Arthritis and Other Systemic Autoimmune Diseases: Current Perspectives and Future Directions

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Atsushi Ogata ◽  
Toshio Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Host Defense ◽  
Lupus Erythematosus ◽  
Therapeutic Strategy ◽  
Case Reports ◽  
Systemic Autoimmune Diseases ◽  
Future Directions ◽  
Pilot Studies ◽  
Beneficial Effects

Interleukin (IL)-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6, when transiently produced, contributes to host defense against acute environmental stress, continuous dysregulated IL-6 production plays a significant pathological role in several systemic autoimmune diseases. In response to the expectation that IL-6 blockade would constitute a novel therapeutic strategy for the treatment of these diseases, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy and the safety of tocilizumab for patients with rheumatoid arthritis, resulting in approval of this innovative biologic for the treatment of rheumatoid arthritis in more than 90 countries worldwide. Pathological analyses of the effect of IL-6 on the development of autoimmune diseases and a considerable number of case reports and pilot studies have also indicated the beneficial effects of this antibody on other systemic autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and large-vessel vasculitis.

scholarly journals Tertiary lymphoid organs in systemic autoimmune diseases:  pathogenic or protective?

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 196 ◽  
Author(s):  
William D. Shipman ◽  
Dragos C. Dasoveanu ◽  
Theresa T. Lu
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Lymphoid Organs ◽  
T And B Cells ◽  
Systemic Lupus ◽  
Disease Pathogenesis ◽  
Systemic Autoimmune Diseases ◽  
Effector Cells ◽  
Secondary Lymphoid Organs

Tertiary lymphoid organs are found at sites of chronic inflammation in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. These organized accumulations of T and B cells resemble secondary lymphoid organs and generate autoreactive effector cells. However, whether they contribute to disease pathogenesis or have protective functions is unclear. Here, we discuss how tertiary lymphoid organs can generate potentially pathogenic cells but may also limit the extent of the response and damage in autoimmune disease.

Biological therapy of arthritis and systemic autoimmune diseases

2007 ◽  
Vol 148 (Supplement-1) ◽  
pp. 63-70 ◽  
Author(s):  
László Tamási ◽  
Zoltán Szekanecz
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Biological Therapy ◽  
Systemic Autoimmune Diseases ◽  
Tnf Α ◽  
Spondylitis Ankylopoetica

A biológiai terápia lényege, hogy a gyulladás egyetlen, jól meghatározott pontján (pl. egy adott citokin szintjén) hat. Ezáltal a sokszor igen bonyolult mechanizmusokból álló patogenetikai hálózatot egy adott ponton szakítja meg. Ma a rheumatoid arthritis a biológiai terápia szempontjából modellbetegség, mivel a legtöbb szerrel ebben a kórképben próbálkoztak. Ezt követően egyéb arthritisekben (pl. spondylitis ankylopoetica, psoriasisos arthropathia), majd egyes szisztémás autoimmun kórképekben (pl. szisztémás lupus erythematosus, scleroderma, myositisek, vasculitisek, Sjögren-szindróma stb.) kezdték el alkalmazni. A legtöbb kórkép esetében egy központi szereppel bíró citokin, a tumornekrózis faktor-α (TNF-α) gátlószerei állnak a terápia középpontjában. Azonban a biológiai terápia megtervezésekor az adott kórkép patogenezisét (pl. döntően Th1 vagy Th2 jellegét) figyelembe kell venni. Nem véletlen, hogy amíg egyes kórképekben (pl. rheumatoid arthritis, spondylitis ankylopoetica, psoriasis, polymyositis, polyarticularis juvenilis arthritis) döntően a TNF-blokkolók és a T-sejtek elleni gátlás vált be, addig másoknál (pl. lupus, Sjögren-szindróma, dermatomyositis) a B-sejt elleni terápia kecsegtet sikerrel. Ezen összefoglalóban a szerzők áttekintik az arthritisek és szisztémás autoimmun kórképek biológiai terápiájára vonatkozó legfontosabb adatokat. Kitérnek az alkalmazott szerek tulajdonságaira, a hatékonyság és biztonságosság kérdéseire egyaránt.

scholarly journals Serum biomarker profile orchestrating the seroconversion status of patients with autoimmune diseases upon planned primary 17DD Yellow fever vaccination

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ismael Artur da Costa-Rocha ◽  
Ketty Lysie Libardi Lira Machado ◽  
Ana Carolina Campi-Azevedo ◽  
Andréa Teixeira-Carvalho ◽  
Vanessa Peruhype-Magalhães ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Neutralizing Antibody ◽  
Serum Biomarkers ◽  
Serum Biomarker ◽  
Time Points ◽  
Inflammatory Status ◽  
Biomarker Response ◽  
Ifn Γ ◽  
A Prospective Study

AbstractThe present study aimed to investigate whether the serum biomarkers of immune response orchestrate the seroconversion status in patients with autoimmune diseases (AID) upon planned primary 17DD-YF vaccination. For this purpose a total of 161 individuals were enrolled in a prospective study, including patients with Rheumatoid Arthritis (RA = 38), Spondyloarthritis (SpA = 51), Systemic Lupus Erythematosus (SLE = 21) and Sjögren’s Syndrome (SS = 30) along with a group of healthy controls (HC = 21). Analysis of plaque reduction neutralization test (PRNT) titers and seropositivity rates along with the 17DD-YF viremia and serum biomarkers were carried out at distinct time points (D0/D3–4/D5–6/D7/D14–28). The results demonstrated an overall lower PRNT titer and seropositivity rate (170 vs. 448; 77 vs. 95%) in AID as compared to HC, especially in SpA and SLE subgroups. No significant differences were observed in the viremia levels amongst groups. In general, a more prominent serum biomarker response was observed in AID as compared to HC, throughout the timeline kinetics. Remarkably, AID/PRNT(−) exhibited higher levels of several biomarkers at baseline as compared to AID/PRNT+. Moreover, while AID/PRNT(+) exhibited earlier increase in serum biomarkers at D3–4/D5–6, the AID/PRNT(−) displayed higher response at later time points (D7/D14–D28). Of note, a synchronic increase of IFN-γ at the peak of viremia (D5–6) was observed in HC and AID/PRNT(+) groups, whereas a later asynchronous IFN-γ response was reported for AID/PRNT(−) at D7. The biomarker profile tends to deflate at post-vaccination timeline, highlighting a putative immunomodulatory effect of live attenuated 17DD-YF vaccine in AID/PRNT(+), but not in AID/PRNT(−). Altogether these data suggested that inflammatory status prior vaccination, low IFN-γ at viremia peak and the occurrence of asynchronous biomarker storm after 17DD-YF vaccination may orchestrate the lack of neutralizing antibody response γ.

scholarly journals DNA Damage Response and Oxidative Stress in Systemic Autoimmunity

2019 ◽  
Vol 21 (1) ◽  
pp. 55 ◽  
Author(s):  
Vassilis L. Souliotis ◽  
Nikolaos I. Vlachogiannis ◽  
Maria Pappa ◽  
Alexandra Argyriou ◽  
Panagiotis A. Ntouros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Dna Damage ◽  
Autoimmune Diseases ◽  
Dna Damage Response ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Systemic Autoimmune Diseases ◽  
Damage Response

The DNA damage response and repair (DDR/R) network, a sum of hierarchically structured signaling pathways that recognize and repair DNA damage, and the immune response to endogenous and/or exogenous threats, act synergistically to enhance cellular defense. On the other hand, a deregulated interplay between these systems underlines inflammatory diseases including malignancies and chronic systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Patients with these diseases are characterized by aberrant immune response to self-antigens with widespread production of autoantibodies and multiple-tissue injury, as well as by the presence of increased oxidative stress. Recent data demonstrate accumulation of endogenous DNA damage in peripheral blood mononuclear cells from these patients, which is related to (a) augmented DNA damage formation, at least partly due to the induction of oxidative stress, and (b) epigenetically regulated functional abnormalities of fundamental DNA repair mechanisms. Because endogenous DNA damage accumulation has serious consequences for cellular health, including genomic instability and enhancement of an aberrant immune response, these results can be exploited for understanding pathogenesis and progression of systemic autoimmune diseases, as well as for the development of new treatments.

scholarly journals Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Qingjun Pan ◽  
Linjie Guo ◽  
Jing Wu ◽  
Jun Cai ◽  
Huanjin Liao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Lupus Nephritis ◽  
Inflammatory Response ◽  
Lupus Erythematosus ◽  
Serum Levels ◽  
Clinical Parameters ◽  
Newly Diagnosed ◽  
Systemic Lupus ◽  
Novel Therapeutic

In order to investigate the association between IgG4 autoantibody and complement abnormalities in systemic lupus erythematosus (SLE), 72 newly diagnosed SLE patients, 67 rheumatoid arthritis (RA) patients, and 41 healthy normals were employed. Serum levels of antinuclear IgG4 and IgG4-specific IgM-rheumatoid factor (RF) were measured, and the correlations between serum levels of antinuclear IgG4 and several clinical parameters were analyzed. Also, the levels of IgG subclasses, C1q, and C3 deposition in lupus nephritis (LN) were detected. The results showed that serum levels of antinuclear IgG4 were higher in SLE patients relative to healthy normals (P<0.01). Serum levels of antinuclear IgG4 in SLE patients were positively correlated with serum levels of total IgG4, albumin, and C3 (r=0.61,P<0.05;r=0.40,P<0.05; andr=0.54,P<0.05, resp.) and negatively correlated with 24-hour urinary protein (r=0.49,P<0.05). Serum levels of IgG4-specific IgM-RF were higher in RA patients than in SLE patients (P<0.001). Also, the ratio of the deposition score for IgG4/(IgG1 + IgG2 + IgG3 + IgG4) was negatively correlated with the score for C1q and C3 deposition in LN (r=0.34,P<0.05;r=0.51,P<0.01, resp.). In summary, the IgG4 autoantibody may dampen the inflammatory response in SLE, thus maybe providing a novel therapeutic target for SLE.

scholarly journals Identification of a Shared Microbiomic and Metabolomic Profile in Systemic Autoimmune Diseases

2019 ◽  
Vol 8 (9) ◽  
pp. 1291 ◽  
Author(s):  
Bellocchi ◽  
Fernández-Ochoa ◽  
Montanelli ◽  
Vigone ◽  
Santaniello ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
High Performance ◽  
16S Rrna Gene Sequencing ◽  
Study Groups ◽  
Mass Spectrometry Analysis ◽  
Rrna Gene ◽  
Operating Characteristics ◽  
Systemic Autoimmune Diseases ◽  
Spectrometry Analysis

Dysbiosis has been described in systemic autoimmune diseases (SADs), including systemic lupus erythematosus (SLE), Sjögren’s syndrome (SjS), and primary anti-phosholipid syndrome (PAPS), however the biological implications of these associations are often elusive. Stool and plasma samples from 114 subjects, including in SLE (n = 27), SjS (n = 23), PAPs (n = 11) and undifferentiated connective tissue (UCTD, n = 26) patients, and geographically-matched healthy controls (HCs, n = 27), were collected for microbiome (16s rRNA gene sequencing) and metabolome (high-performance liquid chromatography coupled to mass spectrometry) analysis to identify shared characteristics across diseases. Out of 130 identified microbial genera, a subset of 29 bacteria was able to differentiate study groups (area under receiver operating characteristics (AUROC) = 0.730 ± 0.025). A fair classification was obtained with a subset of 41 metabolic peaks out of 254 (AUROC = 0.748 ± 0.021). In both models, HCs were well separated from SADs, while UCTD largely overlapped with the other diseases. In all of the SADs pro-tolerogenic bacteria were reduced, while pathobiont genera were increased. Metabolic alterations included two clusters comprised of: (a) members of the acylcarnitine family, positively correlating with a Prevotella-enriched cluster and negatively correlating with a butyrate-producing bacteria-enriched cluster; and (b) phospholipids, negatively correlating with butyrate-producing bacteria. These findings demonstrate a strong interaction between intestinal microbiota and metabolic function in patients with SADs.

A comparative study on clinical and serological characteristics between patients with rhupus and those with systemic lupus erythematosus and rheumatoid arthritis

Lupus ◽  
2020 ◽  
Vol 29 (10) ◽  
pp. 1216-1226
Author(s):  
Beatriz Frade-Sosa ◽  
Javier Narváez ◽  
Tarek Carlos Salman-Monte ◽  
Raul Castellanos-Moreira ◽  
Vera Ortiz-Santamaria ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Disease Duration ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Classification Criteria ◽  
Systemic Lupus ◽  
Cross Sectional

Background The concomitant presence of two autoimmune diseases – systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) – in the same patient is known as rhupus. We evaluated a group of patients with rhupus to clarify further their clinical, serological and immunogenic features in a multi-centre cohort. In addition, the study aimed to explore the utility of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in our group of patients with rhupus. Methods This was a cross-sectional study. We included rhupus patients from 11 different rheumatology departments, and compared them to SLE and RA patients at a ratio of 2:1. All information was recorded following a pre-established protocol. Results A total of 200 patients were included: 40 rhupus patients and 80 each of SLE and RA patients as controls. Disease duration was similar among SLE and rhupus groups (around 13 years), but the RA group had a significantly lower disease duration. Main clinical manifestations were articular (94.2%), cutaneous (77.5%) and haematological (72.5%). Rhupus patients had articular manifestations similar to those expected in RA. Only 10% of rhupus patients had renal involvement compared with 25% of those with SLE ( p < 0.05), while interstitial lung disease was more common in patients affected by RA. The 2019 EULAR/ACR SLE criteria were met in 92.5% of the rhupus patients and in 96.3% of the SLE cohort ( p > 0.05). Excluding the joint domain, there were no differences between the numbers of patients who met the classification criteria. Conclusion Rhupus patients follow a particular clinical course, with full expression of both SLE and RA in terms of organ involvement, except for a lower prevalence of kidney affection. The new 2019 EULAR/ACR SLE criteria are not useful for differentiating SLE and rhupus patients. A new way of classifying autoimmune diseases is needed to identify overlapping clusters.

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