scholarly journals Functional activation of lymphocyte CD44 in peripheral blood is a marker of autoimmune disease activity.

1998 ◽  
Vol 102 (6) ◽  
pp. 1173-1182 ◽  
Author(s):  
P Estess ◽  
H C DeGrendele ◽  
V Pascual ◽  
M H Siegelman
Keyword(s):  
Autoimmune Disease ◽  
Disease Activity ◽  
Peripheral Blood

scholarly journals OP0054 NEW ROLE FOR PROTEINASE 3 IN IL-16 BIOACTIVITY CONTROL IN GRANULOMATOSIS WITH POLYANGIITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 28.1-29
Author(s):  
A. Kerstein-Staehle ◽  
C. Alarcin ◽  
J. Luo ◽  
G. Riemekasten ◽  
P. Lamprecht ◽  
...  
Keyword(s):  
Cell Death ◽  
Western Blot ◽  
Disease Activity ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Granulomatosis With Polyangiitis ◽  
Granulomatous Inflammation ◽  
Proteinase 3 ◽  
Sds Page

Background:The immunomodulatory cytokine IL-16 is increased in several inflammatory and autoimmune diseases1. IL-16 recruits and activates CD4+ immune cells such as T cells, dendritic cells, or monocytes. IL-16 is produced by various immune and non-immune cells, but synthesis and storage of IL-16 is regulated differentially depending on the cell type and stimulation. For its biological activity, IL-16 cleavage by caspase-3 is required1. Necrotizing granulomatous inflammation is a hallmark of granulomatosis with polyangiitis (GPA) with neutrophil dysregulation as a central driver of chronic inflammation and autoimmunity2. Earlier studies showed a correlation between increased serum IL-16 and disease parameters in AAV, including GPA3, but functional evidence for a direct link between IL-16 and neutrophils in granulomatous inflammation is missing so far.Objectives:In this study we aim to identify a functional link between increased IL-16, neutrophils, and the autoantigen proteinase 3 (PR3) with regard to chronic inflammation and autoimmunity in GPA.Methods:IL-16 was measured in sera of GPA patients (n = 40) and healthy controls (HC, n = 50) by ELISA and correlated with clinical features, such as disease activity (BVAS), creatinine, GFR, VDI and PR3-ANCA status. IL-16 protein expression was analyzed in peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) from GPA patients and HC (n = 5, each) by SDS-PAGE and western blot. Binding affinity of recombinant pro-IL-16 to native human PR3 was assessed by microscale thermophoresis. Cleavage of pro-IL-16 by active human PR3 was performed at various time points at 37°C. Cleavage products were analyzed by SDS-PAGE and western blot.Results:Circulating IL-16 was significantly increased in GPA patients compared to HC. Elevated IL-16 positively correlated with BVAS, creatinine, VDI and PR3-ANCA status and negatively correlated with GFR. In PMBC and PMN from GPA and HC we identified different expression patters of precursor and active forms of IL-16. In healthy PBMC we found high amounts of precursor (80kD), pro-IL-16 (55kD) and active IL-16 (17kD). In contrast, PBMC from GPA patients had lower amounts of pro-IL-16 and no active IL-16, indicating activation and secretion of IL-16 due to inflammatory stimulation, as shown earlier5. In GPA PMN we detected no precursor IL-16, but pro-IL-16 and its active form, in contrast to very low amounts of all IL-16 forms in healthy PMN. Processing and release of IL-16 in neutrophils has been linked to apoptosis and secondary necrosis5. By interaction studies we demonstrated direct binding of pro-IL-16 to PR3 with a Kd of 10 nM. In a subsequent cleavage assay we confirmed IL-16 processing by PR3 in a time-dependent manner.Conclusion:Correlation of serum IL-16 with clinical features of GPA suggests that IL-16 is associated with markers of disease activity, tissue damage and autoreactivity. We showed that PBMC and PMN represent a source of IL-16 in GPA. By the identification of PR3 as an additional IL-16-activating enzyme we could demonstrate a potential link between excessive PR3 expression, cell death and IL-16-dependent mechanisms, contributing to chronic granulomatous inflammation and autoimmunity in GPA.References:[1]Glass, W. G. et al. Not-so-sweet sixteen: The role of IL-16 in infectious and immune-mediated inflammatory diseases. J. Interf. Cytokine Res. 26, 511–520 (2006).[2]Millet, A. et al. Proteinase 3 on apoptotic cells disrupts immune silencing in autoimmune vasculitis. J. Clin. Invest. 125, 4107–4121 (2015).[3]Yoon, T. et al. Serum interleukin-16 significantly correlates with the Vasculitis Damage Index in antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Res. Ther. 22, 1–6 (2020).[4]Elssner, A. et al. IL-16 Is Constitutively Present in Peripheral Blood Monocytes and Spontaneously Released During Apoptosis. J. Immunol. 172, 7721–7725 (2004).[5]Roth, S. et al. Secondary necrotic neutrophils release interleukin-16C and macrophage migration inhibitory factor from stores in the cytosol. Cell Death Discov. 1, 15056 (2015).Disclosure of Interests:None declared

scholarly journals AB0037 EXPRESSION OF NEGATIVE CHECKPOINT MOLECULES BTLA AND HVEM IS DYSREGULATED IN AUTOIMMUNE DISEASES

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1321.1-1321
Author(s):  
S. Nagpal ◽  
S. Cole ◽  
A. Floudas ◽  
M. Wechalekar ◽  
Q. Song ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Immune Checkpoint ◽  
Peripheral Blood ◽  
Expression Patterns ◽  
Myeloid Cell ◽  
Dependent Manner ◽  
Research Support

Background:Immune checkpoint blockade with agents targeting CTLA4 and PD-1/PD-L1 alone or in combination has demonstrated exceptional efficacy in multiple cancer types by “unleashing” the cytotoxic action of quiescent, tumor-infiltrating T cells. However, the therapeutic action of these immunotherapies goes hand in hand with the loss of immune tolerance and appearance of immune-related adverse events such as colitis, arthralgia and inflammatory arthritis in responsive patients. Therefore, immune checkpoint molecules have been proposed as targets for the treatment of autoimmune diseases.Objectives:Herein, we interrogate the potential of BTLA/HVEM axis as a target for restoring immune homeostasis in rheumatoid arthritis (RA), Systemic Lupus Erythematosus (SLE) and Sjogren’s Syndrome (SjS) by examining their expression patterns in autoimmune disease tissues.Methods:Message and protein expression of BTLA and HVEM were examined in RA and SLE synovial tissues, SLE cutaneous lesions, SjS salivary glands and peripheral blood samples of autoimmune disease by RNA sequencing and flow cytometry.Results:Tissue dysregulation of the BTLA-HVEM axis was observed: Increased BTLA RNA level in RA synovium, SLE-affected skin, and SjS salivary gland samples, whereas HVEM level was affected only in the RA synovium when compared to unaffected tissues. Detailed immunophenotyping of B, T, and myeloid cell populations in RA, SLE, SjS and healthy control PBMCs revealed differential modulation of the BTLA+ or HVEM+ immune cell subsets in a disease-context dependent manner. SjS patients showed an overall decrease in memory B cells and most of the BTLA+ B cell subsets while a decrease in HVEM+ B cells was observed only in SLE PBMC samples and not RA and SLE samples. Immunophenotyping with a T cell panel exhibited decreased BTLA and HVEM expression on T cell subsets in SjS and SLE but not in RA patients. In addition, protein levels of HVEM were differentially decreased in SLE myeloid cell subsets. Finally, we demonstrate tissue-specific surface expression patterns of BTLA in RA and SLE samples: higher surface BTLA levels on RA and SLE PBMC B cells than matched tissue-derived B cells.Conclusion:Our results demonstrate a dysregulation of the BTLA/HVEM axis in either lesional tissue or peripheral blood in an autoimmune disease context-dependent manner. These results also indicate the potential of targeting BTLA-HVEM axis for the treatment of multiple autoimmune diseases.Disclosure of Interests:Sunil Nagpal Shareholder of: Janssen Pharmaceuticals, Employee of: Janssen Pharmaceuticals, Suzanne Cole Shareholder of: Janssen Research & Development employee, Employee of: Janssen Research & Development employee, Achilleas Floudas: None declared, Mihir Wechalekar Grant/research support from: Grant from Janssen Research & Development, Qingxuan Song Shareholder of: Employee of Janssen Research, Employee of: Employee of Janssen Research, Tom Gordon: None declared, Roberto Caricchio Grant/research support from: Financial grant from Janssen Research & Development, Douglas Veale: None declared, Ursula Fearon: None declared, Navin Rao Shareholder of: Janssen Pharmaceuticals, Employee of: Janssen Pharmaceuticals, Ling-Yang Hao Shareholder of: Employee of Janssen Research, Employee of: Employee of Janssen Research

scholarly journals An Interferon Signature in the Peripheral Blood of Dermatomyositis Patients is Associated with Disease Activity

2007 ◽  
Vol 13 (1-2) ◽  
pp. 59-68 ◽  
Author(s):  
Emily C. Baechler ◽  
Jason W. Bauer ◽  
Catherine A. Slattery ◽  
Ward A. Ortmann ◽  
Karl J. Espe ◽  
...  
Keyword(s):  
Disease Activity ◽  
Peripheral Blood ◽  
Interferon Signature

Simultaneous engagement of FcγIIb and CD22 inhibitory receptors silences targeted B cells and suppresses autoimmune disease activity

2009 ◽  
Vol 47 (1) ◽  
pp. 123-130 ◽  
Author(s):  
Nikolina Mihaylova ◽  
Elisaveta Voynova ◽  
Andrey Tchorbanov ◽  
Pavlina Dolashka-Angelova ◽  
Jagadeesh Bayry ◽  
...  
Keyword(s):  
B Cells ◽  
Autoimmune Disease ◽  
Disease Activity ◽  
Inhibitory Receptors

Abstract P238: Remission/Cure of Autoimmune Diseases by a Lectin Limite Diet Supplemented With Probiotics, Prebiotics, and Polyphenols

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Steven R Gundry
Keyword(s):  
Autoimmune Disease ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Immune Cell ◽  
Molecular Mimicry ◽  
Intestinal Barrier ◽  
Signs And Symptoms ◽  
Omega 3 ◽  
Dietary Lectins ◽  
Limited Diet

All autoimmune diseases are highly associated with increased rates of coronary artery and vascular disease secondary to immune cell attack on epithelial cells. The causes of autoimmune disease (AID) seem to be multifactorial. However, the idea that derangement of the microbiome, breaches of the intestinal barrier (leaky gut) and introduction into the human diet of plant defense molecules such as lectins, which are capable of molecular mimicry, prompted our group to investigate the application of a lectin limited diet, coupled with probiotics and prebiotics (The Pant Paradox Protocol) to impact biomarker proven autoimmune disease activity in humans and their impact on endothelial biomarkers of inflammation. One hundred and two consecutive patients with immunoassay markers of autoimmune disease activity, i.e., RF, anti-CCP, ANA, Histone, etc, and signs and symptoms of RA, Lupus, Sjogrens, Crohns, Colitis, Scleroderma, Mixed Connective Tissue Disease, and biomarkers of endothelial inflammation, were enrolled into a program of elimination of major dietary lectins, consisting of all grains and pseudo grains, beans and legumes, peanuts, cashews, nightshades, squashes, and Casein A1 milk products (The Plant Paradox Program), supplemented with probiotics and prebiotics including resistant starches and polyphenol supplements. All pts initially low Vit D levels and low Omega 3 index and adiponectin levels above 16mg/dl. Biomarkers of inflammation, hs-CRP, TNF-alpha, IL-6, fibrinogen, myeloperoxidase and autoimmune markers were measured every 3 months. 95/102 patients achieved complete resolution of autoimmune markers and inflammatory markers within 9 months. The other 7/102 patients all had reduced markers, but incomplete resolution. 80/102 patients were weaned from all immunosuppressive and/or biologic medications without rebound. We conclude that a lectin limited diet, supplemented with pro and prebiotics, and polyphenols are capable of curing or putting into remission most autoimmune diseases.

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