scholarly journals VEGF and IL-6 correlation in POEMS: a potential upcoming marker of active disease and early autologous BMT response.

2022 ◽  
Vol 14 (1) ◽  
pp. e2022007
Author(s):  
Luca Laurenti ◽  
Idanna Innocenti ◽  
Giulia Benintende ◽  
Annamaria Tomasso ◽  
Francesco Autore ◽  
...  

Introduction: VEGF function may be responsible for most POEMS manifestations, and it is considered a reliable marker of disease. COVID-19 era arose increasing interest for other inflammatory cytokines, with particular focus on Interleukin-6; VEGF production is stimulated by IL-6 and IL1β, whose concentrations appear to be elevated in clonal plasma cells. Objectives: This study aims to simultaneously evaluate VEGF and IL-6 values in patients (pts) with POEMS at different stages of the disease to find a correlation between them. Methods: We performed a monocentric study, measuring serum levels of VEGF and IL-6 in 8 POEMS pts at different time points of the disease. Results: We observed elevated serum levels of both VEGF and IL-6 in three pts before transplant, while the day after the infusion of autologous stem cells, we observed a steep decrease of both serum markers. Among the four-pts tested only after transplant, two presented with a consensual level of VEGF and IL-6, while the others did not correlate. One patient observed at POEMS diagnosis, during active disease, presented with strikingly high levels of both serum markers. Conclusions: So far, to the best of our knowledge, IL-6 could be considered as a marker of active disease and reliable up to the very first months after BMT, after which its accuracy appears to be lost due to unknown factors, still to be investigated.

2018 ◽  
Vol 34 (12) ◽  
pp. 891-897 ◽  
Author(s):  
Doha M Beltagy ◽  
Kadry M Sadek ◽  
Amal S Hafez

β-glucuronidase (BG) activity is a promising biomarker for diagnosis and prognosis after exposure to organophosphorous (OP) pesticides. The aim of this study was to evaluate the changes in serum BG activity in patients with acute OP poisoning and to determine whether these changes correlate with the severity of poisoning. Thirty patients with anticholinesterase pesticide poisoning were included, besides 10 healthy volunteers as a control group. Serum activities of butyrylcholinesterase (BuChE) and BG were measured for each subject on admission, then after 12 and 24 h. Serum levels of BuChE and BG in poisoned patients were significantly different from the control subjects; these differences persisted in repeated measurements. Moreover, the serum levels showed significant differences within each group of the three time points. A significant negative correlation was found between the serum activities of BuChE and BG in all groups at the three time points. In conclusion, serum BG activity seems a reliable marker for OP poisoning even when measured at 24 h after poisoning.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Kazuichi Okazaki ◽  
Hisanori Umehara

Recent studies suggest simultaneous or metachronous lesions in multiorgans characterized by elevated serum levels of IgG4 and abundant infiltration of IgG4-positive plasma cells with various degrees of fibrosis. Two Japanese research committees for IgG4-RD, one from fibrosclerosis (Okazaki team) and the other from lymph proliferation (Umehara team) supported by the “Research Program for Intractable Disease” of the Ministry of Health, Labor, and Welfare of Japan, have agreed with the unified nomenclature as “IgG4-RD” and proposed the comprehensive diagnostic criteria (CDC) for IgG4-RD. Validation of the CDC demonstrated satisfactory sensitivity for the practical use of general physicians and nonspecialists but low sensitivity in the organs to be difficult in taking biopsy specimens such as type1 autoimmune pancreatitis (IgG4-related AIP), compared with IgG4-related sialadenitis/dacryoadenitis (Mikulicz's disease) and IgG4-related kidney disease. Although the diagnostic criteria covering all IgG4-RD are hard to be established, combination with the CDC and organ-specific diagnostic criteria should improve sensitivity.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yasuharu Sato ◽  
Tadashi Yoshino

Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135?mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+plasma cells (IgG4+/IgG+plasma cell ratio >40%). However, patients with hyper-interleukin (IL-) 6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1359.1-1360
Author(s):  
M. Sagiv ◽  
G. Slobodin ◽  
T. Khatib ◽  
I. Rosner ◽  
M. Rozenbaum ◽  
...  

Background:Elevated serum levels of interleukin (IL)-22 were reported in patients with ankylosing spondylitis (AS).[1]IL-22 was also reported to drive the osteogenic differentiation of mesenchymal stem cells.[2]Objectives:To confirm the fact that serum levels of IL-22 are elevated in AS patients and to examine the relationship between concentrations of IL-22 and degree of radiographic progression in AS patients.Methods:Seventeen male patients with established AS of more than 4 years duration signed the informed consent and donated 10 ml of peripheral blood. Demographic data was collected from patient’s charts. Disease activity indices were calculated for all patients and radiographic disease progression was calculated as mSASS. A control group included 6 healthy persons and 4 patients with advanced diffuse idiopathic skeletal hyperostosis (DISH). Serum levels of IL-22 were tested using enzyme-linked immunosorbent assay. Intergroup differences were examined using the Mann-Whitney test, while correlations were calculated using Pearson correlation coefficient.Results:Serum IL-22 levels were remarkably elevated in patients with AS, comparing to healthy individuals and patients with DISH (p=0.005). However, increased concentrations of IL-22 did not correlate with the degree of radiographic progression or AS disease activity indices, nor with disease duration or patient’s age. Presence of diarrhea, psoriasis, uveitis, or elevated levels of C-reactive protein did not influence the levels of IL-22 as well. More AS patients with elevated serum IL-22 were smokers (p=0.05).Fig. 1.Serum levels of interleukin 22 (pg/ml)Conclusion:The serum levels of IL-22 are elevated in patients with AS. It seems that smoking can be related to the elevated levels of serum IL-22 in AS. The significance of this data is unclear and further research is needed.References:[1]Zhang L, Li Y gang, Li Y hua, Qi L, Liu X guang, Yuan C zhong, et al. Increased frequencies of th22 cells as well as th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS One. 2012;7(4).[2]El-Zayadi AA, Jones E, Churchman S, Baboolal T, Cuthbert R, El-Jawhari J, et al. Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies. Rheumatology. 2016 Dec 10;56.Disclosure of Interests:None declared


Lupus ◽  
2016 ◽  
Vol 26 (2) ◽  
pp. 139-149 ◽  
Author(s):  
H Tydén ◽  
C Lood ◽  
B Gullstrand ◽  
A Jönsen ◽  
F Ivars ◽  
...  

Objectives Systemic lupus erythematosus (SLE) is associated with elevated levels of S100A8/A9, pro-inflammatory proteins mainly secreted by activated polymorphonuclear neutrophils (PMNs). The underlying mechanisms for increased S100A8/A9 levels and their relation to the clinical phenotype have not been carefully investigated. We assessed S100A8/A9 and S100A12 levels in SLE patient sera in relation to disease activity, clinical phenotype, presence of anti-dsDNA antibodies and ability to promote phagocytosis of necrotic cells (NCs) by PMNs. Methods Serum levels of S100A8/A9 and S100A12 were measured by ELISA in paired samples of 100 SLE patients at time points of higher and lower disease activity. Serum-mediated phagocytosis of NCs by PMNs was analysed by flow cytometry. Clinical data were recorded at time points of blood sampling. Results Serum levels of S100A8/A9 and S100A12 were increased in SLE patients with high disease activity compared to paired samples at low disease activity ( p = 0.01 and p = 0.008, respectively). Elevated levels of S100A8/A9 were particularly seen in patients with anti-dsDNA antibodies ( p = 0.01) and glomerulonephritis before treatment ( p = 0.02). Immunosuppressive therapy was associated with a reduction of S100A8/A9 serum levels ( p = 0.002). The ability of serum to support phagocytosis of NCs by PMNs was related to increased S100A8/A9 levels ( p = 0.01). Conclusions Elevated serum levels of S100A8/A9 may be used to monitor disease activity and response to treatment in SLE patients, especially in patients with glomerulonephritis. S100A12 may be a marker of disease activity in SLE. Increased S100A8/A9 levels may reflect immune-pathological processes involving phagocytosis of immune complexes by PMNs.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1042-1042
Author(s):  
Christof Kaltenmeier ◽  
Ali Gawanbacht ◽  
Stefanie Lindner ◽  
Thamara Beyer ◽  
Georg Haerter ◽  
...  

Abstract Abstract 1042 Certain regulatory lymphocyte subpopulations including plasmacytoid dendritic cells and regulatory T cells secrete granzyme B (GrB), thereby suppressing T cell expansion. Recently, we found that B cells can also produce GrB and acquire regulatory potential in response to interleukin (IL-)21. Since HIV has been shown to be associated with elevated serum IL-21 levels, we hypothesized that GrB-expressing B cells may be induced during HIV infection. Here, we show that infection of CD4+ T cells with HIV 1 (NL4-3), but not mock infection, induces strong expression of IL-21 without upregulation of CD40 ligand. Importantly, we further demonstrate that such IL-21+CD40Llow T cells induce GrB in cocultured B cells in an IL-21-dependent fashion, rather than supporting their differentiation into plasma cells. In support of these findings, serum levels of both IL-21 and GrB are significantly higher in HIV-infected patients before HAART as compared to healthy controls. Up to 60% of freshly isolated B cells (36.2% ± 12.9%) from patients infected with HIV, but not B cells isolated from healthy individuals, express GrB. Of note, coculture of HIV-infected CD4+ T cells with GrB+ B cells result in GrB transfer, and strongly suppresses both, proliferation of T cells and viral replication as indicated by significantly reduced p24 levels in coculture supernatants. The observed effects are enhanced by IL-21, and reduced by GrB inhibition. In summary, we demonstrate that HIV infection induces IL-21 in CD4+ T cells, thereby indirectly triggering the development of GrB-secreting B cells with antiretroviral properties. GrB-secreting B cells may play a so far unappreciated role in decelerating HIV expansion, particularly in the early phase of infection. On the other hand, induction of GrB in HIV-specific B cells may interfere with their terminal differentiation into plasma cells, which may explain the lack of an efficient anti-HIV humoral immune response in HIV-infected patients. Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 29 (15_suppl) ◽  
pp. e11061-e11061
Author(s):  
J. M. Reuben ◽  
B. Arun ◽  
B. Lee ◽  
M. Galland ◽  
E. N. Cohen ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Francesco Rapisarda ◽  
Luca Zanoli ◽  
Grazia Portale ◽  
Salvo Scuto ◽  
Pietro Castellino

The IgG4-related disease is a fibroinflammatory disease characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum levels of IgG4. Idiopathic CD4 lymphocytopenia is a heterogenic and rare syndrome characterized by the detection of a persistent absolute CD4 T cells count <300 cells/mm3(or <20% of total T cells) in more than one occasion and no evidence of HIV infection in absence of immunodeficiency or therapy associated with depressed levels of CD4 T cells. We report the case of a 50-year-old man with a multiorgan IgG4-related disease presenting in a temporal association with a profound and symptomatic idiopathic CD4 lymphocytopenia. Both clinical pictures improved after steroid treatment. Idiopathic CD4 lymphocytopenia has been associated with a number of autoimmune conditions but, to the best of our knowledge, this is the first case in which an association with the IgG4-related disease is reported.


BioMedicine ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 24 ◽  
Author(s):  
Yasser Mohamed ◽  
Mohamed A. Basyony ◽  
Nabila I. El-Desouki ◽  
Walied S. Abdo ◽  
Mohammed A. El-Magd

Background/aim: Herein, we investigated the potential therapeutic effect of Melatonin (Mel) and/or mesenchymal stem cells (MSCs) on rat model of HCC. Materials and Methods: Female mature rats were divided into 5 groups (n = 10/group): normal (Nor), HCC group intraperitoneally injected with 200 mg/kg DEN, and 3 treated groups; HCC + Mel (Mel) group given Mel intraperitoneally 20 mg/kg, twice a week, HCC + MSCs (MSCs) group intravenously injected by 1 × 106 cells, and HCC + MSCs (Mel +MSCs) group. Results: Rats in HCC group showed most deteriorated effect in form of increased mortality and relative liver weight, elevated serum levels of ALT, AST, ALP, AFP and GGT in addition to increased pre-neoplastic nodules in liver tissues. Liver tissues of HCC group also exhibited lower level of apoptosis as indicated by decreased DNA fragmentation and expression of p53 caspase 9 and caspase 3 genes and increased PCNA immunoreactivity. Moreover, in this group the expression of IL6 and TGFβ1 genes was significantly upregulated. All these deleterious effects induced by DEN were reversed after administration of Mel and/ or MSCs with best improvement for the combined group (MSCs + Mel). Conclusions: These findings reveal a better therapeutic effect for MSCs when given with Mel and we attribute this beneficial effect, at least in part, to triggering apoptosis and targeting inflammation in HCC. Therefore, combined treatment with Mel and MSCs is recommended to enhance the therapeutic potential against HCC.


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