Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing‑remitting multiple sclerosis to natalizumab treatment

Fagone, Paolo; Mazzon, Emanuela; Mammana, Santa; Marco, Roberto Di; Spinasanta, Flaminia; Basile, Maria Sofia; Petralia, Maria Cristina; Bramantı, Placido; Nicoletti, Ferdinando; Mangano, Katia

doi:10.3892/mmr.2019.10283

Cited by 30 publications

(28 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also studied the possible diagnostic and prognostic value of TSPAN32 expression in PBMC of MS patients, on the course of the disease. The use of whole-genome expression databases has been largely exploited [25][26][27][28] for the characterization of pathogenic pathways and to identify therapeutic targets for a variety of disorders, including immunoinflammatory and autoimmune diseases [29][30][31][32][33][34][35][36], cancer [37][38][39], and has allowed dismantling pathogenetic pathways [40][41][42], along with the identification of novel tailored therapeutic targets [43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Tetraspanins are a conserved family of proteins involved in a number of biological processes. We have previously shown that Tetraspanin-32 (TSPAN32) is significantly downregulated upon activation of T helper cells via anti-CD3/CD28 stimulation. On the other hand, TSPAN32 is marginally modulated in activated Treg cells. A role for TSPAN32 in controlling the development of autoimmune responses is consistent with our observation that encephalitogenic T cells from myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice exhibit significantly lower levels of TSPAN32 as compared to naïve T cells. In the present study, by making use of ex vivo and in silico analysis, we aimed to better characterize the pathophysiological and diagnostic/prognostic role of TSPAN32 in T cell immunity and in multiple sclerosis (MS). We first show that TSPAN32 is significantly downregulated in memory T cells as compared to naïve T cells, and that it is further diminished upon ex vivo restimulation. Accordingly, following antigenic stimulation, myelin-specific memory T cells from MS patients showed significantly lower expression of TSPAN32 as compared to memory T cells from healthy donors (HD). The expression levels of TSPAN32 was significantly downregulated in peripheral blood mononuclear cells (PBMCs) from drug-naïve MS patients as compared to HD, irrespective of the disease state. Finally, when comparing patients undergoing early relapses in comparison to patients with longer stable disease, moderate but significantly lower levels of TSPAN32 expression were observed in PBMCs from the former group. Our data suggest a role for TSPAN32 in the immune responses underlying the pathophysiology of MS and represent a proof-of-concept for additional studies aiming at dissecting the eventual contribution of TSPAN32 in other autoimmune diseases and its possible use of TSPAN32 as a diagnostic factor and therapeutic target.

show abstract

Section: Discussionmentioning

confidence: 99%

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…pathways and therapeutic targets in several diseases, including cancer and autoimmune, fibrotic, neurodegenerative and infectious diseases (22,23,(54)(55)(56)(57)(58)(59). Presti et al (22) utilized RNA-seq data of 281 and 283 DNA-sequenced glioblastoma multiforme and low-grade glioma patients, respectively, to evaluate the expression levels of migration inhibitory factor (MIF) and related genes in glioma.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, KCNMA1 has been indicated as a therapeutic target in the early stages of CRC (60). For the study of multiple sclerosis (MS), Fagone et al (23) utilized microarray dataset analysis to obtain 45 genes that were differentially expressed between low and high responder CD4 + T cells. The identification of a specific gene signature for natalizumab responsiveness may provide a theoretical basis for suitable treatments for patients with MS, indicating the potential of microarray dataset analysis in improving the understanding of multiple disease types.…”

Section: Discussionmentioning

confidence: 99%

“…The application of microarray technology has enabled the extensive study of gene expression and has facilitated the research of disease susceptibility in favor of treating diseases at the molecular level. Several studies have indicated that microarray technology and in silico analysis have broad application in identifying pathogenetic mechanisms and novel diagnostic and therapeutic targets (22,23).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of circular RNA‑associated competing endogenous RNA network in breast cancer

Wang

Dong

et al. 2020

Oncol Lett

View full text Add to dashboard Cite

As the most common type of cancer in female patients, the morbidity and mortality rates of breast cancer (BC) are high, and its incidence is gradually increasing worldwide. However, the underlying molecular and genetic mechanisms involved in the etiopathogenesis of BC remain unclear. Circular RNAs (circRNAs) are a novel type of non-coding RNAs that have been verified to serve a crucial role in tumorigenesis. However, the majority of functions and mechanisms of circRNAs remain unknown. The present study identified 47 differentially expressed circRNAs in a dataset from Gene Expression Omnibus. Using the cancer-specific circRNA database, the potential microRNA (miRNA) response elements, RNA-binding proteins and open reading frames of the candidate circRNAs were predicted. Combing the predictions of miRNAs and target mRNAs, a competing endogenous RNA network was constructed, which may serve as the theoretical basis for further research. Furthermore, the analyses conducted using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways indicated that candidate circRNAs may serve a role in transcriptional regulation. Moreover, 20 BC tissue specimens and their paired adjacent normal tissue specimens were used to evaluate the expression levels of the screened circRNAs. Thus, the analyses of the raw microarray data conducted in the present study offer perspectives on the exploration of mechanisms associated with BC tumorigenesis with regard to the circRNA-miRNA-mRNA network.

show abstract

“…In the present study, we first analyzed the expression levels of IL37, SIGIRR, and IL18R1 in circulating immune cells from MS patients. In particular, we performed a DNA microarray analysis that represents a useful in silico tool for the better understanding of pathogenic pathways and the possible prediction of novel diagnostic therapeutic strategies, as it has been shown in a variety of clinical settings, such as autoimmune and immunoinflammatory diseases [38][39][40][41][42][43][44] and cancer [45][46][47][48][49][50][51], leading to the identification of novel therapeutic targets [52][53][54][55].…”

Section: Discussionmentioning

confidence: 99%

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

et al. 2019

Self Cite

View full text Add to dashboard Cite

We evaluated the in silico expression and circulating levels of interleukin (IL)37 in patients with different forms of multiple sclerosis (MS) and also upon treatment with different disease-modifying drugs. The combined interpretation of the resulting data strengthens and extends the current emerging concept that endogenous IL37 plays an important role in determining onset and progression of MS. The in silico analysis revealed that production of IL37 from cluster of differentiation (CD)4+ T cells from MS patients was reduced in vitro as compared to healthy controls. The analysis of the datasets also demonstrated that "higher" levels of IL37 production from PBMC entailed significant protection from MS relapses. In addition, the in vivo part of the study showed that IL37 was selectively augmented in the sera of MS patients during a relapse and that treatment with the high potency disease-modifying drug fingolimod significantly increased the frequency of patients with circulating blood levels of IL37 (6/9, 66%) as compared to patients receiving no treatment (n = 48) or platform therapy (n = 59) who had levels of IL37 below the limit of the sensitivity of the assay. This finding therefore anticipates that fingolimod may at least partially exert its beneficial effects in MS by upregulating the production of IL37.

show abstract

Identification of CD4+ T cell biomarkers for predicting the response of patients with relapsing‑remitting multiple sclerosis to natalizumab treatment

Cited by 30 publications

References 30 publications

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

Analysis of circular RNA‑associated competing endogenous RNA network in breast cancer

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

Contact Info

Product

Resources

About