Pathogenetic Mechanisms Implicated in Sjögren’s Syndrome Lymphomagenesis: A Review of the Literature

Stergiou, Ioanna Ε.; Poulaki, Aikaterini; Voulgarelis, Michael

doi:10.3390/jcm9123794

Cited by 23 publications

(17 citation statements)

References 135 publications

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“…Examples of two cytokines are a proliferation-inducing ligand (APRIL) and B cell-activating factor (BAFF), which are members of the tumor necrosis factor family and play a key role in B cells and autoimmunity. Both cytokines are secreted by eosinophils and/or macrophages and stimulate MALT lymphoma cells[ 52 - 54 ]. Both the CD40/CD40L interaction and APRIL and/or BAFF signaling cause the activation of important downstream signaling pathways, e.g.…”

Section: Chronic Inflammation Shapes the Microenvironment And Thereby Plays A Key Role In Malt Lymphomagenesismentioning

confidence: 99%

“…As reported in section 3, in MALT lymphoma cells, the NF-κB pathway is strongly activated by genetic alterations[ 18 , 76 , 77 ] or by interaction with activated immune cells via the CD40/CD40L[ 52 - 54 , 56 ] and/or APRIL axes[ 77 - 79 ].…”

Section: Tumor Microenvironment-targeting Therapiesmentioning

confidence: 99%

“…Moreover, bortezomib enacts immunostimulatory effects by activating tumor-infiltrating CD8+ T cells[ 61 , 62 ]. Taken together, these findings suggest that the anti-lymphoma effects of bortezomib are mediated by NF-κB inhibition and by reversal of the observed T cell malfunction[ 52 - 54 ].…”

Section: Tumor Microenvironment-targeting Therapiesmentioning

confidence: 99%

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Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas

Uhl¹,

Prochazka²,

Fechter³

et al. 2022

WJGO

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Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphomas of mucosa-associated lymphoid tissue (MALT), also known as MALT lymphomas. These arise at a wide range of different extranodal sites, with most cases affecting the stomach, the lung, the ocular adnexa and the thyroid. The small intestine is involved in a lower percentage of cases. Lymphoma growth in the early stages is associated with long-lasting chronic inflammation provoked by bacterial infections ( e.g ., Helicobacter pylori or Chlamydia psittaci infections) or autoimmune conditions ( e.g ., Sjögren’s syndrome or Hashimoto thyroiditis). While these inflammatory processes trigger lymphoma cell proliferation and/or survival, they also shape the microenvironment. Thus, activated immune cells are actively recruited to the lymphoma, resulting in either direct lymphoma cell stimulation via surface receptor interactions and/or indirect lymphoma cell stimulation via secretion of soluble factors like cytokines. In addition, chronic inflammatory conditions cause the acquisition of genetic alterations resulting in autonomous lymphoma cell growth. Recently, novel agents targeting the microenvironment have been developed and clinically tested in MALT lymphomas as well as other lymphoid malignancies. In this review, we aim to describe the composition of the microenvironment of MALT lymphoma, the interaction of activated immune cells with lymphoma cells and novel therapeutic approaches in MALT lymphomas using immunomodulatory and/or microenvironment-targeting agents.

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Section: Chronic Inflammation Shapes the Microenvironment And Thereby Plays A Key Role In Malt Lymphomagenesismentioning

confidence: 99%

Section: Tumor Microenvironment-targeting Therapiesmentioning

confidence: 99%

See 1 more Smart Citation

Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas

Uhl¹,

Prochazka²,

Fechter³

et al. 2022

WJGO

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“…These cells are able to produce type I IFNs ( 31 , 32 ), and, together with SGECs, B cell activating factor (BAFF) ( 33 ). The latter cytokine, along with IL-6, plays a fundamental role in B cell proliferation and survival, and, in the later phase of the disease, may induce lymphomagenesis ( 34 ). Type I IFNs act by transcription of IFN-related genes which contribute to the autocrine and paracrine maintenance of the inflammatory state ( 35 ).…”

Section: Summary On the Pathogenesis Of Pssmentioning

confidence: 99%

Management of Sjögren's Syndrome: Present Issues and Future Perspectives

et al. 2021

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In view of the new possibilities for the treatment of primary Sjögren's syndrome (pSS) given by the availability of new biotechnological agents targeting the various molecular and cellular actors of the pathological process of the disease, classification criteria aimed at selecting patients to be enrolled in therapeutic trials, and validated outcome measures to be used as response criteria to these new therapies, have been developed and validated in the last decades. Unfortunately, the therapeutic trials so far completed with these new treatments have yielded unsatisfactory or only partially positive results. The main issues that have been evoked to justify the poor results of the new therapeutic attempts are: (i) the extreme variability of the disease phenotypes of the patients enrolled in the trials, which are dependent on different underlying patterns of biological mechanisms, (ii) the fact that the disease has a long indolent course, and that most of the enrolled patients might already have irreversible clinical features. The advances in the research of new disease biomarkers that can better distinguish the different clinical phenotypes of patients and diagnose the disease in an earlier phase are also discussed.

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“…Disease hallmarks include B-cell hyperactivity, oversecretion of serum autoantibodies such as anti-Ro/SSA, anti-La/SSB, and rheumatoid factor (RF), as well as the activation of type I and type II interferon (IFN) pathways [4][5][6][7]. The most severe disease complication is the development of non-Hodgkin's lymphoma (NHL), which occurs in 5-10% of primary SS patients and represents the leading cause of disease-related mortality [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

+3179G/A Insulin-Like Growth Factor-1 Receptor Polymorphism: A Novel Susceptibility Contributor in Anti-Ro/SSA Positive Patients with Sjögren’s Syndrome: Potential Clinical and Pathogenetic Implications

Skarlis

Marketos

Nezos

et al. 2021

JCM

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Background: Alterations of the insulin-like growth factor (IGF) pathway along with genetic variations of the IGF1 receptor (IGF1R) gene have been linked to the development of systemic autoimmunity, possibly through apoptosis induction. This study aims to investigate whether genetic variations of the IGF1R contribute to Sjögren’s syndrome (SS) pathogenesis and explores potential functional implications. Methods: DNA extracted from whole peripheral blood derived from 277 primary SS patients, complicated or not by lymphoma, and 337 Healthy controls (HC) was genotyped for the rs2229765 IGF1R polymorphism using the RFLP-PCR assay. Gene expression of IGF1R and IGF1 isoforms, caspases 1, 4, and 5, and inflammasome components NLRP3, ASC, IL1β, IL18, IL33, IGFBP3, and IGFBP6 were quantitated by RT-PCR in total RNA extracted from minor salivary gland biopsies (MSGs) of 50 SS patients and 13 sicca controls (SCs). In addition, IGF1R immunohistochemical (IHC) expression was assessed in formalin-fixed, paraffin-embedded MSG tissue sections derived from 10 SS patients and 5 SCs. Results: The prevalence of the A/A genotype of the rs2229765 IGF1R polymorphism was significantly higher in the anti-Ro/SSA positive SS population compared to healthy controls (24.8% vs. 10.7%, p = 0.001). Moreover, IGF1Rs at both mRNA and protein levels were reduced in SS-derived MSGs compared to SCs and were negatively associated with caspase 1 transcripts. The latter were positively correlated with NLRP3, ASC, and IL1β at the salivary gland tissue level. IGF1R expression in peripheral blood was negatively correlated with ESR and IgG serum levels and positively correlated with urine-specific gravity values. Conclusions: The rs2229765 IGF1R variant confers increased susceptibility for seropositive primary SS. Dampened IGF1R mRNA and protein expression in salivary gland tissues could be related to increased apoptosis and subsequently to the activation of inflammasome pathways.

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Pathogenetic Mechanisms Implicated in Sjögren’s Syndrome Lymphomagenesis: A Review of the Literature

Cited by 23 publications

References 135 publications

Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas

Impact of the microenvironment on the pathogenesis of mucosa-associated lymphoid tissue lymphomas

Management of Sjögren's Syndrome: Present Issues and Future Perspectives

+3179G/A Insulin-Like Growth Factor-1 Receptor Polymorphism: A Novel Susceptibility Contributor in Anti-Ro/SSA Positive Patients with Sjögren’s Syndrome: Potential Clinical and Pathogenetic Implications

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