Autoimmune lymphoproliferative syndrome: A disorder of immune dysregulation

Paskiewicz, Amy; Niu, Jianli; Chang, Christopher

doi:10.1016/j.autrev.2023.103442

Cited by 11 publications

(6 citation statements)

References 60 publications

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“…[9][10][11] SLE is a chronic immune disease that results from the formation of anti-DNA antibodies due to apoptotic clearance failure, leading to systemic inflammation in multiple tissues and systems. [10][11][12][13][14][15][16][17] A positive association between HSP and juvenile SLE was reported in a case-control study. The investigators identified particular risk factors based on information obtained from a systematic review, including childhood age of approximately 10 years, female sex, and anemia.…”

Section: Introductionmentioning

confidence: 82%

“…[12][13][14][15] The clinical manifestations of lymphoproliferative syndrome triggered by Fas malfunction encompass the existence of adenopathy, splenomegaly, and cytopenias in the pediatric population. 16 In the year 2013, research was carried out which revealed that Fas modifications led to a rise in the ratio of activation in a majority of cells where it is present; nevertheless, as mentioned earlier, it is reduced in both T lymphocytes and B lymphocytes. This implies that excessive lymphoid proliferation cannot be subjected to appropriate apoptosis and subsequent physiological clearance, leading to the perpetuation of lymphoproliferative syndrome over time and its progression into a chronic condition.…”

Section: Generation and Maintenance Of Lymphoproliferative Syndrome A...mentioning

confidence: 93%

“…This triggers the activation of the autoimmune system and the eventual production of doublestranded anti-DNA and antinuclear antibodies. 15 a commonality in the form of the deficiency in apoptotic clearance and lymphoproliferative syndrome, 10,12,16,17 from this point forward, we will clarify that the pathophysiological stages may potentially originate from the disturbance of a unique molecular pathway related to a gene that encodes a protein, specifically Fas (cell surface death receptor), which plays an essential role in apoptotic mechanisms.…”

Section: Fas and Apoptosismentioning

confidence: 99%

“…This proposed scheme offers a potential molecular relationship between HSP and systemic lupus erythematosus, but it should be noted that the downregulation of genes ENST00000378432, ENST00000571370, uc001kfc.1, and uc010qna.2 is not absolute, as alterations in p53 and TNF may also result in deregulation of Fas and apoptotic clearance. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]…”

Section: Figurementioning

confidence: 99%

“…[13][14][15] The apoptotic process being deficient in autoimmune diseases like SLE and HSP causes the perpetuation of the lymphoproliferative syndrome and the inability of the organism to eliminate it. [13][14][15][16][17] In the pathogenesis of systemic lupus erythematosus and IgA vasculitis there is a common pathway that is increased, the FAS/FAS ligand (FASL) pathway, however in both diseases there are mutations that interfere with its function. Fas and FasL are cell surface molecules that play an important role in apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Análisis del gen Fas como molécula causante del lupus eritematoso sistémico en pacientes con vasculitis IgA (púrpura de Henoch-Schönlein)

Doníz-Viveros,

Copca-Barrientos,

Hernández-Uribe

et al. 2024

Investigación en Discapacidad

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IgA vasculitis (HSP) and systemic lupus erythematosus (SLE) are both immune diseases that could be more interrelated than currently thought. HSP is an immune disease characterized by systemic small vessel vasculitis and mesangial deposits of immunoglobulin A, which ultimately leads to failure in apoptotic clearance and to the generation of a chronic lymphoproliferative syndrome. SLE is an immune disease characterized by chronic systemic inflammation that affects multiple tissues and systems, and its origin lies in the formation of double-stranded anti-DNA antibodies, which in turn are generated by failures in apoptotic clearance. HSP can be considered as a triggering factor for the development of systemic lupus erythematosus probably as the result of alterations in the apoptotic clearance that we think could be related to the inhibition of non-coding long-chain RNA genes (ENST00000378432, ENST00000571370, uc001kfc.1 y uc010qna.2) in patients with HSP, that in consequence alters Fas gene (CD95) track and the functions of the tumor necrosis factor family, that in turn inhibits the secretion of phosphatidylserine which ultimately generates a lymphoproliferative syndrome which possibly activates the double-stranded anti-DNA antibodies, the origin of SLE.

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Section: Introductionmentioning

confidence: 82%

Section: Generation and Maintenance Of Lymphoproliferative Syndrome A...mentioning

confidence: 93%

Section: Fas and Apoptosismentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Análisis del gen Fas como molécula causante del lupus eritematoso sistémico en pacientes con vasculitis IgA (púrpura de Henoch-Schönlein)

Doníz-Viveros,

Copca-Barrientos,

Hernández-Uribe

et al. 2024

Investigación en Discapacidad

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Outer Membrane Vesicles Derived From Fusobacterium nucleatum Trigger Periodontitis Through Host Overimmunity

Zhang,

Liu

et al. 2024

Advanced Science

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The virulent bacteria‐induced host immune response dominates the occurrence and progression of periodontal diseases because of the roles of individual virulence factors from these pathogens in the initiation and spread of inflammation. Outer membrane vesicles (OMVs) as a pathogenic entity have recently attracted great attention as messenger bridges between bacteria and host tissues. Herein, the novel role of OMVs derived from Fusobacterium nucleatum in the occurrence of periodontitis is dissected. In a rat periodontitis model, it is found that OMVs derived from F. nucleatum caused deterioration of periodontitis by enhancing inflammation of the periodontium and absorption of alveolar bone, which is almost equivalent to the effect of F. nucleatum itself. Furthermore, that OMVs can independently induce periodontitis is shown. The pathogenicity of OMVs is attributed to multiple pathogenic components identified by omics. After entering human periodontal ligament stem cells (hPDLSCs) by endocytosis, OMVs activated NLRP3 inflammasomes and impaired the mineralization of hPDLSCs through NF‐κB (p65) signaling, leading to the final injury of the periodontium and damage of alveolar bone in periodontitis. These results provide a new understanding of OMVs derived from pathogens and cues for the prevention of periodontitis.

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Phosphatidic Acid Promoting the Generation of Interleukin‐17A Producing Double‐Negative T Cells by Enhancing mTORC1 Signaling in Lupus

Li,

Tang,

Zheng

et al. 2024

Arthritis & Rheumatology

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ObjectivesTo investigate the role and intracellular regulatory mechanisms of double negative T (DNT) cells in the pathogenesis of systemic lupus erythematosus (SLE).MethodsDNT cells were assessed in murine models, SLE patients and controls using flow cytometry (FCM). DNT cells from either resiquimod (R848) or vehicle‐treated C57BL/6 (B6) mice were cultured with B cells from R848‐treated mice to explore functions. Differential mTOR pathway signaling in DNT cells measured using FCM and qPCR was validated by rapamycin inhibition. Candidate lipid metabolites detected using LC‐ESI‐MS/MS were functionally assessed in DNT cell cultures.ResultsDNT cells were markedly increased in both spontaneous and induced mouse lupus models and in SLE patients. Expanded DNT cells from R848‐treated B6 mice produced elevated IL‐17A and IgG with increased germinal center B (GCB) cells. Expansion of DNT cells associated with activation of mTORC1 pathway that both IL‐17A levels and the number of DNT cells exhibited dose‐dependent reduction with rapamycin treatment. Lipidomics studies revealed differential patterns of lipid metabolites in T cells of R848‐treated mice. Among candidate metabolites, elevated phosphatidic acid (PA) that was partially controlled by phospholipase D2, increased the expression of the mTORC1 downstream target p‐S6, and positively expanded IL‐17A‐producing DNT cells. Similarly, elevated proportions of circulating DNT cells in SLE patients correlated with disease activity and proteinuria, and IL‐17A secretion was elevated after in vitro PA stimulation.ConclusionsThe accumulation of PA in T cells could activate the mTORC1 pathway, promoting DNT cell expansion and IL‐17A secretion, resulting in GCB cell abnormalities in lupus.image

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Autoimmune lymphoproliferative syndrome: A disorder of immune dysregulation

Cited by 11 publications

References 60 publications

Análisis del gen Fas como molécula causante del lupus eritematoso sistémico en pacientes con vasculitis IgA (púrpura de Henoch-Schönlein)

Análisis del gen Fas como molécula causante del lupus eritematoso sistémico en pacientes con vasculitis IgA (púrpura de Henoch-Schönlein)

Outer Membrane Vesicles Derived From Fusobacterium nucleatum Trigger Periodontitis Through Host Overimmunity

Phosphatidic Acid Promoting the Generation of Interleukin‐17A Producing Double‐Negative T Cells by Enhancing mTORC1 Signaling in Lupus

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