Immunogenetics in systemic lupus erythematosus: Transitioning from genetic associations to cellular effects

Lundtoft, Christian; Rönnblom, Lars

doi:10.1111/sji.12894

Cited by 19 publications

(16 citation statements)

References 105 publications

(147 reference statements)

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“…4 These conflicting findings confirm the previous notion that the genetic variants often exert their effect in "a celltype-specific and context-dependent manner." 19,35,36 Additional contributing factors could be due to the ethnicity, environmental, and geographical factors, as well as the variability in the sample size and methodology of the different studies.…”

Section: Discussionmentioning

confidence: 99%

“…Also, we encountered a single study that revealed a protective effect of the MIR17HG rs4284505*A allele with the development of breast carcinoma among the Australian population 4 . These conflicting findings confirm the previous notion that the genetic variants often exert their effect in “a cell‐type‐specific and context‐dependent manner.” 19,35,36 Additional contributing factors could be due to the ethnicity, environmental, and geographical factors, as well as the variability in the sample size and methodology of the different studies.…”

Section: Discussionmentioning

confidence: 99%

“…15 Our in silico analysis also revealed MIR17HG could target several immune-related genes involved in SLE development and progression (Figure 1). [16][17][18] As most genetic variants (ie, single-nucleotide polymorphisms [SNPs]) related to SLE risk were identified to be located in noncoding regions of the genome, 19 the study of MIR17HG cluster variants could enhance our understanding of its role in SLE pathogenesis. The most common SNP of this gene cluster is rs4284505 (G>A), which identified within the first intron of the MIR17HG.…”

Section: Introductionmentioning

confidence: 99%

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Association of microRNA 17 host gene variant (rs4284505) with susceptibility and severity of systemic lupus erythematosus

Abdel-Gawad

Shaheen

Babteen

et al. 2020

Immunity Inflam & Disease

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Objective MicroRNAs are large family clusters of small noncoding RNAs that implicated in genetic and epigenetic regulation of several immunological processes and pathways. As an epigenetic modifier, the microRNA 17‐92 cluster host gene (MIR17HG) has been shown to regulate the expression of genes involved in systemic lupus erythematosus (SLE) pathway. This study aimed to explore the association of MIR17HG (rs4284505; A>G) variant with SLE development and phenotype in a sample of the Eastern Mediterranean population. Methods A total of 326 participants (163 patients with SLE and 163 healthy controls) were enrolled in this study. The different genotypes of the MIR17HG (rs4284505) variant were characterized using the TaqMan real‐time polymerase chain reaction technique. Association with the available clinical and laboratory data, including the systemic lupus erythematosus disease activity index (SLEDAI), was also executed. Results The MIR17HG (rs4284505) variant showed a protective effect against developing SLE under heterozygote (A/G vs A/A; odds ratio [OR] = 0.10, 95% confidence interval [CI] = 0.05‐0.20, P < 0.001) and dominant (A/G+G/G vs A/A; OR = 0.39, 95% CI = 0.25‐0.61, P < .001) models. This association was consistent even after SLE stratified by lupus nephritis. In contrast, rs4284505 (G/G) genotype conferred increased susceptibility to SLE (G/G vs A/A+A/G; OR = 2.15, 95% CI = 1.31‐3.53, P = .002). Moreover, the rs4284505 variant showed a statistically significant association with mucocutaneous lesions and SLEDAI scores (all P < .05). Conclusion This study is the first one to explore that the MIR17HG rs4284505 is associated with SLE risk; (A/G) genotype conferred a protective effect, while the (G/G) genotype showed increased susceptibility to SLE and association with the disease severity in the study population.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of microRNA 17 host gene variant (rs4284505) with susceptibility and severity of systemic lupus erythematosus

Abdel-Gawad

Shaheen

Babteen

et al. 2020

Immunity Inflam & Disease

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“…Ernestina Belt, MD 1 Ernestina.Belt@ajch.ae ORCID-ID 0000-0002-5044-5599 Nidheesh Chencheri, MD 1 drnidheesh@gmail.com ORCID-ID 0000-0002-9142-708X…”

Section: Authors' Informationmentioning

confidence: 99%

“…Its etiology involves genetic, epigenetic and environmental factors. (1) The initial diagnosis of SLE can pose diagnostic challenges due to its variable presentation. Reported incidence rates of neuropsychiatric symptoms among children with SLE vary between 14% and 75%.…”

Section: Introductionmentioning

confidence: 99%

Guillain Barré Syndrome as Primary Presentation of Systemic Lupus Erythematosus (SLE-GBS) in a Teenage Girl: A Case Report

Beshir

Belt

Chencheri

et al. 2021

Preprint

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Background: Peripheral nervous system (PNS) involvement, including Guillain Barré Syndrome (GBS), accounts for fewer than 10% of SLE cases with neuropsychiatric manifestations. GBS as the presenting, major manifestation of pediatric SLE is extremely rare, and the best treatment approach is unknown. Case presentation: A 14-year-old, previously healthy female Emirati teenager presented with a classic picture of GBS with ascending, progressive bilateral muscle weakness leading to respiratory insufficiency within five weeks of symptom onset, associated with typical protein-cell dissociation in cerebro-spinal fluid and nerve root enhancement demonstrated by spinal MRI. Subsequently, elevated anti-dsDNA and anti-Smith/RNP and anti-SS-A and -B antibody concentrations were detected in serum, suggestive of SLE. GBS treatment was initiated with IVIG and methylprednisolone pulses, with minimal improvement. The patient required endotracheal intubation and ventilation, followed by a second course of IVIG, rituximab, and eventually plasma exchange (PLEX) therapy. The diagnosis of lupus-associated GBS was corroborated by a kidney biopsy demonstrating lupus nephritis WHO class II with “full house” immunofluorescence pattern. After 14 PLEX sessions, her muscle strength and respiratory efforts had improved substantially. Treatment was completed with two more rituximab infusions, followed by mycophenolate mofetil, in addition to HCQ and tapering doses of oral prednisolone. Five weeks after the last PLEX treatment, she had regained her usual strength and achieved full, sustained recovery from GBS. While she continued to demonstrate moderate anti-dsDNA antibodies and high-level anti-Smith and Sjogren antibodies, C3, C4 and urine readings quickly normalized with no other manifestations of lupus or lupus nephritis 11 months after the initial assessment. At this time she was maintained with hydroxychloroquine, with ongoing depletion of circulating B cells. To our knowledge, this is only the third pediatric patient reported with SLE-GBS.Conclusions: We report severe GBS as the first, dominant manifestation of pediatric SLE. Our case and a review of the literature reveal that cconventional GBS therapy may not be adequate to treat this rare lupus presentation. SLE should be included in the differential diagnosis of GBS. Importantly, treatment experiences and outcomes of such cases need be reported to inform future treatment recommendations.

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Development of multi-omics approach in autoimmune diseases

Choi

Fritzler

Mähler

2021

Precision Medicine and Artificial Intelligence

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Immunogenetics in systemic lupus erythematosus: Transitioning from genetic associations to cellular effects

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 19 publications

References 105 publications

Association of microRNA 17 host gene variant (rs4284505) with susceptibility and severity of systemic lupus erythematosus

Association of microRNA 17 host gene variant (rs4284505) with susceptibility and severity of systemic lupus erythematosus

Guillain Barré Syndrome as Primary Presentation of Systemic Lupus Erythematosus (SLE-GBS) in a Teenage Girl: A Case Report

Development of multi-omics approach in autoimmune diseases

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