Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

Crampton, Steve P.; Morawski, Peter A.; Bolland, Silvia

doi:10.1242/dmm.016451

Cited by 69 publications

(56 citation statements)

References 235 publications

(274 reference statements)

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“…and Sjögren's syndrome [MIM (270150)] are two clinically related systemic autoimmune diseases (SADs) with a complex cause [1]. The complexity resides in the combination of environmental and genetic factors in the initiation and progression toward disease development that occurs with time.…”

Section: Systemic Lupus Erythematosus [Sle Mim (152700)]mentioning

confidence: 99%

“…The loss of tolerance in the immune system leads to the presence of autoantibodies and the deposition of immune complexes in various tissues, causing a great diversity of symptoms [2]. The cause of the disease is complex and both environmental and genetic factors are involved [1]. The genes are important in SLE susceptibility as shown in family studies [3][4][5] and the concordance rate between twins.…”

Section: Genetics Of Systemic Lupus Erythematosusmentioning

confidence: 99%

See 1 more Smart Citation

Genetics of systemic lupus erythematosus and Sjögren's syndrome: an update

Teruel

Alarcón‐Riquelme

2016

Current Opinion in Rheumatology

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SLE and Sjögren's syndrome are two closely related systemic autoimmune diseases that share multiple clinical and molecular aspects, including a significant number of susceptibility genes. Several genome-wide association studies were recently published in different populations that provide a better picture of their molecular mechanisms. It is becoming clear that their genetic architecture is quite well established, but more information is required on expression quantitative trait loci, epigenetic genome-wide analyses, gene × gene interactions and the role of rare variants.

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Section: Systemic Lupus Erythematosus [Sle Mim (152700)]mentioning

confidence: 99%

Section: Genetics Of Systemic Lupus Erythematosusmentioning

confidence: 99%

Genetics of systemic lupus erythematosus and Sjögren's syndrome: an update

Teruel

Alarcón‐Riquelme

2016

Current Opinion in Rheumatology

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“…Moreover, this disease is often observed in women of child-bearing age. Pregnancy promotes disease development [3]. Delayed therapy to pregnant patients with SLE may cause abortion, pregnancy-induced hypertension syndrome, renal damage, and other complications.…”

Section: Introductionmentioning

confidence: 99%

Feasibility of hydroxychloroquine adjuvant therapy in pregnant women with systemic lupus erythematosus

Liu¹,

Liu²,

Zhou³

2018

biomedicalresearch

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Objective: This study aims to investigate the clinical effects of hydroxychloroquine adjuvant therapy in pregnant women with Systemic Lupus Erythematosus (SLE). Methods: A total of 78 pregnant women with SLE from February 2016 to August 2017 were recruited and divided into two groups, control (n=39) and observation (n=39), by using a random number table. The observation group received hydroxychloroquine adjuvant therapy, whereas the control group received conventional symptomatic treatment. The lupus activity during pregnancy, term birth rate, pregnancy and fetus outcomes, new-born Apgar score, and neonatal weight of the two groups were compared. Results: The occurrence rate of lupus during pregnancy in the observation group was 25.64%, which was significantly lower than that of the control group (51.28%) (P<0.05). The observation group achieved significantly higher term birth rate (84.62%) than the control group (58.97%) (P<0.05). The occurrence rates of bad pregnancy and fetus outcomes of the observation and control groups were 17.95% and 44.44%, respectively, which showed a significant difference (P<0.05). The new-born Apgar score and neonatal weight of the observation group were 9.61 ± 0.25 and 2.78 ± 0.56 kg, whereas those of the control group were 8.10 ± 0.31 and 2.47 ± 0.58 kg, showing a significant difference (P<0.05). Conclusions: Hydroxychloroquine adjuvant therapy exerts outstanding clinical effects to pregnant patients with SLE. This therapy not only improves pregnancy outcome but also reduces the occurrence of lupus. This method has a very high clinical application value and is worthy of further clinical research and applications.

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“…Several mouse models, including the Sle1Sle3 mouse model, have been extensively used for the study of lupus pathogenesis [18–24]. Sle1Sle3 mice carry the bicongenic Sle1 and Sle3 loci that confer susceptability to lupus development [22].…”

Section: Introductionmentioning

confidence: 99%

PKK deficiency in B cells prevents lupus development in Sle lupus mice

et al. 2017

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B- lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment.

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Linking susceptibility genes and pathogenesis mechanisms using mouse models of systemic lupus erythematosus

Cited by 69 publications

References 235 publications

Genetics of systemic lupus erythematosus and Sjögren's syndrome: an update

Genetics of systemic lupus erythematosus and Sjögren's syndrome: an update

Feasibility of hydroxychloroquine adjuvant therapy in pregnant women with systemic lupus erythematosus

PKK deficiency in B cells prevents lupus development in Sle lupus mice

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