Pathogenesis of systemic lupus erythematosus

Mok, Chi Chiu; Lau, Chak Sing

doi:10.1136/jcp.56.7.481

Cited by 724 publications

(577 citation statements)

References 127 publications

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“…1 When we looked for the risk/protective HLA haplotypes extended with MICA and PRL alleles we did not find any significant differences between SLE and controls. However, we noticed a trend: the haplotype DRB1*03-DQB1*0201-MICA-A5.1 was more common in SLE patients 72.7% than in controls 20.0%, p u =0.002 (OR 11.11), but the combination of DRB1*03-DQB1*0201 and MICA-A4 and MICA-A6 seems to occur rarely in SLE than healthy subjects, 5.5% and 33.3%, p u =0.002 (OR 0.12) and 1.8% and 33.3%, p u =0.001 (OR 0.04), respectively.…”

Section: Mica Transmembrane Microsatellite Polymorphism Exon 5 Analysismentioning

confidence: 78%

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HLA class II, MICA and PRL gene polymorphisms: the common contribution to the systemic lupus erythematosus development in Czech population

et al. 2010

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ObjectiveThe genetic components contribute to the Systemic lupus erythematosus development. This study for the first time determined the distribution of the polymorphisms and linkage disequilibrium in HLA class II, MICA and PRL gene among patients suffering from SLE and healthy Czech individuals. Patients and Methods DNA ConclusionHLA class II-MICA combinations may increase/decrease a risk for SLE development.Multiple studies focusing on the ethnical differences as well as genetic-epigenetic relationships are necessary for better understanding SLE pathogenesis.

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Section: Mica Transmembrane Microsatellite Polymorphism Exon 5 Analysismentioning

confidence: 78%

“…The pathogenesis of this illness has not been still clearly elucidated. However, complex changes during the network of the immune response may result in production of the pathogenic autoantibodies and organ damage by the immune complexes consumption [1].…”

Section: Introductionmentioning

confidence: 99%

HLA class II, MICA and PRL gene polymorphisms: the common contribution to the systemic lupus erythematosus development in Czech population

et al. 2010

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“…SLE is a multiorgan system autoimmune disease with numerous immunological and clinical manifestations [1]. It is characterized by a large amount of circulating autoantibodies (autoAb) with diverse specificities as a result of abnormal activation of autoreactive B-and T-helper lymphocytes [2,3].…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

Henriques¹,

Inês

Carvalheiro³

et al. 2011

Rheumatol Int

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With the purpose of contributing to a better knowledge of the APCs functional activity in SLE, we evaluated the distribution and functional ability to produce pro-inflammatory cytokines (TNF-a, IL-1b, IL-6 and IL-12) of peripheral blood (PB) monocytes and DC (tDC), particularly myeloid (mDC) and CD14 -/low CD16 ? DC subpopulations comparing them with those obtained from healthy individuals. The study was performed in 34 SLE patients with diverse disease activity scores (SLEDAI) and 13 healthy age-and sex-matched controls (NC). Our results show an overall decrease in absolute number and relative frequency of tDC in SLE patients with active disease when compared to those with inactive disease and NC, although this decrease did not seem to have an effect on the distribution of PB DC subsets. The monocytes number in SLE patients was similar to those found in NC, whereas a higher frequency of monocytes producing cytokines as well as the amount of each cytokine per cell found without stimulation was particularly observed in those patients with active disease. After stimulation, we observed a higher frequency of IL-12-producing monocytes in active SLE patients. On the other hand, we found among DCs higher frequencies of cytokine-producing CD14 -/low CD16 ? DCs and a higher amount of cytokines produced per cell, particularly in active disease. These findings support an increased production of inflammatory cytokines by APCs in active SLE, mostly associated with alterations in CD14 -/low CD16 ? DC subset homeostasis that might contribute to explain the dynamic role of these cells in disease pathogenesis.

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“…3 For all these diseases, inflammatory mechanisms have been implicated. [4][5][6][7][8][9] In addition, inflammation has also been postulated as explanation for the simultaneous occurrence of these conditions.…”

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confidence: 99%

Heritability estimates of innate immunity: an extended twin study

et al. 2005

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Cytokines are key players in numerous inflammatory processes. Demonstration of a heritable component in the variation of cytokine production would indicate that simultaneous occurrence of conditions might be caused by a heritable inflammatory characteristic. We applied an extended twin study approach to assess heritability estimates of interleukin (IL)-1b, IL-1ra, IL-10, IL-6, and TNF-a production capacity after ex vivo stimulation with lipopolysaccharide. Cytokine production capacity was assessed in 42 monozygotic pairs, 52 dizygotic pairs, one trizygotic triplet, 33 single twins, and 83 additional siblings. Heritability estimates were derived from variance decomposition models using maximum likelihood estimation. For all cytokines, over 50% of the variance was genetically determined. IL-1ra and TNF-a had the lowest heritability estimate of 53%.Estimates for IL-6 and IL-10 were 57 and 62%, respectively. IL-1b had the highest estimate of 86%. We conclude that the production of cytokines is under tight genetic control.

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Pathogenesis of systemic lupus erythematosus

Cited by 724 publications

References 127 publications

HLA class II, MICA and PRL gene polymorphisms: the common contribution to the systemic lupus erythematosus development in Czech population

HLA class II, MICA and PRL gene polymorphisms: the common contribution to the systemic lupus erythematosus development in Czech population

Functional characterization of peripheral blood dendritic cells and monocytes in systemic lupus erythematosus

Heritability estimates of innate immunity: an extended twin study

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