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- Dou, Diana R., et al.
(author)
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Xist ribonucleoproteins promote female sex-biased autoimmunity
- 2024
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In: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 187:3, s. 16-733
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Journal article (peer-reviewed)abstract
- Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long non-coding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex comprising numerous autoantigenic components is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multi-organ pathology in a pristane-induced lupus model than wild-type males. Xist expression in males reprogrammed T and B cell populations and chromatin states to more resemble wild-type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity.
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| 3. |
- Fauchez, Thomas J. J., et al.
(author)
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TRAPPIST Habitable Atmosphere Intercomparison (THAI) Workshop Report
- 2021
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In: The Planetary Science Journal. - : Institute of Physics Publishing (IOPP). - 2632-3338. ; 2:3
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Journal article (peer-reviewed)abstract
- The era of atmospheric characterization of terrestrial exoplanets is just around the corner. Modeling prior to observations is crucial in order to predict the observational challenges and to prepare for the data interpretation. This paper presents the report of the TRAPPIST Habitable Atmosphere Intercomparison workshop (2020 September 14-16). A review of the climate models and parameterizations of the atmospheric processes on terrestrial exoplanets, model advancements, and limitations, as well as direction for future model development, was discussed. We hope that this report will be used as a roadmap for future numerical simulations of exoplanet atmospheres and maintaining strong connections to the astronomical community.
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| 6. |
- Kalia, Lorraine V, et al.
(author)
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Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease.
- 2015
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In: JAMA Neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:1, s. 100-105
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Journal article (peer-reviewed)abstract
- Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD.
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| 8. |
- Langefeld, Carl D., et al.
(author)
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Transancestral mapping and genetic load in systemic lupus erythematosus
- 2017
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In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Journal article (peer-reviewed)abstract
- Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (similar to 50% of these regions have multiple independent associations); these include 24 novel SLE regions (P < 5 x 10(-8)), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.
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| 9. |
- Lu, R, et al.
(author)
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Genetic associations of LYN with systemic lupus erythematosus
- 2009
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In: Genes and Immunity. - : Springer Science and Business Media LLC. - 1466-4879 .- 1476-5470. ; 10:5, s. 397-403
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Journal article (peer-reviewed)abstract
- We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P=1.1 x 10(-4), odds ratio (OR)=0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5' untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total European-American population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P=1.5 x 10(-3), OR=0.75 (95% CI: 0.62-0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.
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