Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using Whole-Exome Sequencing.

OBJECTIVE: Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole-exome sequencing (WES). METHODS: This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti-citrullinated protein antibody (ACPA-) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole-exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA- PR and ACPA+ PR. RESULTS: Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA-. We identified 8 novel loci (in the ACPA- PR group: ZNF503, RPS6KL1, HOMER3, HLA-DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA- PR group: HLA-DRB1*0803 and HLA-DQB1; in the ACPA+ PR group: HLA-DPA1*0401) that were associated with PR and that surpassed genome-wide significance (P < 5 × 10-8 ). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R2 < 0.025), whereas ACPA+ PR and ACPA- PR showed a moderate genetic correlation (0.38 < R2 < 0.8). CONCLUSION: This study demonstrated the distinct genetic background between ACPA- and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar.

Aboveground and Belowground Plant Traits Explain Latitudinal Patterns in Topsoil Fungal Communities From Tropical to Cold Temperate Forests.

Soil fungi predominate the forest topsoil microbial biomass and participate in biogeochemical cycling as decomposers, symbionts, and pathogens. They are intimately associated with plants but their interactions with aboveground and belowground plant traits are unclear. Here, we evaluated soil fungal communities and their relationships with leaf and root traits in nine forest ecosystems ranging from tropical to cold temperate along a 3,700-km transect in eastern China. Basidiomycota was the most abundant phylum, followed by Ascomycota, Zygomycota, Glomeromycota, and Chytridiomycota. There was no latitudinal trend in total, saprotrophic, and pathotrophic fungal richness. However, ectomycorrhizal fungal abundance and richness increased with latitude significantly and reached maxima in temperate forests. Saprotrophic and pathotrophic fungi were most abundant in tropical and subtropical forests and their abundance decreased with latitude. Spatial and climatic factors, soil properties, and plant traits collectively explained 45% of the variance in soil fungal richness. Specific root length and root biomass had the greatest direct effects on total fungal richness. Specific root length was the key determinant of saprotrophic and pathotrophic fungal richness while root phosphorus content was the main biotic factor determining ectomycorrhizal fungal richness. In contrast, spatial and climatic features, soil properties, total leaf nitrogen and phosphorus, specific root length, and root biomass collectively explained >60% of the variance in fungal community composition. Soil fungal richness and composition are strongly controlled by both aboveground and belowground plant traits. The findings of this study provide new evidence that plant traits predict soil fungal diversity distribution at the continental scale.

Soil properties and root traits jointly shape fine-scale spatial patterns of bacterial community and metabolic functions within a Korean pine forest.

Spatial heterogeneity of soil bacterial community depends on scales. The fine-scale spatial heterogeneity of bacterial community composition and functions remains unknown. We analyzed the main driving factors of fine-scale spatial patterns of soil bacterial community composition and carbon metabolic functions across a 30 m × 40 m plot within a Korean pine forest by combining Illumina 16S rRNA sequencing with Biolog Ecoplates based on 53 soil samples. Clear spatial patterns in bacterial community composition and metabolic functions were observed in the forest soil. The bacterial community composition and metabolic functions both showed distance-decay of similarity within a distance of meters. Structural equation model analysis revealed that environmental variables and geographic distance together explained 37.9% and 63.1% of community and metabolic functions, respectively. Among all environmental factors, soil organic carbon (SOC) and root biomass emerged as the most important drivers of the bacterial community structure. In contrast, soil pH explained the largest variance in metabolic functions. Root biomass explained the second-largest variance in soil bacterial community composition, but root traits made no difference in metabolic functions variance. These results allow us to better understand the mechanisms controlling belowground diversity and plant-microbe interactions in forest ecosystems.

Gilbert syndrome with systemic lupus erythematosus presenting with persistent unconjugated hyperbilirubinemia: A case report.

Gilbert syndrome (GS) is a hereditary unconjugated hyperbilirubinemia that results from mutations in the bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1) gene. To the best of our knowledge, there are currently no reports that focus on patients with systemic lupus erythematosus (SLE) coexisting with GS. The present study aimed to evaluate the clinical characteristics and genotype of UGT1A1 in a Chinese patient with SLE and GS. Complete medical records and laboratory data were reviewed for a patient with SLE referred to Ruijin Hospital (Shanghai, China) for treatment between March 2016 and January 2020. Genetic analysis of the UGT1A1 gene was performed by PCR amplification and Sanger sequencing. The serum total bilirubin and unconjugated bilirubin concentrations on admission were 96.2 and 86.8 µmol/l, respectively. The homozygous mutation c.1456T>G (p.Y486D) in exon 5 was detected in this patient. The patient had a good response to phenobarbital orally at a dose of 30 mg/day and a decrease in serum bilirubin was observed. Elevated unconjugated hyperbilirubinemia in SLE needs to be differentiated from other diseases, such as GS, which can be diagnosed by UGT1A1 genetic sequencing.

Biocrust as one of multiple stable states in global drylands.

Biocrusts cover ~30% of global drylands with a prominent role in the biogeochemical cycles. Theoretically, biocrusts, vascular plants, and bare soil can represent multiple stable states in drylands. However, no empirical evidence for the existence of a biocrust stable state has been reported. Here, using a global drylands dataset, we found that biocrusts form an alternative stable state (biocrust cover, ~80%; vascular cover, ≤10%) besides bare soil (both biocrust and vascular cover, ≤10%) and vascular plants (vascular cover, >50%; biocrust cover, ~5%). The pattern of multiple stable states associated with biocrusts differs from the classic fold bifurcation, and values of the aridity index in the range of 0 to 0.6 define a bistable region where multiple stable states coexist. This study empirically demonstrates the existence and thresholds of multiple stable states associated with biocrusts along climatic gradients and thus may greatly contribute to conservation and restoration of global drylands.