Biology subjects

Liu, H.

Publications and source records attributed to Liu, H..

At least 1,009 records · Page 56Linked to original sources

bioRxiv2018

PLOS ONETitle - Optimization of the flash extraction of flavonoids from the leaves of Salix babylonica using the response surface method and an evaluation of the leaves high antioxidant activity

Many biological activities of Salix babylonica leaves are attributed to the plants high total flavonoid content. Flash extraction has the advantages of high efficiency and maximum retention of the active ingredient. In this study, flash extraction was used to extract the total flavonoids, and a Box-Behnken design was used to optimize the extraction conditions for the first time. The effects of four independent variables, including ethanol concentration, extraction voltage, time, and ratio of liquid to material on flavonoid yield, was determined, and the optimal conditions for flavonoid extraction were evaluated using response surface methodology. Statistical analyses showed that the linear and quadratic terms of these four variables had significant effects. The fitted second-order model revealed that the optimal conditions consisted of an ethanol concentration of 67.91%, extraction time of 87 s, extraction voltage of 116 V and ratio of liquid to material of 42.79. Under the optimum conditions, the experimental value of 66.40{+/-}0.80% nearly coincided with that predicted by the model. In the ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) assays, the extracts showed significant antioxidant and scavenging capacity for free radicals, respectively. This study helps to better exploit the resources of Salix babylonica leaves and provides new insights for effective extraction of flavonoids.

pharmacology and toxicology↗

bioRxiv2018

Gut Microbiota in male patients with chronic traumatic complete spinal cord injury

This study examined the diversity and structure of gut microbiota in healthy adults and chronic traumatic complete spinal cord injury (SCI) patients, documented neurogenic bowel management of SCI patients. The V3-V4 region of 16S rRNA gene from DNA of 91 fecal samples of 48 healthy and 43 diseased subjects was amplified and sequenced. There was difference in gut microbiota between healthy adult males and females. Neurogenic bowel dysfunction (NBD) was common in patients with chronic traumatic complete SCI, patients with quadriplegia have longer time to defecate than paraplegic patients, with higher NBD scores and heavier neurogenic bowel symptoms. Gut microbiota dysbiosis existed in SCI patients. The abundance of Veillonellaceae and Prevotellaceae increased while Bacteroidaceae and Bacteroides decreased in SCI group. The abundance of Bacteroidaceae, Bacteroides in quadriplegia group and Acidaminococcaceae, Blautia in paraplegia group were significant high than the health male group. Serum biomarkers GLU, HDL, CR and NBD symptoms defecation time, COURSE had significant correlation with microbial community structure. This study presents a comprehensive landscape of gut microbiota in adult male patients with chronic traumatic complete SCI and documents their neurogenic bowel management. The gut microbiota dysbiosis of SCI patients was correlation with serum biomarkers and NBD symptoms.\n\nIMPORTANCENeurogenic bowel dysfunction is a major physical and psychological problem in patients with spinal cord injury, which can seriously affect the quality life of them. Gut dysbiosis are highly likely to occur in spinal cord injury patients There are few studies on intestinal microecology after spinal cord injury, and the clinical studies are fewer. It is importance to document their neurogenic bowel management and present a landscape of gut microbiota in them. We found the gut microbiota dysbiosis of spinal cord injury patients was correlation with serum biomarkers and neurogenic bowel dysfunction symptoms. These results may have implications in the next study about metagenomics and precision treatment of neurogenic bowel dysfunction in spinal cord injury patients.

neuroscience↗

bioRxiv2018

Molecular Subtyping reveals Immune Alterations associated with Progression of Bronchial Premalignant Lesions

Bronchial premalignant lesions (PMLs) are precursors of lung squamous cell carcinoma, but have variable outcome, and we lack tools to identify and treat PMLs at highest risk for progression to invasive cancer. Profiling endobronchial biopsies of PMLs obtained from high-risk smokers by RNA-Seq identified four PML subtypes with differences in epithelial and immune processes. One molecular subtype (Proliferative) is enriched with dysplastic lesions and exhibits up-regulation of metabolic and cell cycle pathways and down-regulation of ciliary processes. RNA-Seq profiles from normal-appearing uninvolved large airway brushings could identify subjects with Proliferative lesions with high specificity. Expression of interferon signaling and antigen processing/presentation pathways are decreased in progressive/persistent Proliferative lesions and immunofluorescence indicates a depletion of innate and adaptive immune cells in these lesions. Molecular biomarkers measured in PMLs or the uninvolved airway can enhance histopathological grading and suggests that immunoprevention strategies may be effective in intercepting the progression of PMLs to lung cancer.

cancer biology↗

bioRxiv2018

A novel function of Galactomyces candidum in highly efficient ammonia nitrogen removal from low C:N wastewater

A strain of bacteria that demonstrated efficient nitrogen removal potential under low C:N conditions was screened from landfill leachate. The strain was identified as Galactomyces candidum by ITS sequencing, and growth density and removal of ammonia nitrogen were assessed after 24 h of incubation. The results showed that the optimum ammonia nitrogen reduction conditions for G. candidum was at pH 8.0 and 30 {degrees}C, with a C:N ratio of 1.5:1; the highest rate of ammonia nitrogen removal was 93.1%. This novel function of G. candidum offers great potential in the removal of ammonia nitrogen from sewage, especially in low C:N wastewater. Our study provides a new theoretical basis for the industrial application of bacteria in the biochemical treatment of wastewater and reduces environmental pollution.\n\nA novel function and potential of Galamyces candidum in the removal of ammonia nitrogen from wastewater treatment was found, which provides a theoretical basis for the treatment of ammonia in wastewater.

microbiology↗

bioRxiv2018

Defining the toxicity limits on microbial range in a metal-contaminated aquifer

In extreme environments, toxic compounds restrict which microorganisms persist. However, in complex mixtures of inhibitory compounds, it is challenging to determine which specific compounds cause changes in abundance and prevent some microorganisms from growing. We focused on a contaminated aquifer in Oak Ridge, Tennessee, U.S.A. that has low pH and high concentrations of uranium, nitrate and many other inorganic ions. In the most contaminated wells, the microbial community is enriched in the Rhodanobacter genus. Rhodanobacter relative abundance is positively correlated with low pH and high concentrations of U, Mn, Al, Cd, Zn, Ni, Co, Ca, NO3-, Mg, Cl, SO42-, Sr, K and Ba and we sought to determine which of these correlated parameters are selective pressures that favor the growth of Rhodanobacter over other taxa. Using high-throughput cultivation, we determined that of the ions correlated high Rhodanobacter abundance, only low pH and high U, Mn, Al, Cd, Zn, Co and Ni (a) are selectively inhibitory of a sensitive Pseudomonas isolate from a background well versus a representative resistant Rhodanobacter isolate from a contaminated well, and (b) reach toxic concentrations in the most contaminated wells that can inhibit the sensitive Pseudomonas isolate. We prepared mixtures of inorganic ions representative of the most contaminated wells and verified that few other isolates aside from Rhodanobacter can tolerate these 8 parameters. These results clarify which toxic inorganic ions are causal factors that impact the microbial community at this field site and are not merely correlated with taxonomic shifts.

microbiology↗

bioRxiv2018

Heterodimerization of UNC-13/RIM regulates synaptic vesicle release probability but not priming

UNC-13 proteins play an essential role in synaptic transmission by recruiting synaptic vesicles (SVs) to become available for release, which is termed SV priming. Here we show that the C2A domain of UNC-13L, like the corresponding domain in mammalian Munc13-1, displays two conserved binding modes: forming C2A/C2A homodimers, or forming a heterodimer with the zinc finger domain of UNC-10/RIM (C2A/RIM). Functional analysis revealed that UNC-13Ls C2A promotes synaptic transmission by regulating a post-priming process. Stimulus-evoked release but not SV priming, was impaired in unc-10 mutants deficient for C2A/RIM heterodimerization, leading to decreased release probability. Disrupting C2A/C2A homodimerization in UNC-13L-rescued animals had no effect on synaptic transmission, but fully restored the evoked release and the release probability of unc-10/RIM mutants deficient for C2A/RIM heterodimerization. Thus, our results support the model that RIM binding C2A releases UNC-13L from an autoinhibitory homodimeric complex to become fusion-competent by functioning as a switch only.

neuroscience↗

bioRxiv2018

Identification, Genotyping, and Pathogenicity of Trichosporon spp. Isolated from Giant Pandas

Trichosporon is the dominant genus of epidermal fungi in giant pandas and causes local and deep infections. To provide the information needed for the diagnosis and treatment of trichosporosis in giant pandas, the sequence of ITS, D1/D2, and IGS1 loci in 29 isolates of Trichosporon spp. which isolated from the body surface of giant pandas were combination to investigate interspecies identification and genotype. Morphological development was examined via slide culture. Additionally, mice were infected by skin inunction, intraperitoneal injection, and subcutaneous injection for evaluation of pathogenicity. The twenty-nine isolates of Trichosporon spp. were identified as belonging to 11 species, and Trichosporon jirovecii and T. asteroides were the commonest species. Four strains of T. laibachii and one strain of T. moniliiforme were found to be of novel genotypes, and T. jirovecii was identified to be genotype 1. T. asteroides had the same genotype which involved in disseminated trichosporosis. The morphological development processes of the Trichosporon spp. were clearly different, especially in the processes of single-spore development. Pathogenicity studies showed that 7 species damaged the liver and skin in mice, and their pathogenicity was stronger than other 4 species. T. asteroides had the strongest pathogenicity and might provoke invasive infection. The pathological characteristics of liver and skin infections caused by different Trichosporon spp. were similar. So it is necessary to identify the species of Trichosporon on the surface of giant panda. Combination of ITS, D1/D2, and IGS1 loci analysis, and morphological development process can effectively identify the genotype of Trichosporon spp.

microbiology↗

bioRxiv2018

Carbon starvation-induced lipoprotein Slp directs the synthesis of catalase and expression of OxyR regulator to protect against hydrogen peroxide stress in Escherichia coli

Escherichia coli can induce a group of stress-response proteins, including carbon starvation-induced lipoprotein (Slp), which is an outer membrane lipoprotein expressed in response to stressful environments. In this paper, slp null mutant\n\nE. coli were constructed by insertion of the group II intron, and then the growth sensitivity of the slp mutant strain was measured under 0.6% (vol/vol) hydrogen peroxide. The changes in resistance to hydrogen peroxide stress were investigated by detecting antioxidant activity and gene expression in the slp mutant strain. The results showed that deletion of the slp gene increased the sensitivity of E. coli under 0.6% (vol/vol) hydrogen peroxide oxidative stress. Analysis of the unique mapping rates from the transcriptome libraries revealed that four of thirteen remarkably up/down-regulated genes in E. coli were involved in antioxidant enzymes after mutation of the slp gene. Mutation of the slp gene caused a significant increase in catalase activity, which contributed to an increase in glutathione peroxidase activity. The katG gene was activated by the OxyR regulator, which was activated directly by 0.6% (vol/vol) hydrogen peroxide, and HPI encoded by katG was induced against oxidative stress. Therefore, the carbon starvation-induced lipoprotein Slp regulates the expression of antioxidant enzymes and the transcriptional activator OxyR in response to the hydrogen peroxide environment, ensuring that cells are protected from hydrogen peroxide oxidative stress at the level of enzyme activity and gene expression.

molecular biology↗

bioRxiv2018

Modified TCA/acetone precipitation of proteins for proteomic analysis

Protein extracts obtained from cells or tissues often require removal of interfering substances for the preparation of high-quality protein samples in proteomic analysis. A number of protein extraction methods have been applied to various biological samples. TCA/acetone precipitation and phenol extraction, a common method of protein extraction, is thought to minimize protein degradation and activity of proteases as well as reduce contaminants like salts and polyphenols. However, the TCA/acetone precipitation method relies on the complete pulverization and repeated rinsing of tissue powder to remove the interfering substances, which is laborious and time-consuming. In addition, by prolonged incubation in TCA/acetone, the precipitated proteins are more difficult to re-dissolve. We have described a modified method of TCA/acetone precipitation of plant proteins for proteomic analysis. Proteins of cells or tissues were extracted using SDS-containing buffer, precipitated with equal volume of 20% TCA/acetone, and washed with acetone. Compared to classical TCA/acetone precipitation and simple acetone precipitation, this protocol generates comparable yields, spot numbers, and proteome profiling, but takes less time (ca. 45 min), thus avoiding excess protein modification and degradation after extended-period incubation in TCA/acetone or acetone. The modified TCA/acetone precipitation method is simple, fast, and suitable for proteomic analysis of various plant tissues in proteomic analysis.

biochemistry↗

bioRxiv2018

Covalent Modification and Regulation of the Nuclear Receptor Nurr1 by a Dopamine Metabolite

Nurr1, a nuclear receptor essential for the development, maintenance, and survival of midbrain dopaminergic neurons, is a potential therapeutic target for Parkinsons disease, a neurological disorder characterized by the degeneration of these same neurons. Efforts to identify Nurr1 agonists have been hampered by the recognition that it lacks several classic regulatory elements of nuclear receptor function, including the canonical ligand-binding pocket. Here we report that the dopamine metabolite 5,6-dihydroxyindole (DHI) binds directly to and modulates the activity of Nurr1. Using biophysical assays and x-ray crystallography we show that DHI binds to the ligand binding domain within a non-canonical pocket, forming a covalent adduct with Cys566. In cultured cells and zebrafish, DHI stimulates Nurr1 activity, including the transcription of target genes underlying dopamine homeostasis. These findings suggest avenues for developing synthetic Nurr1 ligands to ameliorate the symptoms and progression of Parkinsons disease.

biophysics↗

bioRxiv2018

The draft genome sequence of mandrill (Mandrillus sphinx)

BackgroundMandrill (Mandrillus sphinx) is a primate species which belong to Old World monkey (Cercopithecidae) family. It is closely related to human, serving as model for some human diseases researches. However, genetic researches and genomic resources of mandrill were limited, especially comparing to other primate species.\n\nFindingsHere we sequenced 284 Gb data, providing 96-fold coverage (considering the estimate genome size of 2.9 Gb), to construct a reference genome for mandrill. The assembled draft genome was 2.79 Gb with contig N50 of 20.48 Kb and scaffold N50 of 3.56 Mb. We annotated the mandrill genome to find 43.83% repeat elements, as well as 21,906 protein coding genes. We found good quality of the draft genome and gene annotation by BUSCO analysis which revealed 98% coverage of the BUSCOs.\n\nConclusionsWe established the first draft genome sequence of mandrill, which is valuable resource for future evolutionary and human diseases studies.

genomics↗

bioRxiv2018

Identification of Novel Genes and Variations Associated to Glycolytic Potential Based on Pig Model

In livestock, glycolytic potential (GP) is a critical indicator for evaluating the meat quality. To date, two major genes protein kinase AMP-activated {gamma}3 non-catalytic subunit gene (PRKAG3) and phosphorylase kinase catalytic subunit gamma 1(PHKG1), and corresponding cause mutations influencing GP have been confirmed in pigs. Therefore, the aim of this study to identify the novel candidate genes and variations related to GP-related traits using a four-hybrid pig model [Pietrain (P)x Duroc (D)] x[(Landrace) x(Yorkshire)]. We totally constructed six RNA-seq libraries using longissimus dorsi (LD) muscles, and each library contained two higher GP (H) or two lower GP (L) individuals. A total of 525, 698 and 135 differentially expressed genes (DEGs) were identified between H11 vs L11, H9 vs L9, and H5 vs L5 groups using PossionDis method, respectively. Notably, we found 97 non-redundant DEGs were mapped to GP related QTLs from three paired comparison groups. Moreover, 69 DEGs were identified between H (H11, H9 and H5) and L (L11, L9 and L5) groups using NOIseq method. Additionally, 1,076 potential specific SNPs were figured out between H and L groups, and approximately 40 large Indels with a length [≥] 5bp were identified in each sequencing library. In conclusion, our data provide foundation for further confirming the key genes and the functional mutations affecting GP-related traits in pigs, and also pave the way for elucidating the underling molecular regulatory mechanisms of glycogen metabolism in future study. Moreover, this study might provide valuable information for study on human glycogen storage diseases.

genomics↗

bioRxiv2018

Can we obtain in vivo transmural mean hoop stress of the aortic wall without knowing patient-specific material properties and residual deformations?

It is well known that residual deformations/stresses alter the mechanical behavior of arteries, e.g. the pressure-diameter curves. In an effort to enable personalized analysis of the aortic wall stress, approaches have been developed to incorporate experimentally-derived residual deformations into in vivo loaded geometries in finite element simulations using thick-walled models. Solid elements are typically used to account for \"bending-like\" residual deformations. Yet, the difficulty in obtaining patient-specific residual deformations and material properties has become one of the biggest challenges of these thick-walled models. In thin-walled models, fortunately, static determinacy offers an appealing prospect that allows for the calculation of the thin-walled membrane stress without patient-specific material properties. The membrane stress can be computed using forward analysis by enforcing an extremely stiff material property as penalty treatment, which is referred to as the forward penalty approach. However, thin-walled membrane elements, which have zero bending stiffness, are incompatible with the residual deformations, and therefore, it is often stated as a limitation of thin-walled models. In this paper, by comparing the predicted stresses from thin-walled models and thick-walled models, we demonstrate that the transmural mean hoop stress is the same for the two models and can be readily obtained from in vivo clinical images without knowing the patient-specific material properties and residual deformations. Computation of patient-specific mean hoop stress can be greatly simplified by using membrane model and the forward penalty approach, which may be clinically valuable.

bioengineering↗

bioRxiv2018

Chicken uric acid elimination via the uric acid transporters BCRP and MRP4 in the liver, kidneys, and intestines

Breast cancer resistance protein (BCRP) and multidrug resistance protein 4 (MRP4) are involved in uric acid excretion in humans and mice. Despite evidence suggesting that chicken renal proximal tubular epithelial cells participate in uric acid secretion, the roles of BCRP and MRP4 in chickens remain unclear. This study evaluated the relationship between chicken BCRP and MRP4 expression and renal function in the liver, kidneys, and intestines. Sixty 20-day-old Isa brown laying hens were randomly divided into four groups: a control group (NC) and groups provided with sulfonamide-treated drinking water (SD), a diet supplemented with fishmeal (FM), and an intraperitoneal injection of uric acid (IU). Serum uric acid, creatinine, and blood urea nitrogen (BUN) levels were significantly higher in the SD and IU groups than in the NC group. BCRP and MRP4 levels in the SD and IU groups were significantly increased in the kidneys and ileum and decreased in the liver. In the FM group, BCRP and MRP4 were significantly increased in the kidneys and slightly increased in the ileum. These results demonstrate that chicken BCRP and MRP4 are involved in renal and intestinal uric acid excretion. When renal function is impaired, serum uric acid increased and BCRP and MRP4 in the liver, kidneys, and ileum exhibit compensatory increases; when renal function is normal, serum uric acid changes have no effect on ileum BCRP and MRP4 expression. Therefore, this study may provide the references to the uric acid regulation in human.

physiology↗

bioRxiv2018

Root Colonization and Growth Promotion of Soybean, Wheat and Chinese Cabbage by Bacillus cereus YL6

Phosphate-solubilizing bacteria (PSB) have been isolated and used in agricultural production. However, comprehensive research on PSB colonizing the rhizosphere of different plants and promoting plant growth is lacking. This study was conducted to study the growth-promoting effects and colonizing capacity of the PSB strain YL6. The YL6 strain not only increased the biomass of pot-planted soybean and wheat but also increased the yield and growth of Chinese cabbage under field conditions. The promotion of growth in these crops by strain YL6 was related to its capacities to dissolve inorganic and organic phosphorus and to produce a certain amount of indole-3-acetic (IAA) and gibberellin (GA). After YL6 was applied to soybean, wheat and Chinese cabbage, the rhizosphere soil available phosphorus (available P) content increased by 120.16%, 62.47% and 7.21%, respectively, and the plant total phosphorus increased by 198.60%, 6.20% and 78.89%, respectively, compared with those of plants without the addition of YL6. To determine whether the phosphate solubilizing bacteria colonized these plants, YL6 labeled with green fluorescent protein (YL6-GFP) was inoculated into plant rhizospheres. YL6-GFP first colonized the root surface and hairs and then penetrated into intercellular spaces and vessels. Collectively, these results demonstrate that YL6 promoted the growth of three different crops and colonized them in a similar way and therefore provide a solid foundation for probing into mechanisms by which phosphate-solubilizing bacteria affect plant growth.

microbiology↗

bioRxiv2018

First report and multilocus genotyping of Enterocytozoon bieneusi from Tibetan pigs in southwestern China

Enterocytozoon bieneusi is a common intestinal pathogen and a major cause of diarrhea and enteric diseases in a variety of animals. While the E. bieneusi genotype has become better-known, there are few reports on its prevalence in the Tibetan pig. This study investigated the prevalence, genetic diversity, and zoonotic potential of E. bieneusi in the Tibetan pig in southwestern China. Tibetan pig feces (266 samples) were collected from three sites in the southwest of China. Feces were subjected to PCR amplification of the internal transcribed spacer (ITS) region. E. bieneusi was detected in 83 (31.2%) of Tibetan pigs from the three different sites, with 25.4% in Kangding, 56% in Yaan and 26.7% in Qionglai. Age group demonstrated the prevalence of E. bieneusi range from 24.4%(aged 0 to 1 years) to 44.4%(aged 1 to 2 years). Four genotypes of E. bieneusi were identified: two known genotypes EbpC (n=58), Henan-IV (n=24) and two novel genotypes, SCT01 and SCT02 (one of each). Phylogenetic analysis showed these four genotypes clustered to group 1 with zoonotic potential. Multilocus sequence typing (MLST) analysis three microsatellites (MS1, MS3, MS7) and one minisatellite (MS4) revealed 47, 48, 23 and 47 positive specimens were successfully sequenced, and identified ten, ten, five and five genotypes at four loci, respectively. This study indicates the potential danger of E. bieneusi to Tibetan pigs in southwestern China, and offers basic data for preventing and controlling infections.

genetics↗

bioRxiv2018

Cold Shock Fail to Restrain Pre-formed Bacterial Biofilm

Environmental temperature fluctuation has great impact on the formation of bacterial biofilm, while little information is available for assessing the influence of sharp temperature shifts on the fate of pre-formed biofilm. In this study, experimental evidence is firstly explored on the response of Vibrio parahaemolyticus pre-formed biofilm under cold shock (4 {degrees}C and 10 {degrees}C). Surprisingly, biofilm biomass of V. parahaemolyticus significantly increased during the period of cold shock as revealed by crystal violet staining. Polysaccharides and proteins contents in extracellular polymeric substances were gradually enhanced after cold shocks and exhibited high consistency. RT-qPCR demonstrated the expression of flagella and virulence-related genes were up-regulated. Most of QS and T3SS genes were slightly up-regulated, and three T3SS genes (vcrD1, vcrD2{beta} and vopD1) were down-regulated. Furthermore, the biofilm structure of V parahaemolyticus have been analyzed by Confocal laser scanning microscopy (CLSM), which sharply changed under cold shocks. The correlation analysis further displayed the significant correlation (P < 0.01) among biofilm structure parameters, and weak correlation (P < 0.05) between biofilm related genes and biofilm structure parameters. In conclusion, our results novel discovered that V. parahaemolyticus biofilm related genes were actively expressed and biofilm biomass was continuously increased, biofilm structure was tremendously changed after cold shock. This study underscored the risk that biofilm cells had the ability to adapt to low temperature shift.\n\nIMPORTANCEBiofilms are widespread in natural environments, especially on the surface of food and medical biomaterials, which threaten human safety from persistent infections. Previous studies simply focused on biofilm formation of microorganisms under steady state, however, the actual environment frequently fluctuated. V. parahaemolyticus is a widely distributed foodborne pathogen, temperature play a great role in its survival. Researchers generally assume that cold environment can restrain biofilm formation and bacterial activity. This study explored the effects of V. parahaemolyticus biofilm upon a shift from 37 {degrees}C to 4 {degrees}C or 10 {degrees}C from two aspects. On the one hand, the changes of biofilm biomass and EPS contents, the expression of biofilm related genes directly described that pre-formed bacterial biofilm could not be controlled efficiently in cold environment. On the other hand, the CLSM images revealed biofilm morphological structure change, the correlation analysis showed inner relationship among biofilm structure parameters and biofilm related genes. These results suggested that cold shock fail to restrain pre-formed bacterial biofilm, therefore be a potential risk in nature environment.

microbiology↗

bioRxiv2018

The landscape and diagnostic potential of T and B cell repertoire in Immunoglobulin A Nephropathy

Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. In IgAN, immune complex deposite in glomerular mesangium, which induce inflammation and affect the kidneys normal functions. However, the exact pathogenesis of IgAN is still incompletely understood. Further, in current practice the clinical diagnosis relies on needle biopsy on renal tissue. Therefore, a non-invasive method for clinical diagnosis and prognosis surveillance of the disease is in high demand. In this paper, we investigated both the T cell receptor bata chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire of kidney infiltrating and circulating lymphocytes of IgAN patients by immune repertoire high throughput sequencing. We found that the features of TCRB and IGH in the renal tissues were remarkably different from that in blood, including a decreased repertoire diversity and increased IgA and IgG frequency, and more activated B cells. The CDR3 length of PBMC TCRB and IGH in patients is significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clone selection. We also found that the IgA1 frequency in the PBMC of IgAN is significant higher than that in other Nephropathy (NIgAN) and healthy control, which is consistent with the previous reports on the level of IgA1 producing B cells and serum IgA1. Significantly, we identified a set of IgAN disease related TCRB and IGH CDR3s, which can be used to distinguish IgAN from NIgAN and healthy controls from the blood with high accuracy. These results indicated that TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for IgAN diagnosis. The characteristics of kidney infiltrating and circulating lymphocytes repertoire shed light on IgAN detection, treatment and surveillance.

immunology↗