Regulatory T cells effectively downregulate the autoimmune anti-MPO response and ameliorate anti-MPO induced glomerulonephritis in mice.

Regulation of autoreactive cells is key for both prevention and amelioration of autoimmune disease. A better understanding of the key cell population(s) responsible for downregulation of autoreactive cells would provide necessary foundational insight for cellular-based therapies in autoimmune disease. Utilizing a mouse model of anti-myeloperoxidase (MPO) glomerulonephritis, we sought to understand which immune cells contribute to downregulation of the anti-MPO autoimmune response. MPO-/- mice were immunized with whole MPO to induce an anti-MPO response. Anti-MPO splenocytes were then transferred into recipient mice (Rag2-/- mice or WT mice). Anti-MPO titers were followed over time. After anti-MPO splenocyte transfer, WT mice are able to downregulate the anti-MPO response while anti-MPO titers persist in Rag2-/- recipients. Reconstitution with WT splenocytes into Rag2-/- recipients prior to anti-MPO splenocyte transfer enabled mice to downregulate the anti-MPO immune response. Therefore, wildtype splenocytes contain a cellular population that is capable of downregulating the autoimmune response. Through splenocyte transfer, antibody depletion experiments, and purified cell population transfers, we confirmed that the regulatory T cell (Treg) population is responsible for the downregulation of the anti-MPO autoimmune response. Further investigation revealed that functional Tregs from WT mice are capable of downregulating anti-MPO antibody production and ameliorate anti-MPO induced glomerulonephritis. These data underscore the importance of functional Tregs for control of autoimmune responses and prevention of end-organ damage due to autoimmunity.

Association of Obesity With Kidney and Cardiac Outcomes Among Patients With Glomerular Disease: Findings From the Cure Glomerulonephropathy Network.

RATIONALE & OBJECTIVE: The influence of obesity on cardiorenal outcomes in individuals with glomerular disease is incompletely known. This study examined the association between obesity and kidney and cardiovascular outcomes in children and adults with glomerular kidney disease. STUDY DESIGN: Prospective, multicenter, observational study. SETTING & PARTICIPANTS: Participants in the Cure Glomerulonephropathy Network (CureGN) who were≥5 years of age at enrollment. EXPOSURE: Adult body mass index (BMI) groups: 20-24 (healthy) versus 25-34 (overweight/class 1 obesity) versus≥35 (class 2-3 obesity); and pediatric BMI percentiles: 5th-84th (healthy) versus 85th-94th (overweight) versus≥95th (obese). OUTCOME: A composite kidney outcome (40% estimated glomerular filtration rate [eGFR] decline or kidney failure) and a composite cardiovascular outcome (myocardial infarction, stroke, heart failure, or death). ANALYTICAL APPROACH: Time to composite primary outcomes by BMI strata were estimated using Kaplan-Meier analysis. The adjusted associations between BMI and outcomes were estimated using Cox proportional hazards analysis. RESULTS: The study included 2,301 participants (1,548 adults and 753 children). The incidence of the primary kidney end point was 90.8 per 1,000 person-years in adults with class 2-3 obesity, compared with 58.0 in normal weight comparators. In the univariable analysis, class 2-3 obesity was associated with the primary kidney outcome only in adults (HR, 1.6 [95% CI, 1.1-2.2], P=0.006) compared with the healthy weight groups. In the multivariable adjusted analysis, class 2-3 obesity did not remain significant among adults when controlling for baseline eGFR and proteinuria. Adults with class 2-3 obesity had an incidence of 19.7 cardiovascular events per 1,000 person-years and greater cardiovascular risk (HR, 3.9 [95% CI, 1.4-10.7], P=0.009) in the fully adjusted model. LIMITATIONS: BMI is an imperfect indicator of adiposity. Residual confounding may exist from socioeconomic factors. CONCLUSIONS: Among adult patients in CureGN, class 2-3 obesity is associated with cardiovascular but not kidney outcomes when adjusted for potential confounding factors. PLAIN-LANGUAGE SUMMARY: Obesity is a risk factor for adverse heart and kidney outcomes in patients with chronic kidney disease, but whether it is associated with these outcomes in patients with glomerulonephropathy is not known. This study used existing data from a large sample of adults and children with glomerular diseases to address this question. The findings suggest that obesity increases the risk of cardiovascular but not kidney disease events in adult patients with glomerular disease.

Infections Following Kidney Transplantation After Exposure to Immunosuppression for Treatment of Glomerulonephritis.

RATIONALE & OBJECTIVE: Kidney transplant patients with glomerulonephritis (GN) as their native disease commonly have received pretransplant immunosuppression (PTI). This may contribute to the immunosuppression burden potentially increasing the risk for infections after transplantation. STUDY DESIGN: Single-center, retrospective cohort study. SETTING & PARTICIPANTS: Recipients of a kidney transplant from January 2005 until May 2020 at a tertiary care university teaching hospital. EXPOSURE: Patients with GN as their native kidney disease who received PTI for treatment of GN (n=184) were compared with nondiabetic recipients of kidney transplants who did not receive PTI (n = 579). OUTCOME: First occurrence after transplantation of an infection outcome, either viral (BK or cytomegalovirus [CMV] infection) or bacterial. ANALYTICAL APPROACH: Cox regression analysis adjusted for age at transplant, sex, race, donor type, year of transplant surgery, dialysis vintage, receipt of T-cell depleting induction, and CMV transplant status. RESULTS: Over a median follow-up period of 5.7 years, patients with GN PTI were not at an increased risk for developing any first viral infection compared with controls (adjusted HR [AHR] 0.69 [95% CI, 0.52-0.91]) nor at increased risk for specific viral infections: BK infection 19.6% vs 26.3% (AHR 0.72 [95% CI, 0.50-1.05]) or CMV infection, 24.5% vs 29.0% (AHR, 0.76 [95% CI, 0.54-1.07]), respectively. There was also no increased risk of developing a first bacterial infection: 54.5% vs 57.5% (AHR, 0.90 [95% CI, 0.71-1.13]). These findings of no increased risk for infection were independent of the type of PTI used (cyclophosphamide, rituximab, mycophenolate mofetil, or calcineurin inhibitor) or the type of T-cell depleting induction therapy (alemtuzumab or antithymocyte globulin) administered. LIMITATIONS: Single-center study, no data on methylprednisone use for PTI, unmeasured confounding. CONCLUSIONS: Use of PTI for the treatment of GN was not associated with an increased risk of viral (BK or CMV) or bacterial infection after transplantation. Additional surveillance for infection after transplantation for patients who received PTI may not be necessary. PLAIN-LANGUAGE SUMMARY: Many kidney transplant patients have glomerular disease as the cause of kidney failure. These patients may be exposed to immunosuppression before transplantation, which could increase the risk for infections after receipt of a transplanted kidney. We identified kidney transplant recipients at a university teaching hospital who received immunosuppression before transplant for the treatment of glomerular kidney disease. We examined their risk for infection after transplantation by comparing it with the risk among transplant patients who were not exposed to immunosuppression before transplant. We observed no increased risk for infection after exposure to prior immunosuppression. Therefore, patients exposed to significant amounts of immunosuppression before transplantation may not require special surveillance or medication adjustment for fear of infection after their receipt of a kidney transplant.

Malignancy risk in kidney transplant recipients exposed to immunosuppression pre-transplant for the treatment of glomerulonephritis.

BACKGROUND: Kidney transplant patients with glomerulonephritis (GN) as their native disease may receive significant amounts of pre-transplant immunosuppression (PTI), which could increase the risk for development of malignancy post-transplant. METHODS: We conducted a single-center, retrospective study of kidney transplant recipients from January 2005 until May 2020. Patients with GN as their native kidney disease who received PTI for treatment of GN (n = 184) were compared with a control cohort (n = 579) of non-diabetic, non-PTI-receiving kidney transplant patients. We calculated hazard ratios (HR) with 95% confidence intervals (95% CI) for outcomes of first occurrence of solid or hematologic malignancy, non-melanoma skin cancer (NMSC) and post-transplant lymphoproliferative disorder (PTLD). RESULTS: Over a median follow-up of 5.7 years, PTI for GN was associated with significantly increased risk for malignancy compared with controls [13.0%  vs 9.7%, respectively; adjusted HR 1.82 (95% CI 1.10-3.00)], but not for NMSC [10.3% vs 11.4%, respectively; adjusted HR 1.09 (95% CI 0.64-1.83)] or PTLD [3.3% vs 3.1%, respectively; adjusted HR 1.02 (95% CI 0.40-2.61)]. The risk for malignancy was significantly increased in those who received cyclophosphamide [HR 2.59 (95% CI 1.48-4.55)] or rituximab [HR 3.82 (95% CI 1.69-8.65)] pre-transplant, and particularly in those who received both cyclophosphamide and rituximab, but not for calcineurin inhibitors or mycophenolate. CONCLUSION: The use of PTI for treatment of GN, especially cyclophosphamide or even with rituximab, is associated with increased risk for development of solid or hematologic malignancy post-transplant. These data highlight potential risks with treatment of GN and underscore the importance of post-transplant malignancy surveillance in this patient population.

Immunological Interaction of HLA-DPB1 and Proteinase 3 in ANCA Vasculitis is Associated with Clinical Disease Activity.

BACKGROUND: PR3-ANCA vasculitis has a genetic association with HLA-DPB1. We explored immunologic and clinical features related to the interaction of HLA-DPB1*04:01 with a strongly binding PR3 peptide epitope (PR3225-239). METHODS: Patients with ANCA vasculitis with active disease and disease in remission were followed longitudinally. Peripheral blood mononuclear cells from patients and healthy controls with HLA-DPB1*04:01 were tested for HLA-DPB1*04:01 expression and interaction with a PR3 peptide identified via in silico and in vitro assays. Tetramers (HLA/peptide multimers) identified autoreactive T cells in vitro. RESULTS: The HLA-DPB1*04:01 genotype was associated with risk of relapse in PR3-ANCA (HR for relapse 2.06; 95% CI, 1.01 to 4.20) but not in myeloperoxidase (MPO)-ANCA or the combined cohort. In silico predictions of HLA and PR3 peptide interactions demonstrated strong affinity between ATRLFPDFFTRVALY (PR3225-239) and HLA-DPB1*04:01 that was confirmed by in vitro competitive binding studies. The interaction was tested in ex vivo flow cytometry studies of labeled peptide and HLA-DPB1*04:01-expressing cells. We demonstrated PR3225-239 specific autoreactive T cells using synthetic HLA multimers (tetramers). Patients in long-term remission off therapy had autoantigenic peptide and HLA interaction comparable to that of healthy volunteers. CONCLUSIONS: The risk allele HLA-DPB1*04:01 has been associated with PR3-ANCA, but its immunopathologic role was unclear. These studies demonstrate that HLA-DPB1*04:01 and PR3225-239 initiate an immune response. Autoreactive T cells specifically recognized PR3225-239 presented by HLA-DPB1*04:01. Although larger studies should validate these findings, the pathobiology may explain the observed increased risk of relapse in our cohort. Moreover, lack of HLA and autoantigen interaction observed during long-term remission signals immunologic nonresponsiveness.

[Relationship between vitamin D and parathyroid hormone in Chinese elderly people].

OBJECTIVE: To explore the relationship between serum 25-hydroxyvitamin D(25(OH)D) and serum parathyroid hormone(PTH) level in Chinese people aged 50 years and above, and to probe the optimum threshold for vitamin D sufficiency preliminarily, and apply this threshold to predict the risk of metabolic syndrome(Mets) in this population. METHODS: A total of 750 serum samples were selected from the biological samples' bank of Chinese Chronic Diseases and Nutritional Survey(CCDNS, 2015-2017) by stratified sampling, basic information(including age, gender, season, etc. ) were collected from questionnaire and physical measurement of the subjects were conducted unified. Serum 25(OH)D concentration was determined by high performance liquid chromatography tandem mass spectrometer, and PTH and interleukin-6(IL-6) were detected by electrochemiluminescence method. Phosphorus, albumin(Alb), creatinine(Cr) in blood were detected by automatic biochemical analyzer. Factors affecting the concentration of 25(OH)D and PTH were found by multiple linear regression and adjusted by generalized additive model separately, threshold was predicted by locally weighted regression and smoothing scatterplot, abbreviated as LOESS, and the exact threshold of 25(OH)D was found when PTH reached the plateau by nonlinear least squares estimation and segmented regression. Relationship between 25(OH)D and Mets was analyzed by multivariate logistic regression using the different cut-off points in Chinese elderly people. RESULTS: Reference threshold for vitamin D deficiency in Chinese elderly people can be preliminarily discovered as serum total 25(OH)D was 19.62 ng/mL, and 28.44 ng/mL can be used as reference threshold for sufficient vitamin D. Sufficient 25(OH)D(≥28.44 ng/mL) could reduce the risk of Mets significantly(OR=0.617(0.439-0.869)) after adjusting for confounding factors such as sex, age, region, season, ect. A plateau in PTH was observed at a 25(OH)D concentration of 20.03-28.43 ng/mL for male whereas 13.12-26.33 ng/mL for female by gender stratification analysis, but no cut-off point was obtained statistically. CONCLUSION: Reference threshold for vitamin D sufficiency in Chinese elderly people was preliminarily observed in the range of 19.62-28.44 ng/mL when PTH was maximally inhibited, and the threshold may vary with gender. Applying the threshold we also found that more sufficient levels of vitamin D were protective against Mets in this population.

[Protein efficiency ratio of genetically modified pork powder with fat-1 gene].

OBJECTIVE: To evaluate the protein efficiency ratio(PER) of genetically modified pork powder with fat-1 gene(GM group), and thus evaluate whether the nutritional evaluation value of fat-1 gene pork powder has changed. METHODS: Sixty weaned SD rats(60-80 g) were randomly divided into casein group, parental control group and GM group according to sex and weight, 20 rats in each group, half of each sex. The rats in the three groups were fed with corresponding formulated feed containing 10% protein for 28 days. The body weight and food intake of each group were recorded weekly. Blood was collected at the end of the experiment to determine hematology and blood biochemical indexes. The food utilization rate, organ/body weigh indexes, PER and corrected PER were calculated. RESULTS: The weight of rats in all groups increased steadily during the experimental period. Statistically significant differences were found in some hematology and blood biochemical indexes and organ/body weigh indexes. No biologically significant changes were found. The food utilization rate of GM group was higher than that of casein group(P<0.05), which was equivalent to that in the parental control group. The PER of both genetically modified pork powder with fat-1 gene and parental white pork powder were higher than that of casein(P<0.05). CONCLUSION: The PER of genetically modified pork powder with fat-1 gene was equal to that of its parental white pork powder.

[Plasma selenium level and its influencing factors in Chinese child-bearing-aged women in 2015].

OBJECTIVE: To assess the plasma selenium(Se) level of child-bearing-aged women and discuss the influence factor for low-Se level. METHODS: Using the muti-stage stratified and population proportional cluster random sampling method, 1881 child-bearing-aged women aged 18 to 44 years were selected from China Adult Chronic Disease and Nutrition Surveillance(2015) Data. The basic information of the subjects was collected by unified electronic questionnaires and equipments were used for field survey, measurement and record. Plasma Se concentration was detected by inductively coupled plasma mass spectrometry. Plasma low-Se level were assessed using lower limit of plasma/serum Se established by the Mayo Clinic Laboratory and our laboratory, respectively. Influence factors of low-Se level were analyzed by the multivariate logistic regression model. RESULTS: The M(P25, P75) plasma Se concentration for Chinese child-bearing-aged women was 89.52(74.21, 105.03)µg/L. Nationality, location, urban-rural type and education level difference had influence on plasma Se level in this population(P<0.05). According to the lower limit of plasma/serum Se concentration established by the Mayo clinical laboratories(<70 µg/L) and our laboratories(<73.81 µg/L), the low-Se rate were 20.47% and 24.51%, respectively. There were significantly differences in low-Se rate among nationality, location, urban-rural type, education level and marital status(P<0.05). The multivariate logistic regression model showed that location and urban-rural type had significant effects on low-Se rate of child-bearing-aged women(P<0.05). CONCLUSION: The plasma low-Se rate of Chinese women of childbearing age is relatively high and higher prevalence low-Se was found in western and central regions and rural areas in China.

Kidney thrombotic microangiopathy in lupus nephritis: Impact on treatment and prognosis.

INTRODUCTION: Lupus nephritis (LN) may present with thrombotic microangiopathy (TMA) on kidney biopsy, the impact of which on outcomes is unclear. This study examined the prognostic importance of LN with TMA on kidney biopsy, including response to therapy and long-term outcomes. METHODS: We conducted a single-center, retrospective study of all cases of LN with concomitant TMA on kidney biopsy in the Glomerular Disease Collaborative Network database. Controls were individuals with LN without TMA matched to cases based on demographic and clinical variables. Outcomes were remission at 6- and 12-months, end-stage kidney disease (ESKD) and death. Logistic regression and Cox proportional hazards models were used to ascertain the risks for outcomes, with adjustment for serum creatinine and proteinuria. RESULTS: There were 17 cases and 28 controls. Cases had higher creatinine, higher proteinuria and greater chronicity on biopsy at baseline compared to controls. The rates of remission at 6-months and 12-months were similar between cases and controls (6-months 53.9% vs 46.4%, adjusted OR 2.54, 95% CI 0.48, 13.37; 12-months 53.9% vs 50.0%, adjusted OR 2.95, 95% CI 0.44, 19.78). Cases were at greater risk for ESKD in univariate analysis (HR 3.77; 95% CI 1.24, 11.41) but not when adjusting for serum creatinine and proteinuria (HR 2.20; 95% CI 0.63, 7.71). There was no significant difference in the risk of death between cases and controls. CONCLUSION: Lupus nephritis with renal TMA likely responds to therapy similarly to those without TMA; risk for ESKD is not significantly increased, although the influence of renal function and proteinuria in larger samples is needed.

[Association of vitamin D gene polymorphisms and serum 25-hydroxyvitamin D in Chinese women of childbearing age].

OBJECTIVE: To analyze the relationship between vitamin D(VitD)-related single nucleotide polymorphism(SNP) and 25-hydroxyvitamin D(25(OH) D) levels and VitD nutritional status. METHODS: A total of 1507 women of childbearing age aged 18-45 were selected from the sample bank of "2015 Chinese adult chronic disease and nutrition monitoring". Basic information(including region, season, age, height, weight, etc. ) of the subjects was collected. The SNPs related to VitD metabolism were screened, and the improved multiple ligase detection reaction was used for SNP testing. Liquid chromatography tandem mass spectrometry was used to determine the serum 25(OH)D concentration. The effects of genotypes on 25(OH)D level and VitD deficiency were analyzed by generalized linear model and binary logistic regression model, respectively. RESULTS: After adjusting for latitude, region, region type, season and age, CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 were associated with serum 25(OH)D levels in women of childbearing age. The risk of VitD deficiency in individuals carrying GG genotype at rs2282679 was significantly higher than that in individuals carrying TT genotype(OR=2.466, 95%CI 1.690-3.598, P<0.001), and the risk of VitD deficiency in individuals carrying A allele at rs2228570 was lower than that in individuals carrying G allele(OR_(AA)=0.625, 95%CI 0.446-0.876, P_(AA)=0.006;OR_(GA)=0.661, 95%CI 0.502-0.869, P_(GA)=0.003). CONCLUSION: The genotype distribution of CYP2R1 rs12794714, GC rs2282679, GC rs7041 and VDR rs2228570 may be related to serum 25(OH)D level or VitD nutritional status of Chinese women of childbearing age.

[Vitamin A nutrition status of Chinese urban adults aged 18 to 60 years old in 2015].

OBJECTIVE: To investigate the vitamin A nutritional status and its related influencing factors of Chinese 18-60 urban adults by analyzing serum retinol level in 2015. METHODS: Serum samples of 42 people, half male and half female, were randomly selected in each point, from the 302 monitoring sites of Chinese adult chronic diseases and nutrition surveillance in 2015. The serum retinol levels were determined by high pressure liquid chromatography(HPLC). RESULTS: A total of 2571 serum samples were detected. The serum retinol level of Chinese urban adults of 18-60 years old was 1.98(1.56-2.53)µmol/L, the deficiency rate was 0.25%, and the marginal deficiency rate was 4.45%. The serum retinol level of male was 2.19(1.75-2.78)µmol/L, the deficiency rate was 0.05%, and the marginal deficiency rate was 2.48%; The serum retinol level of female was 1.80(1.42-2.25)µmol/L, the deficiency rate was 0.46%, and the marginal deficiency rate was 6.51%. The significant differences in serum retinol was observed deficiency rate and marginal deficiency rate between males and females(P<0.01), the nutritional status of males was better than the females. The deficiency rate and marginal deficiency rate of 18-29 years old were the highest, which were 0.34% and 5.81% respectively. The deficiency rate and marginal deficiency rate of over 50 years old were the lowest, which were 0.15% and 2.60% respectively. The vitamin A deficiency rate and marginal deficiency rate of people with body mass index(BMI)<18.5 were 0.95% and 7.24%, 0.33% and 5.85% for BMI=18.5-23.9, 0.13% and 3.27% for BMI=24.0-27.9, respectively. The differences of vitamin A deficiency rate and marginal deficiency rate among different BMI were significant. CONCLUSION: The vitamin A nutritional status of urban adults in China is good, the vitamin A deficiency rate is very low, and the incidence of vitamin A deficiency is also low. It is basically not a public health problem according the WHO standard.

[Protein efficiency ratio of genetically modified corn with Cry1Ab-ma gene].

OBJECTIVE: To evaluate the protein efficiency ratio(PER) of genetically modified corn with Cry1Ab-Ma gene and parental corn. METHODS: Sixty SD rats(60-80 g) were randomly divided into genetically modified corn group, parental corn group and casein control group, with 20 rats in each group and half male and half female. Casein was added to 10% of the diet in casein control group. When the protein content of the diets in the genetically modified corn group and parental corn group was still less than 10% according to the principle of maximum incorporation, the defective part was supplemented with casein. Rats were free to drink and eat for 28 days. Food intake and body weight of each group were recorded every week. Blood was collected at the end of the experiment to determine hematology and blood biochemical indexes. The main organs were weighed and organ/body weigh indexes were calculated. PER and corrected PER were calculated. RESULTS: The body weight of all the animals in each group showed an increasing trend, and the weight growth was normal. Although there were statistical differences in the individual indexes of end-stage hematology and blood biochemical indexes, there was no biological significance. There were no significant change in the organ/body weigh indexes. PER of genetically modified corn, parental corn and casein were 2.01±0.22, 1.77±0.30 and 3.64±0.48, respectively. The corrected PER of genetically modified corn and parent corn were 1.38 and 1.22, respectively. CONCLUSION: The PER of this batch of genetically modified corn with Cry1Ab-ma gene was better than that of parental corn, but worse than that of casein.

Podocyte density is reduced in kidney allografts with high-risk APOL1 genotypes at transplantation.

Variants in apolipoprotein L1 (APOL1) gene are associated with nondiabetic kidney diseases in black subjects and reduced kidney transplant graft survival. Living and deceased black kidney donors (n = 107) were genotyped for APOL1 variants. To determine whether allografts from high-risk APOL1 donors have reduced podocyte densities contributing to allograft failure, we morphometrically estimated podocyte number, glomerular volume, and podocyte density. We compared allograft loss and eGFR trajectories stratified by APOL1 high-risk and low-risk genotypes. Demographic characteristics were similar in high-risk (n = 16) and low-risk (n = 91) donors. Podocyte density was significantly lower in high-risk than low-risk donors (108 ± 26 vs 127 ± 40 podocytes/106 um3 , P = .03). Kaplan-Meier graft survival (high-risk 61% vs. low-risk 91%, p-value = 0.049) and multivariable Cox models (hazard ratio = 2.6; 95% CI, 0.9-7.8) revealed higher graft loss in recipients of APOL1 high-risk allografts over 48 months. More rapid eGFR decline was seen in recipients of high-risk APOL1 allografts (P < .001). At 60 months, eGFR was 27 vs. 51 mL/min/1.73 min2 in recipients of APOL1 high-risk vs low-risk kidney allografts, respectively. Kidneys from high-risk APOL1 donors had worse outcomes versus low-risk APOL1 genotypes. Lower podocyte density in kidneys from high-risk APOL1 donors may increase susceptibility to CKD from subsequent stresses in both the recipients and donors.

[Vitamin A nutrition status among pregnant women in rural China in 2015].

OBJECTIVE: To evaluate the nutrition status of vitamin A in Chinese rural pregnant women from the Chinese National Nutrition and Health Survey 2015(CNNHS 2015). METHODS: A total of 3273 Chinese rural pregnant women were recruited in this study. The concentrations of serum retinol were determined using high performance liquid chromatography. The C-reactive protein and α-acid glycoprotein were determined by immunoturbidimetric method. The distribution of serum retinol status in pregnant women was further described for different regions, age groups, nationalities, body mass index(BMI), education levels, gestational weeks, family income per capita and inflammation levels. The prevalence of vitamin A deficiency and the percentage of marginal vitamin A deficiency in pregnant women were compared in different subgroups. RESULTS: The median concentration of serum retinol(M(P25, P75)) was 0. 47(0. 36, 0. 61) mg/L. There were significant differences among different regions, age groups, education levels, gestational age and per capita household income(P<0. 01). The prevalence of vitamin A deficiency was 1. 2% for deficiency and 10. 5% for marginal deficiency, respectively. Significant differences were observed in age groups, gestational weeks and inflammation levels(P<0. 01). In addition, the prevalence of vitamin A deficiency was relatively serious, 2. 1% for deficiency and 14. 2% for marginal deficiency in the third trimester, 2. 0% for deficiency and 12. 2% for marginal in the 30-44 years. CONCLUSION: It should be pay more attention on the vitamin A nutrition status in the third trimester and the 30-44 years old pregnant women, although the vitamin A status had been greatly improved in Chinese rural pregnant women.

[Vitamin A nutrition status and influencing factors of Chinese rural elderly in 2015].

OBJECTIVE: To analyze the level of vitamin A and its influencing factors of Chinese rural elderly. METHODS: The serum samples of the rural elderly were selected by random sampling method from the biological sample bank of Chinese Adults Nutrition and Chronic Diseases Surveillance in 2015(CANCDS2015). The basic information of the subjects was collected by questionnaire survey. High performance liquid chromatography(HPLC) method was used to determine the vitamin A nutritional status of the population according to the standard recommended by WHO. Multiple logistic regression analysis was explored the relationship between vitamin A status with the potential relevant factors. RESULTS: A total of 3134 elderly from Chinese rural were included in this study. The serum vitamin A concentration(M(P25, P75))was 1. 92(1. 50, 2. 45)µmoL/L. The prevalence of vitamin A deficiency was 0. 99%(95%CI 0. 64%-1. 34%), and the prevalence of vitamin A marginal deficiency was 4. 38%(95%CI 3. 65%-5. 10%). The prevalence of vitamin A marginal deficiency was significantly higher in elderly lived in western region than that lived in eastern and central regions of China. The serum vitamin A adequacy rate of rural elderly who were 80 years old and above or thin was relatively low(P<0. 05). Married elderly had significant lower vitamin A deficiency rate. The result from multivariate logistic regression model analysis showed that gender, age and body mass index had significant effects on vitamin A nutritional status of Chinese urban elderly(P<0. 05). CONCLUSION: The nutritional status of vitamin A in rural elderly in China was better, and the deficiency rate was lower.

[Relationship between rs7041 polymorphism of GC gene and serum vitamin D status in Chinese women of childbearing age].

OBJECTIVE: To investigate the association of rs7041 polymorphism of GC gene that encodes the vitamin D-binding protein with serum vitamin D status in Chinese women of childbearing age. METHODS: A total of 1812 plasma samples of women childbearing aged 18-44 years old were selected by stratified random sampling technology from the established biological samples bank of Chinese Chronic Diseases and Nutrition Survey(CCDNS, 2015-2018). The serum 25(OH)D status was detected by enzyme-linked immunosorbent assay. The genotypes of rs7041 in the GC gene were analyzed by improved multiple ligase detection reaction method. RESULTS: A total of 1812 childbearing women aged 18-49 years were included in this study. The frequency of rs7041 genotypes in the study were distributed according to the Hardy-Weinberg equilibrium, indicating sufficient representativeness of our sample. The median serum 25(OH)D status was 16. 69(12. 04, 21. 69)ng/mL. The higher 25(OH)D levels was detected in the overall sample, southern women or women with normal vitamin D status with the CC genotype than the AA genotype(P<0. 05). Before and after correction, the risk of vitamin D insufficiency in the women carrying the CC genotype was decreased significantly compared with the women carrying the AA genotype(OR=0. 571, 95%CI 0. 373-0. 873). And the CC genotype of rs7041 was associated with a significant decrease in risk of 25(OH)D deficiency(in the subgroup of southern childbearing women, OR=0. 284, 95%CI 0. 144-0. 560 and in the subgroup of northern childbearing women, OR=0. 109, 95%CI 0. 015-0. 798). CONCLUSION: The GC rs7041 with A/C polymorphism are significantly correlated with 25(OH)D status in Chinese childbearing women, mutant CC genotype is a protective factor for vitamin D non-normal status risks.

[Zinc status of 18-60 year-old adults in China in 2015].

OBJECTIVE: To estimate the distribution of serum zinc levels, zinc deficiency status and possible influencing factors in 18-60 year-old adults in China. METHODS: Based on the data of China Adult Chronic Disease and Nutrition Surveillance, 3903 blood samples were selected by stratified random sampling. The distribution of serum zinc in adults with different gender, age, regional type and regional distribution were analyzed by inductively coupled plasma mass spectrometry and body mass index(BMI), exercise, smoking, drinking, vitamin A level and other factors on serum zinc concentration and zinc deficiency rate. Multivariate logistic regression model was used to analyze the correlation between zinc deficiency and the influencing factors. RESULTS: In 2015, the median of serum zinc in Chinese adults aged 18-60 years was 103. 44(95%CI 64. 84-186. 12) µg/dL, and the overall zinc deficiency rate was 6. 04%. Serum zinc concentration had statistically significant difference(P<0. 05) in different genders, regional types, regional distribution, vitamin A status, smoking status, drinking status. In the comparison of zinc deficiency rates, ethnic minorities(10. 67 %) was higher than Han(5. 44%), rural area(7. 35%) was higher than urban area(4. 90%), vitamin A deficiency group(9. 12%) was higher than vitamin A normal group(5. 90%), non-exercise group(6. 29%) was higher than sports group(5. 09%). Among different regional distributions, the western region had the highest zinc deficiency rate(7. 33%), and among different BMI groups overweight group had the lowest rate(4. 81%). These differences were statistically significant(P<0. 05). In the analysis of multivariate logistic regression, the risk of zinc deficiency in the vitamin A deficiency group was 1. 89 higher than that of the normal group(OR=1. 89, 95%CI 1. 13-3. 18); and the overweight group had a lower risk of serum zinc deficiency than the normal group(OR=0. 71, 95%CI 0. 52-0. 96). CONCLUSION: The prevalence of serum zinc deficiency among adults aged 18-60 in China is relatively low. Vitamin A deficiency is a risk factor for zinc deficiency and overweight is a protective factor for zinc deficiency.

ANCA autoantigen gene expression highlights neutrophil heterogeneity where expression in normal-density neutrophils correlates with ANCA-induced activation.

ANCA vasculitis is an autoimmune disease with increased expression of the autoantigen genes, myeloperoxidase (MPO) and proteinase 3 (PRTN3), but the origin and significance of expression is less distinct. To clarify this, we measured MPO and PRTN3 messenger RNA in monocytes, normal-density neutrophils, and in enriched leukocytes from peripheral blood mononuclear cells. Increased autoantigen gene expression was detected in normal-density neutrophils and enriched leukocytes from patients during active disease compared to healthy individuals, with the largest difference in enriched leukocytes. RNA-seq of enriched leukocytes comparing active-remission pairs identified a gene signature for low-density neutrophils. Cell sorting revealed low-density neutrophils contained mature and immature neutrophils depending on the presence or absence of CD10. Both populations contributed to autoantigen expression but the frequency of immature cells in low-density neutrophils did not correlate with low-density neutrophil MPO or PRTN3 expression. Low-density neutrophils were refractory to MPO-ANCA induced oxidative burst, suggesting an alternative role for low-density neutrophils in ANCA vasculitis pathogenesis. In contrast, normal-density neutrophils were activated by MPO-ANCA and monoclonal anti-PR3 antibody. Normal-density neutrophil activation correlated with MPO and PRTN3 mRNA. Increased autoantigen gene expression originating from the mature low-density and normal-density neutrophils suggests transcriptional dysregulation is a hallmark of ANCA vasculitis. Thus, the correlation between autoantigen gene expression and antibody-mediated normal-density neutrophil activation connects autoantigen gene expression with disease pathogenesis.

Restricted myeloperoxidase epitopes drive the adaptive immune response in MPO-ANCA vasculitis.

BACKGROUND: Treatment of autoimmune diseases has relied on broad immunosuppression. Knowledge of specific interactions between human leukocyte antigen (HLA), the autoantigen, and effector immune cells, provides the foundation for antigen-specific therapies. These studies investigated the role of HLA, specific myeloperoxidase (MPO) epitopes, CD4+ T cells, and ANCA specificity in shaping the immune response in patients with anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis. METHODS: HLA sequence-based typing identified enriched alleles in our patient population (HLA-DPB1*04:01 and HLA-DRB4*01:01), while in silico and in vitro binding studies confirmed binding between HLA and specific MPO epitopes. Class II tetramers with MPO peptides were utilized to detect autoreactive CD4+ T cells. TCR sequencing was performed to determine the clonality of T cell populations. Longitudinal peptide ELISAs assessed the temporal nature of anti-MPO447-461 antibodies. Solvent accessibility combined with chemical modification determined the buried regions of MPO. RESULTS: We identified a restricted region of MPO that was recognized by both CD4+ T cells and ANCA. The autoreactive T cell population contained CD4+CD25intermediateCD45RO+ memory T cells and secreted IL-17A. T cell receptor (TCR) sequencing demonstrated that autoreactive CD4+ T cells had significantly less TCR diversity when compared to naïve and memory T cells, indicating clonal expansion. The anti-MPO447-461 autoantibody response was detectable at onset of disease in some patients and correlated with disease activity in others. This region of MPO that is targeted by both T cells and antibodies is not accessible to solvent or chemical modification, indicating these epitopes are buried. CONCLUSIONS: These observations reveal interactions between restricted MPO epitopes and the adaptive immune system within ANCA vasculitis that may inform new antigen-specific therapies in autoimmune disease while providing insight into immunopathogenesis.

[Exploring study on the cutoff of vitamin D deficiency in Chinese adults].

OBJECTIVE: To study the relationship between 25-hydroxyvitamin D [25(OH)D] concentration and intact parathyroid hormone(iPTH) concentration in the Chinese non-clinical population aged 18-44 y, and to explore the threshold value of determining the appropriate nutritional status of vitamin D. METHODS: A total of 650 plasma samples of adults aged 18-44 years old were selected from the established biological samples' bank of Chinese Chronic Diseases and Nutrition Survey(CCDNS, 2015-2018). Basic information(including age, gender, region type, season, etc. ) was collected by questionnaires, and the waist circumference, height and weight of the subjects were determined unified. North and South area was divided by Qinling Mountains and Huaihe River. The serum 25(OH)D concentration was determined by high performance liquid chromatography tandem mass spectrometer, and the iPTH was determined by electronic chemiluminescence method. The relationship of 25(OH)D and iPTH were analyzed by partial correlation analysis, and the threshold of 25(OH)D was analyzed by locally weighted scatter plot smoothing method after adjusting the iPTH by age, season of blood draw, BMI, waist, sex and latitude. RESULTS: A total of 623 serum samples(293 male, 330 female) of 25(OH)D concentration and iPTH concentration were analyzed after excluding samples with poor blood sample quality. Significant higher 25(OH)D concentration was found in male than female(P<0. 0001). And the samples from the southern China had higher 25(OH)D concentration than those from the northern China(P<0. 0001). Samples from autumn had higher 25(OH)D concentration than those from spring and winter(P<0. 0001). The 25(OH)D concentration of samples from cities was lower than that of rural areas(P=0. 018). The inversely relationship between 25(OH)D concentration and iPTH concentration was observed when the 25(OH)D was below 17. 6 ng/mL for both sexes. The threshold of 25(OH)D for male was 16. 2 ng/mL and it was 25. 6 ng/mL for female. CONCLUSION: The threshold and the relationship between 25(OH)D and iPTH differs by sex among Chinese adults aged 18-44 y. Further study is needed to evaluate the sex-specific ranges of optimal vitamin D.