[Application value of anti-carbamylated protein antibody in the diagnosis of rheumatoid arthritis].

OBJECTIVE: To investigate the expression level and application value of anti-carbamylated protein (CarP) antibody in rheumatoid arthritis (RA). METHODS: Demographic data and laboratory test results of RA patients, non-RA patients and healthy controls in the physical examination center were reviewed from December 2018 to June 2019 in the Rheumatology and Immunology Department of the People' s Hospital of Xinjiang Uygur Autonomous Region. The serum concentrations of anti-CarP antibodies in all the subjects were measured by ELISA and statistically analyzed. RESULTS: A total of 259 subjects were included in this study, including 158 in the RA group (45 serum-negative RA patients), 59 in the non-RA group and 42 in the healthy control group. The concentration of anti-CarP antibody in RA group [8.31 (5.22, 15.26) U/mL] was higher than that in non-RA group [4.50 (3.35, 5.89) U/mL] and healthy control group [3.46 (2.76, 4.92) U/mL]. The concentration of anti-CarP antibody in non-RA group was not significantly different from that in healthy control group (P=0.10). Receiver operating characteristic (ROC) curve analysis showed that the sensitivity of anti-CarP antibody in the diagnosis of RA was 58.2%, and the specificity was 93.1%. The sensitivity of the combined detection of anti-CarP antibody, anti-cyclic peptide containing citrulline (CCP) antibody and rheumatoid factor (RF) was 82.3%, and the specificity was 96.5%. The positive rate of anti-CarP antibody in serum-negative RA patients was 44.4% (20/45). Univariate Logisitic regression analysis showed that age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), RF, glucose-6-phosphate isomerase (GPI), anti-CCP antibody and anti-CarP antibody were risk factors for RA. Multivariate Logisitic regression analysis showed that anti-CCP antibody and anti-CarP antibody were independent risk factors for RA. Spearman correlation analysis showed that there was no significant correlation between anti-CarP antibody and swollen joint count (SJC), tenderness joints count (TJC), ESR, disease activity score for 28 joints (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI). The concentration of anti-CarP antibody in RA with bone erosion (n=88) was higher than that in RA without bone erosion (n=70), and there was significant difference between the two groups (P < 0.05). CONCLUSIONS: Anti-CarP antibody is an effective serological marker for the diagnosis of RA. The combined detection of RF, anti-CCP antibody and anti-CarP antibody can improve its diagnostic value, and anti-CarP antibody may be an effective assistant diagnostic tool for serum negative RA. The high serum concentration of anti-CarP antibody in patients with RA may indicate an increased risk of bone erosion and should be treated early, but further cohort studies are needed for follow-up observation.

Novel autoantibodies identified in ACPA-negative rheumatoid arthritis.

OBJECTIVES: Lack of effective biomarkers in anti-citrullinated protein antibody (ACPA)-negative rheumatoid arthritis (RA) impedes early diagnosis and treatment. This study aimed to identify novel autoantibodies in RA and verify their diagnostic values in ACPA-negative RA based on protein microarray technology. METHODS: A total of 1011 sera from 559 RA (276 ACPA-positive and 283 ACPA-negative), 239 disease controls (DCs) and 213 healthy controls (HCs) were collected and sampled on two sequential microarrays and ELISA and western blot (WB) detection, for novel autoantibodies discovery, validation and verification, respectively. The high-density protein microarray printed with a broad spectrum of recombinant human proteins was first employed to screen candidate autoantibodies, then focused microarrays composed of candidate autoantigens were used for validation, followed by ELISA and WB to verify the presence of the most promising candidates in ACPA-negative RA. RESULTS: Nine novel autoantibodies were identified by two sequential microarrays with positivity 17.93%-27.59% and specificities >90% in ACPA-negative RA. Among these, anti-PTX3 and anti-DUSP11 autoantibodies presented with the highest sensitivity and were consistently verified by ELISA and WB. Pooling samples of all cohorts, the positivities of anti-PTX3 and anti-DUSP11 in ACPA-negative RA were 27.56% and 31.80%, respectively, similar to those in ACPA-positive RA, and significantly higher than in HCs (4.69% and 2.35%) and DCs (10.04% and 8.49%) (p<0.0001). Combination of anti-PTX3 with anti-DUSP11 significantly increased the diagnostic sensitivity (38.00%) with specificity of 88.72%, regardless of ACPA status. CONCLUSION: Anti-PTX3 and anti-DUSP11 autoantibodies are newly identified biomarkers for diagnosis of ACPA-negative RA.

The amino acid variants in HLA II molecules explain the major association with adult-onset Still's disease in the Han Chinese population.

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.

Clinical features and current treatments of adult-onset Still's disease: a multicentre survey of 517 patients in China.

OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

Impact of the leucocyte immunoglobulin-like receptor A3 (LILRA3) on susceptibility and subphenotypes of systemic lupus erythematosus and Sjögren's syndrome.

BACKGROUND: Recently, our research group identified the non-deleted (functional) leucocyte immunoglobulin-like receptor A3 (LILRA3) as a new genetic risk for rheumatoid arthritis. OBJECTIVES: To further investigate whether the functional LILRA3 is a new susceptibility factor for other autoimmune diseases-for example, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). METHODS: The LILRA3 deletion polymorphism and its tagging single nucleotide polymorphism rs103294 were genotyped for 1099 patients with SLE, 403 patients with pSS and 2169 healthy controls. Association analyses were performed in whole dataset or clinical/serological subsets. The impact of LILRA3 on SLE activity and LILRA3 expression was evaluated. RESULTS: The functional LILRA3 conferred high susceptibility to both SLE (p=3.51×10(-7), OR=2.03) and pSS (p=1.40×10(-3), OR=2.32). It was associated with almost all the clinical/serological features in SLE, especially with leucopenia (p=4.09×10(-7), OR=2.19) and thrombocytopenia (p=1.68×10(-5), OR=1.70). In pSS, functional LILRA3 was specifically associated with leucopenia (p=4.39×10(-4), OR=3.25), anti-Ro/SSA-positive subphenotypes (p=4.54×10(-3), OR=2.34) and anti-La/SSB-positive subphenotypes (p=0.012, OR=2.49). Functional LILRA3 conferred higher disease activity in patients with SLE (p=0.044) and higher LILRA3 expression in both SLE (p=5.57×10(-8)) and pSS (p=1.49×10(-7)) than in controls. CONCLUSIONS: Functional LILRA3 is a new susceptibility factor for SLE and pSS. It highly predisposes to certain phenotypes such as leucopenia and thrombocytopenia in SLE, and may confer increased disease activity in SLE and a higher risk of leucopenia and autoantibody-positive subphenotypes in pSS.

[The prevalence of hyperuricemia in Xinjiang Kazaks in Fuhaii].

OBJECTIVE: to investigate the prevalence of hyperuricemia (HUA) in Kazak population in Fuhai county, Xinjiang Aletai area. METHODS: A randomized cross-sectional cluster sampling was performed in Kazaks in Fuhai. A total of 2 006 inhabitants were investigated by household survey. The questionnaires were completed for general performance, past illness history and family history. Height, weight, body mass index (BMI) and blood pressure were measured and recorded. Fasting blood samples were collected for serum uric acid and other biochemical tests. RESULTS: (1) Finally a total of 1 921 Kazaks were enrolled.The serum uric acid level in Kazaks in Fuhai was (234.11 ± 82.56) µmol/L, which was higher in males (287.48 ± 80.27) µmol/L than that in females (201.03 ± 64.74) µmol/L (P<0.001). In HUA group, serum uric acid level also had significant difference between men and women [(498.93 ± 130.24) µmol/L vs (471.20 ± 167.71) µmol/L; P = 0.044]. (2) the prevalence of HUA in Kazak general population was 2.97% (57/1 921). After standardization according to the natural population survey in 2000, the standardized rate in general group was 3.34%, in which the prevalence in males (4.76%, standardized rate was 4.64%) was higher than that in females (1.85%, standardized rate was 1.88%) (P<0.001). There was no gout found in 1 921 Kazaks in Fuhan when the study was taken. (3) Cohorts of different dietary habit ( who preferred vegetable or meat or both of them) who had drunk alcohol had higher prevalence of HUA than those with vegetarian diet without alcohol group (7.69%, 5.66% and 5.62% vs 0.78%; all P<0.05). The cohort who preferred animal food with alcohol had higher prevalence of HUA than those who preferred both vegetable and meat without alcohol (5.66% vs 5.62%; P = 0.009). (4) In men, those who had stable career, higher degree of education, regular income, had higher HUA prevalence than other cohorts. (5) people with HUA had higher plasma TC, TG, LDL, urea nitrogen and creatinine levels, higher blood pressure and higher BMI. CONCLUSION: The prevalence of HUA was lower in Kazaks in Fuhai than that in other areas in China. Males were more susceptible to HUA. diet, occupation, educational background and economic status may partly affect the prevalence of HUA in Kazaks in Fuhai.

Correlations of baseline neutrophil-lymphocyte ratio with prognosis of patients with lupus nephritis: A single-center experience.

Objective: We aimed to evaluate the correlations among the neutrophil-to-lymphocyte ratio (NLR), lupus nephritis (LN) clinical characteristics, and renal prognosis of patients with LN. Methods: We enrolled 122 patients who were diagnosed with LN at the Rheumatology Department of the People's Hospital, Xinjiang Uygur Autonomous Region from January 2013 to April 2022. We determined the occurrence of renal adverse events in patients with LN by reviewing medical records and follow-up data. Correlations were analyzed using the Spearman test, and the quartile method was applied to classify all of the 122 patients who had completed follow-up into low, medium, and high NLR groups. The Kaplan-Meier survival curve was used to conduct survival analysis, and Cox regression analyses were used to explore possible potential risk factors. Results: The baseline NLR of patients with LN was positively correlated with C-reactive protein (CRP), serum creatinine, blood urea nitrogen, and systemic lupus erythematosus disease activity index scores (P < 0.05) and negatively correlated with estimated glomerular filtration rate (eGFR) and serum albumin (P < 0.05). Patients who completed follow-up were divided into three NLR groups based on their NLR values: 30 in the low (NLR ≤ 2.21), 62 in the medium (NLR > 2.21 and NLR ≤ 6.17), and 30 in the high NLR group (NLR > 6.17). The patient survival time before developing poor renal prognosis was significantly different among the three groups (P < 0.05). High NLR (hazard ratio [HR] = 3.453, 95% confidence interval [CI]: 1.260-9.464), CRP (HR = 1.009, 95% CI: 1.002-1.017), eGFR (HR = 0.979, 95% CI: 0.963-0.995), and 24-h proteinuria values (HR = 1.237, 95% CI: 1.025-1.491) as well as anti-double stranded DNA antibody positivity (HR = 3.056, 95% CI:1.069-8.736) were independent risk factors associated with a poor renal prognosis for patients with LN. Conclusion: The baseline NLR in peripheral blood can be used as a reference index for evaluating renal function and disease activity in patients with LN, and a high NLR has predictive value for the prognosis of patients with LN.

Application of serum SERS technology combined with deep learning algorithm in the rapid diagnosis of immune diseases and chronic kidney disease.

Surface-enhanced Raman spectroscopy (SERS), as a rapid, non-invasive and reliable spectroscopic detection technique, has promising applications in disease screening and diagnosis. In this paper, an annealed silver nanoparticles/porous silicon Bragg reflector (AgNPs/PSB) composite SERS substrate with high sensitivity and strong stability was prepared by immersion plating and heat treatment using porous silicon Bragg reflector (PSB) as the substrate. The substrate combines the five deep learning algorithms of the improved AlexNet, ResNet, SqueezeNet, temporal convolutional network (TCN) and multiscale fusion convolutional neural network (MCNN). We constructed rapid screening models for patients with primary Sjögren's syndrome (pSS) and healthy controls (HC), diabetic nephropathy patients (DN) and healthy controls (HC), respectively. The results showed that the annealed AgNPs/PSB composite SERS substrates performed well in diagnosing. Among them, the MCNN model had the best classification effect in the two groups of experiments, with an accuracy rate of 94.7% and 92.0%, respectively. Previous studies have indicated that the AgNPs/PSB composite SERS substrate, combined with machine learning algorithms, has achieved promising classification results in disease diagnosis. This study shows that SERS technology based on annealed AgNPs/PSB composite substrate combined with deep learning algorithm has a greater developmental prospect and research value in the early identification and screening of immune diseases and chronic kidney disease, providing reference ideas for non-invasive and rapid clinical medical diagnosis of patients.

Raman spectroscopy combined with a support vector machine algorithm as a diagnostic technique for primary Sjögren's syndrome.

The aim of this study was to explore the feasibility of Raman spectroscopy combined with computer algorithms in the diagnosis of primary Sjögren syndrome (pSS). In this study, Raman spectra of 60 serum samples were acquired from 30 patients with pSS and 30 healthy controls (HCs). The means and standard deviations of the raw spectra of patients with pSS and HCs were calculated. Spectral features were assigned based on the literature. Principal component analysis (PCA) was used to extract the spectral features. Then, a particle swarm optimization (PSO)-support vector machine (SVM) was selected as the method of parameter optimization to rapidly classify patients with pSS and HCs. In this study, the SVM algorithm was used as the classification model, and the radial basis kernel function was selected as the kernel function. In addition, the PSO algorithm was used to establish a model for the parameter optimization method. The training set and test set were randomly divided at a ratio of 7:3. After PCA dimension reduction, the specificity, sensitivity and accuracy of the PSO-SVM model were obtained, and the results were 88.89%, 100% and 94.44%, respectively. This study showed that the combination of Raman spectroscopy and a support vector machine algorithm could be used as an effective pSS diagnosis method with broad application value.