Interleukin 17E associates with haematologic involvement and autoantibody production in primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most prevalent systemic autoimmune diseases characterised by inflammation and tissue damage of exocrine glands, especially salivary or lacrimal gland. IL-17 related immune response is pathogenic with proinflammatory feature in pSS. However, whether IL-17E, an IL-17 family member, is involved in pSS pathogenesis or not, has not been determined. METHODS: Serum levels of IL-17E and IL-17A as comparison in 107 patients with pSS and 42 healthy controls were determined with multiplex cytokine assays. EULAR Sjögren's syndrome disease activity index (ESSDAI) score was calculated. Laboratory parameters were measured by standard laboratory techniques. The inflammatory infiltration of minor labial gland biopsies was graded based on numbers of lymphocyte and quantified by Focus Score (FS). Expression of IL-17E and IL-17A in the biopsy was evaluated with immunohistochemistry. RESULTS: Significantly elevated IL-17E in pSS patients associated with ESSDAI, haematologic disorders and autoantibody production, including anti-nuclear antibodies (ANA), rheumatoid factor (RF) and anti-SSA antibodies were found. Histopathological features showed that expression of IL-17E was found in labial salivary gland and correlated with lymphocytic infiltration. CONCLUSIONS: IL-17E expression in pSS patients was increased and associated with haematologic disorders, autoantibody production and lymphocytic infiltration in salivary gland. This finding indicated that IL-17E is involved in pSS pathogenesis.

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. METHODS: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. RESULTS: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. CONCLUSIONS: Low-dose IL-2 might be effective and tolerated in treatment of SLE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137).

Lipopolysaccharide-binding protein is a sensitive disease activity biomarker for rheumatoid arthritis.

OBJECTIVES: This study was performed to evaluate the performance and clinical significance of lipopolysaccharide-binding protein (LBP) as a disease activity biomarker in rheumatoid arthritis (RA). METHODS: LBP levels were measured by enzyme-linked immunosorbent assay (ELISA). The associations between LBP and the clinical and serological features of RA and its clinical significance as a RA disease activity biomarker were analysed. RESULTS: The serum level of LBP in RA was significantly elevated compared to those in OA, SLE, pSS and HC. The level of LBP in RA synovial fluid (SF) was higher than that in OA SF. LBP was significantly correlated with RA disease activity parameters such as ESR, CRP, tender joint counts, swelling joint counts and DAS28. Furthermore, LBP positive RA patients were more likely to show higher disease activity (DAS28>5.1), positive APF, interstitial lung disease and metabolic disorders. The predictive value of LBP on high disease activity was comparable with those of CRP and ESR. In 52.5% of the patients with active disease but negative in CRP /ESR, LBP was still positive and correlated with swelling joint counts. CONCLUSIONS: LBP is a sensitive serum biomarker to evaluate RA disease activity, and it could be a promising laboratory marker to assist RA disease activity assessment in active RA patients with negative ESR or CRP.

The effect of the number of conjugated C=C bonds on the ESIPT and ICT reactions of SNCN derivatives.

The electronic structure of the molecule is significantly influenced by the number of conjugated C=C bonds. In this work, the influence of the conjugated C=C bonds of the SNCN derivatives on the excited state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) properties are studied by density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculation level is proved to be reasonable by calculating electronic spectra. The hydrogen bond parameters, infrared vibrational frequency (IR), reduction density gradient (RDG) isosurface, topological analysis and potential energy curves of SNCN derivatives in ground state (S0) and the first excited state (S1) are analyzed. According to theoretical research results, ESIPT reaction has a higher likelihood of occurring in the S1 state. Moreover, the ESIPT reaction becomes more challenging to occur with the number of conjugated C=C bonds rising. Finally, the analyses of the frontier molecular orbitals (FMOs), dipole moment and charge transfer transition confirm that the ICT effect is aided by the increased number of conjugated C=C bonds. This work indicates that the number of conjugated C=C bonds can regulate the ESIPT and ICT processes, which provides guidance for the study of fluorescent groups with similar characteristics.

Substituent effects on the ESIPT process and the potential applications in materials transport field of 2'-aminochalcone derivatives.

This work investigates the different charge transfer characteristics and excited state intramolecular proton transfer process (ESIPT) of 2'-aminochalcones derivatives carrying different electron-withdrawing groups. Four new molecules are designed in the experiment and named as 2c, 3c, 4c and 5c, respectively. (Dyes and Pigments, 2022, 202.) Based on these four molecules, the effect of substituents on the ESIPT process and the charge transfer process are discussed in detail in our work. According to the study of the related parameters at the hydrogen bond site, infrared vibration spectrum, interaction region indicator isosurface (IRI) and scatter plots, it is concluded that the hydrogen bond interaction is enhanced under photoexcitation, and the descending order of the excited state hydrogen bond strength is 3c > 5c > 4c > 2c. The hydrogen bond energy is calculated by atoms in moleculs (AIM) topological analysis and core-valence bifurcation (CVB) index. The potential energy curve reveals the ESIPT mechanism. Frontier molecular orbital and electron-hole analyses explain the reasons for the changes in the ESIPT process at the electronic level. In addition, the ionization potentials (IPa and IPv), affinity energies (EAa and EAv) and reorganization energies are calculated to evaluate the potential application value of organic molecules in material transport field.

Significance of antibodies against the native ribosomal P protein complex and recombinant P0, P1, and P2 proteins in the diagnosis of Chinese patients with systemic lupus erythematosus.

BACKGROUND: This study aimed to evaluate autoantibodies against the native ribosomal P complex (anti-Rib-P(C)) and recombinant ribosomal P proteins (anti-Rib-P0, anti-Rib-P1, anti-Rib-P2) for their prevalence, diagnostic relevance and clinical associations in a Chinese cohort with systemic lupus erythematosus (SLE). METHODS: Anti-Rib-P, anti-dsDNA and anti-Smith antigen (Sm) antibodies were analyzed in sera from 198 patients with SLE, 33 with rheumatoid arthritis, 61 with Sjögren's syndrome and 70 healthy individuals by means of ELISA. RESULTS: Antibody prevalences were 29.8% (anti-Rib-P(C)), 33.3% (anti-Rib-P0), 42.9% (anti-Rib-P1) and 34.3% (anti-Rib-P2), at a specificity of 99%. Among SLE patients lacking anti-dsDNA and anti-Sm, 27.8% showed positive for at least one of the investigated anti-Rib-P types. The serological hit rate provided by anti-dsDNA/anti-Sm detection (72.7%) was increased upon parallel testing for anti-Rib-P(C) (77.3%) or anti-Rib-P0/P1/P2 (80.3%). Anti-Rib-P positivity was associated with disease activity, neuropsychiatric events, lupus nephritis, skin rash, lymphocytopenia, increased erythrocyte sedimentation rates, decreased complement C3/C4 and elevated IgA/IgG levels. CONCLUSION: Based on these results, antibodies against ribosomal P proteins are important complementary parameters to anti-dsDNA and anti-Sm, and should be considered for inclusion in the classification criteria for SLE. The diagnostic value of anti-Rib-P0/P1/P2 is diagnostically superior to that of anti-Rib-P(C).

[Significance of anti-citrullinated human papilloma virus-47 E2(345-362) peptide antibodies in diagnosis of early-stage rheumatoid arthritis].

OBJECTIVE: To investigate the prevalence and the diagnostic values of antibodies to the citrullinated HPVP in early-stage rheumatoid arthritis. METHODS: Antibodies against HPVP and citrullinated HPVP were detected by ELISA in the sera of 101 patients with early-stage RA, 149 patients with other rheumatic diseases and 40 healthy controls. The prevalence and diagnostic values of these antibodies for early-stage RA were analyzed by statistical software. RESULTS: (1)The prevalence of IgG, IgM antibodies to citrullinated HPVP in early-stage RA were significantly higher than that in the patients with other rheumatic diseases as well as in the healthy individuals.(2)The diagnostic sensitivity of IgG and IgM citrullinated HPVP antibodies in early-stage RA were 62.4% and 66.3% respectively and the specificity value of the two antibody isotypes were 88.7% and 89.6%,similar to that of the anti-CCP antibody. (3)The positivity rates of IgG and IgM antibodies against citrullinated HPVP were 59.4% and 71.9% in IgM-RF negative early-stage RA patients, and 39.4% and 51.5% in anti-CCP antibody negative early-stage RA patients. (4) The DAS28 score [ IgG (6.3±1.0) vs. (5.6±0.9), P=0.002; IgM (6.2±1.1) vs. (5.6±0.8), P=0.008] , X-ray stages (IgG 56.1% vs. 21.2%, P=0.001;IgM 50.9% vs. 29.4%, P=0.036),anti-CCP antibodies(IgG 96.8% vs. 55.3%, P=0.001; IgM 89.6% vs. 64.7%, P=0.023) in citrullinated HPVPP positive patients were higher than those of citrullinated HPVP negative patients. Additionally, the levels of ESR[IgG(70.3±32.4)vs.(51.9±27.8), P=0.004; IgM (67.4±31.5)vs.(53.8±27.7), P=0.035] in citrullinated HPVP positive patients were higher than those of negative patients (P<0.05). CONCLUSION: IgG and IgM antibodies to citrullinated HPVP are highly sensitive and specific novel biomarkers for early-stage RA diagnosis, and are related to disease activity and joint damage.

[Screening for serum specific biomarkers in patients with primary Sjögren's syndrome and interstitial lung disease using proteomic fingerprint techniques].

OBJECTIVE: To detect the serum protein biomarkers and establish a diagnostic model for primary Sjögren's syndrome (pSS) with interstitial lung disease (ILD). METHODS: Serum samples from 69 patients with pSS were prepared with WCX magnetic beads, and analyzed on PBS II-C mass spectrometer reader. Biomarker Wizard software was used to detect protein peaks and potential difference between the patients with pSS-ILD and with non-ILD. The model was developed by Biomarker Patterns software. RESULTS: Totally 7 discriminative mass-to-charge (m/z) ratios were identified to be related with pSS-ILD (P<0.05). Among these, the m/z peaks at 3 778.3, 3 318.3 and 2 236.6 were used to construct a diagnostic model. The sensitivity and specificity of the model were 93.1% and 87.5%, respectively. In a testing set, the sensitivity and specificity of the model were 84.0% and 85.7%, respectively. CONCLUSION: The potential protein biomarkers for pSS-ILD are discovered in the serum by MALDI-TOF-MS combined with WCX magnetic beads. The diagnostic pattern combining 3 778.3, 3 318.3 and 2 236.6 m/z protein peaks can discriminate pSS-ILD and non-ILD.

Mitochondrial genome sequencing with short overlapping amplicons on MiSeq FGx system.

With the development and maturation of massively parallel sequencing (MPS) technology, the mitochondrial genome (mitogenome) sequencing is increasingly applied in the forensic field. In this study, we employed the strategy of short overlapping amplicons for the whole mitogenome, library preparation with tagmentation using the Nextera® XT DNA Library Preparation Kit, sequencing on the MiSeq FGxTM Forensic Genomics System and analyzing data using the mitochondrial(mtDNA) MSR Plug-in and the mtDNA Variant Analyzer. A total of 27 libraries and 56 libraries were sequenced in a run using MiSeq Reagent Kit v2 and v3, respectively. Results showed more than 1800 × of averaged depth of coverage (DoC) at each position. Concordant haplotypes of 9947 A and 2800 M were obtained at 32 variants. Cross-reactivity was observed with 1 ng primate DNA and 10 ng non-primate DNA but could be easily distinguished. Full and accurate variants were obtained from at least 50 pg input DNA and from minor contributors between 19:1 and 1:19 mixed ratios with known reference profiles. More than 86% variants were detected from ≥200-bp degraded samples but its haplotype was assigned to more ancestral haplogroup. Further, a total of 3 962 variants were observed at 613 nucleotide positions from 103 Xibe mitogenomes with 25:1 ratio of transitions to transversions. Two new transversions (C13735A and A14755C) and two tri-alleles at nps 9824 and 16092 were identified. There were 103 unique mitogenome haplotypes from 103 Chinese Xibe that were assigned to 79 haplogroups. Haplogroup D was the preponderant top-level haplogroup in Xibe followed by F, B, M, A, N, G, C, Z, Y, HV and J. Random match probability (RMP) and haplotype diversity (HD) of the whole mitogenome was calculated as 0.0097 and 1.0000, respectively. Compared with HVS-I only, RMP decreased 33.56%, while the number of haplotypes and HD increased 15.73% and 0.49%, respectively. Principal component analysis (PCA) showed that Xibe was clustered to East and Southeast Asian. As a whole, this MPS strategy is suitable for the whole mitogenome sequencing especially for degraded samples and can facilitate generating mitogenome data to support the routine application in forensic sciences. EMP00726 is the first whole mitogenome dataset from Xibe contributed to the EMPOP. Supplemental data for this article are available online at.

Diminished natural killer T-like cells correlates with aggravated primary Sjögren's syndrome.

OBJECTIVE: To reveal the characteristics and potential role of natural killer T-like cells (NKT-like cells) in the pathogenesis of primary Sjögren's syndrome (pSS). METHODS: Forty-six patients with pSS and 30 healthy subjects were enrolled in the study. The frequencies and cell count of NKT-like cells as well as other lymphocyte subsets were analyzed by flow cytometry. The clinical and laboratory indicators of pSS patients were also collected. Then, the correlation between NKT-like cells and pSS patient manifestations was analyzed by Spearman's rank test. In addition, NKT-like cells before and after therapy were also compared. RESULTS: Both the number and the frequencies of NKT-like cells were significantly decreased in pSS patients. The counts of NKT-like cells were positively correlated with CD4+ T cells (r = 0.464, P = 0.001), CD8+ T cells (r = 0.363, P = 0.013), NK cells (r = 0.488, P = 0.001), and IgM levels (r = 0.443, P = 0.002), while negatively correlated with the disease duration (r = - 0.33, P = 0.027). Moreover, after effective therapy, NKT-like cells were recovered both in the cell counts and frequencies. CONCLUSION: In pSS, NKT-like cells were fundamentally decreased, potentially contributing to the disease pathogenesis. Modulating the status of NKT-like cells might provide a novel strategy for treating the disease. KEY POINTS: • NKT-like cells were significantly decreased in pSS patients. • NKT-like cells were correlated with pSS patient manifestations. • NKT-like cells might be serverd as a new marker for assessing the status of pSS.

"Turn-on" fluorescent probes based on Rhodamine B/amino acid derivatives for detection of Fe3+ in water.

Five kinds of Fe3+ fluorescent probes (RhB-Gly, RhB-Ala, RhB-Try, RhB-Cys, and RhB-His) were synthesized and characterized by NMR and mass spectrometry, based on the "OFF-ON" mechanism of Rhodamine B derivatives. The RhB-His based probe showed remarkable sensing performance toward the detection for Fe3+ and showed high selectivity for Fe3+ in the presence of other metal ions (such as Fe2+, Hg2+, Zn2+, Ba2+, Al3+, Co2+, Cd2+, K+, Na+, Mn2+, Pd2+, Pb2+, Ca2+, Ni2+, Cu2+, and Ag+), in PBS buffer solution (containing 2% of EtOH, pH 7.4, 1.0 mmol/L). The enhancement of the fluorescence was linearly proportional with the concentration Fe3+ (from 0 to 20 µmol/L), while the detection limit reached 0.88 µmol/L with a response time of 15 s. The RhB-His probe was successfully applied to investigate real samples and living cell imaging.

p-Pyridine BODIPY-based fluorescence probe for highly sensitive and selective detection of picric acid.

A novel fluorescence probe p-PBP for PA was synthesized based on a basic N atom as the electronic donor. The probe could detect PA over TNT, CE, PETN, RDX, HMX, NB, NT, DNT, NP, DNP, and common inorganic explosive ions (K+, Ba2+, NH4+, NO3-, ClO3-, and ClO4-), and common ions (Na+, Ca2+, and Mg2+) with high selectivity. The fluorescence quenching was attributed to the photo-induced electron transfer (PET) processes from the excited state of p-PBP to the ground state PA. The detection limit of probe p-PBP for PA was as low as 13.06 nmol/L, which is far lower than the concentration stipulated by the Environmental quality standards for surface water. The response time was less than 30 s. Hence, the fluorescence probe p-PBP was successfully developed to detect the concentration level of PA in real samples, which would provide a novel quantitative analysis method of PA in forensic science.

Double Negative B Cell Is Associated With Renal Impairment in Systemic Lupus Erythematosus and Acts as a Marker for Nephritis Remission.

Objective: Recent studies on double negative B cells (DN B cells) suggested that they have potential pathogenic roles in systemic lupus erythematosus (SLE). This study aimed to determine the circulating DN B cells in SLE patients and analyzed the clinical significance of this cell subset. Methods: Fifty-seven SLE patients and fifty healthy controls (HCs) were recruited in this study. Among the 57 SLE patients, 25 had lupus nephritis (LN). All patients were followed up for 24 weeks. Peripheral B cell subsets were analyzed by flow cytometry. Results: DN B cells were significantly elevated in the SLE patients, especially in the patients with LN (p < 0.01). DN B showed a positive correlation with 24-h urine protein excretion (24 h-UPE) levels (r = 0.444, p = 0.034) in LN patients, and inversely correlated with evaluated glomerular filtration rate (eGFR) (r = -0.351, p = 0.011). DN B cells had a positive correlation with plasma cells (r = 0.484, p < 0.001) and memory B cells (r = 0.703, p < 0.001). After treatment, decreased DN B cells were associated with LN alleviation (p = 0.002). In the follow-up, the remission rate of LN patients with decreased DN B cells was significantly higher than LN patients with increased DN B cells (83.33 vs. 25.00%, p = 0.030) at week 24. Conclusions: This study suggests that the peripheral DN B cells are positively correlated with the severity of renal damage in LN patients and may potentially be used as a prognostic marker in LN.

Evaluation of 12 different assays for detecting ANCA in Chinese patients with GPA and MPA: a multicenter study in China.

OBJECTIVE: Due to lack of comprehensive evaluation for various detection methods for antineutrophil cytoplasmic antibody (ANCA) in Chinese population, we evaluate the diagnostic performance of 12 established analysis methods in Chinese patients having granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). METHODS: Sera were collected from 209 patients with GPA or MPA and 243 diseases controls from 15 centers. Twelve different reagents were employed for C-ANCA, P-ANCA, myeloperoxidase (MPO)-ANCA, and proteinase 3(PR3)-ANCA detection. The accuracy, sensitivity, and specificity of each method were analyzed. RESULTS: The accuracy of the two indirect immunofluorescence (IIF) and two line immunoassay (LIA) was 0.838 and 0.874, 0.869, and 0.862, respectively. The accuracy of the eight quantitative antigen-specific immunoassays was varied from 0.867 to 0.967. The sensitivity of ANCA-associated vasculitis (AAV) was 0.770 and 0.761 for the two IIF, 0.727 and 0.718 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the sensitivity varied from 0.79 to 0.967. The specificity was 0.897 and 0.971 for the two IIF, 0.992 and 0.988 for the two LIAs, respectively. For the eight quantitative antigen-specific immunoassays, the specificity of AAV varied from 0.963 to 0.983. CONCLUSION: For Chinese patients suspected of having GPA and MPA, both the first-generation enzyme-linked immunosorbent assay (ELISA) and high-quality antigen-specific immunoassay can be used to detect MPO-ANCA and PR3-ANCA alone, without the combined detection with IIF to have good diagnostic performance. The chemiluminescent immunoassay (CLIA) seems to be a method worth recommending.Key points• Quantitative antigen-specific immunoassays can be used to detect MPO-ANCA and PR3-ANCA without IIF in Chinese.• CLIA has the maximum AUC value and the minimum LR (-) value, which seems to be a method worth recommending.

Anti-tubulin-α-1C autoantibody in systemic lupus erythematosus: a novel indicator of disease activity and vasculitis manifestations.

A variety of autoantibodies has been involved in the pathogenesis of systemic lupus erythematosus (SLE), some of which are well known and applied as disease biomarkers. This study aimed to determine the prevalence of a novel autoantibody, anti-tubulin-α-1C, in patients with SLE and investigate its clinical significance. Anti-tubulin-α-1C autoantibody levels were determined by enzyme-linked immunosorbent assay (ELISA) in 128 SLE patients, 38 primary Sjögren's syndrome (pSS) patients, and 106 healthy controls (HCs).White blood cell (WBC) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IgM, IgG, C3, C4, RF, ANA, dsDNA, Sm, AnuA, aCL, anti-SSA, and anti-SSB were measured by standard laboratory techniques. SLE Disease Activity Index (SLEDAI) was evaluated accordingly. Anti-tubulin-α-1C antibody levels were significantly increased in SLE patients. Elevated anti-tubulin-α-1C were correlated with higher levels of SLEDAI, increased titers of anti-Sm antibody, and decreased titers of anti-dsDNA antibody and significantly associated with cutaneous and mucosal vasculitis and milder renal involvement. Anti-tubulin-α-1C may become a novel biomarker indicative of active vasculitis in SLE and could be applied in future clinical practice.

Decreased serum thrombospondin-1 and elevation of its autoantibody are associated with multiple exacerbated clinical manifestations in systemic lupus erythematosus.

The pathological effects of thrombospondin-1 (TSP-1) have been studied in many preclinical tumor models and rheumatoid arthritis. However, the role of TSP-1 and anti-thrombospondin-1 autoantibodies (ATSA) in systemic lupus erythematosus (SLE) has not been specifically defined. In this study, we investigated the clinical relevance and functional significance of TSP-1 and ATSA in SLE patients. Serum levels of TSP-1 and ATSA were measured by ELISA in 138 adult SLE patients and 60 healthy controls. Blood cell counts, rheumatoid factor (RF), immunoglobulins, erythrocyte sedimentation rate (ESR), complements, and SLE-related autoantibodies were measured by standard laboratory techniques. Disease activity was assessed by systemic lupus erythematosus disease activity index (SLEDAI). TSP-1 concentrations were significantly lower in SLE patients compared with those in healthy controls. A significant difference of TSP-1 was observed in the patients with serositis, C3 decrease, RF positive, leukocytopenia, and thrombocytopenia. The levels of TSP-1 showed a positive correlation with the number of leukocyte and thrombocyte, while a negative correlation with anti-dsDNA antibody, IgG, ESR, and SLEDAI. ATSA was observed in 58.7% (81/138) of SLE patients, which was significantly higher than that in healthy controls (7/60, p < 0.05). Patients with active SLE showed higher ATSA positivity (67.1%) than those with inactive disease (47.1%, p < 0.05). ATSA was positively correlated with anti-rRNP antibody, IgG, total protein, and C4. This study revealed the opposite clinical relevance of TSP-1 and its autoantibody in SLE for the first time. TSP-1 may play an anti-inflammatory and immunoregulatory role in SLE autoimmunity. ATSA increased more frequently in disease-active patients and was associated with more severe clinical manifestations, which implicated its antagonistic role on TSP-1 and its involvement in the pathogenesis of SLE.

Prevalence, risk factors, and prognosis of interstitial lung disease in a large cohort of Chinese primary Sjögren syndrome patients: A case-control study.

To determine the prevalence of pulmonary complications in primary Sjögren syndrome (pSS), and to identify the risk factors and the prognosis associated with pulmonary involvement in pSS patients.A total of 1341 hospitalized patients (853 with pSS and 488 with secondary Sjögren syndrome [sSS]) were retrospectively reviewed. Of these, 165 hospitalized patients with pSS-associated interstitial lung disease (ILD) were analyzed and recruited as a study group. Eighty-four pSS patients without organ damage were included as a control group.One hundred and sixty-five patients (19.34%) from the pSS group and 126 patients (25.82%) from the sSS group presented with lung involvement. Of the 165 pSS patients with lung complications, 151 (91.5%) were women. The mean age was 61.25 ±â€Š9.79 years, and the median disease duration was 84 (24-156) months. Non-specific interstitial pneumonia (NSIP; 39.1%) was the predominant pattern on high-resolution computed tomography (HRCT). The total HRCT score was 9.71 ±â€Š4.77. Impairment in diffusion capacity was the most common (74.3%) and severe complication (predicted value of TLCO was 57.5 ±â€Š21.2%). The 5-year survival rate for all patients with pSS-ILD was 88.5%. Age, disease duration, rheumatoid factor (RF), and C-reactive protein (CRP) were significantly higher than in controls, whereas anti-SSA was less common. Age, RF, and CRP were independent predictors of ILD after adjustment for confounders.Lung involvement is a common and severe complication of Sjögren syndrome. Age and disease activity are correlated with pulmonary involvement in pSS patients.

Circulating immune complexome analysis identified anti-tubulin-α-1c as an inflammation associated autoantibody with promising diagnostic value for Behcet's Disease.

BACKGROUND: Behcet's disease (BD) is a chronic, multisystem-involved vasculitis and its pathogenesis remains elusive. No specific serological markers for BD diagnosis have been established. Identification of novel diagnostic biomarkers will be helpful in timely diagnostic and treatment for Behcet's disease. OBJECTIVE: To screen novel autoantigens or autoantibodies with potential diagnostic value in circulating immune complexes (CICs) from BD patients. METHODS: A proteomic strategy for immune complexome analysis was developed, in which CICs were separated from serum sample of 10 BD patients and 10 healthy controls and then subjected to Orbitrap mass spectrometry for autoantigen profiling. Anti-tubulin-α-1c antibody levels were further determined by enzyme-linked immunosorbent assay (ELISA) in sera of patients with BD, systemic lupus erythematosus (SLE), recurrent aphthous ulcers (RAU), ANCA associated systemic vasculitis (AASV), Takayasu's arteritis (TA) and 59 healthy controls. RESULT: A total of 17 potential antigens were identified in CICs from BD patients, but not in HC. The autoantibody to one of the identified antigens, tubulin-α-1c, was significantly increased in BD patients compared with that in healthy and disease controls. The sensitivity and specificity of tubulin-α-1c antibody in the diagnosis of BD in this study were 61.36% and 88.4%, respectively. Further analysis demonstrated that anti-tubulin-α-1c was associated with complications of deep venous thrombosis and erythema nodosum in BD. The levels of anti-tubulin-α-1c were also significantly correlated with the BD inflammation and disease activity markers ESR, CRP and BVAS. CONCLUSION: Anti-tubulin-α-1c antibody is a promising biomarker in diagnosis and severity evaluation of BD and in indicating the risk of deep venous thrombosis and erythema nodosum. The immune complexome analysis by proteomic CIC autoantigen screening is a feasible way of identifying novel biomarkers in BD.

GITRL is associated with increased autoantibody production in patients with rheumatoid arthritis.

The study aimed to determine the serum level of glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) in patients with rheumatoid arthritis (RA) and investigate its clinical significance. GITRL levels were measured by enzyme-linked immunosorbent assay (ELISA) in 88 RA patients, 20 osteoarthritis (OA) patients, and 20 healthy controls (HCs). Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were also tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies and the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The disease activity was evaluated by the 28-joint count Disease Activity Score (DAS28). GITRL concentrations were significantly elevated in both serum and synovial fluid (SF) of RA patients. GITRL levels in RA sera were significantly higher than those in matched SFs. Positive correlations were found between serum GITRL levels and inflammation parameters or autoantibody production. GITRL levels are significantly elevated in RA serum and SF and are positively correlated with autoantibody production in RA, suggesting a role of GITRL in the development of RA.

Low-dose interleukin-2 treatment selectively modulates CD4(+) T cell subsets in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a potentially life-threatening autoimmune disease characterized by altered balance of activity between effector and regulatory CD4(+) T cells. The homeostasis of CD4(+) T cell subsets is regulated by interleukin (IL)-2, and reduced production of IL-2 by T cells is observed in individuals with SLE. Here we report that treatment with low-dose recombinant human IL-2 selectively modulated the abundance of regulatory T (Treg) cells, follicular helper T (TFH) cells and IL-17-producing helper T (TH17) cells, but not TH1 or TH2 cells, accompanied by marked reductions of disease activity in patients with SLE.