INTRODUCTION: Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA) are used in the diagnosis and prognostication of rheumatoid arthritis (RA). We wanted to determine the specific contributions of RF and ACPA to the biological nature of RA and whether they act synergistically. METHODS: We identified 731 patients from our prospective multi-ethnic RA cohort and categorised them into four groups: ACPA-positive, RF-positive, doubly positive and doubly negative. We compared the demographics, Disease Activity Score-28, Health Assessment Questionnaire score, quality of life using Short Form 36 and the use of prednisolone and disease-modifying antirheumatic drugs (DMARDs) of these patient groups. RESULTS: Four hundred and ninety-one patients (67.2%) were ACPA+RF+, 54 (7.4%) were ACPA+RF-, 82 (11.2%) were ACPA-RF+ and 104 (14.2%) were ACPA-RF-. Mean disease duration before the study entry was not different in the four groups. Patients with older age of onset were less likely to be positive for RF and ACPA. Fewer ACPA+RF+ patients were in remission compared to those in the other groups ( P < 0.05). Erythrocyte sedimentation rate (ESR) was higher at study entry in the ACPA+RF+ group (40.4 mm/h vs. 30.6-30.9 mm/h, P < 0.05). Prednisolone and number of DMARDs used were higher in the ACPA+RF+ group compared to the doubly negative group. There were no differences in the functional status and quality of life. CONCLUSIONS RA patients who were positive for both ACPA and RF had lower remission rate, higher baseline ESR and required more corticosteroid and DMARD treatment compared to those who were singly positive or doubly negative. Being doubly positive confers a worse outcome to RA patients.
Humans ; Arthritis, Rheumatoid/diagnosis* ; Male ; Female ; Middle Aged ; Rheumatoid Factor/blood* ; Anti-Citrullinated Protein Antibodies/blood* ; Adult ; Quality of Life ; Prospective Studies ; Antirheumatic Agents/therapeutic use* ; Aged ; Peptides, Cyclic/immunology* ; Prednisolone/therapeutic use* ; Surveys and Questionnaires ; Severity of Illness Index ; Prognosis

Alzheimer's disease (AD) is the most common cause of dementia and is a growing public health challenge. Neuroinflammation has been proposed as a prominent pathological feature of AD and has traditionally been attributed to the innate immune system. However, emerging evidence highlights the involvement of adaptive immunity, particularly T and B lymphocytes, in the neuroinflammatory processes of AD. It remains unclear how adaptive immune responses, originally intended to protect the body, contribute to chronic inflammation and neuronal dysfunction in AD. Here, we review the roles of adaptive immunity, cellular composition, and niches and their contribution to AD development and progression. Notably, we synthesize the crosstalk between adaptive immunity and the innate immune system of the central nervous system (CNS), which is mainly mediated by glial cells and myeloid cells, and their interrelationships with amyloid-β (Aβ)/Tau pathology. We hypothesized that the alterations observed in innate immunity in AD mirror age-related immune alterations, whereas the dysregulation of adaptive immunity contributes more accurately to disease-specific immune responses. Targeting adaptive immunity in the context of neuroinflammation may provide new insights into potential therapeutic strategies designed to modulate immune responses, thereby facilitating the diagnosis, intervention, and treatment of AD.
Alzheimer Disease/metabolism* ; Humans ; Adaptive Immunity/physiology* ; Immunity, Innate/immunology* ; Animals ; Neuroinflammatory Diseases/immunology* ; Inflammation/immunology* ; Amyloid beta-Peptides/metabolism*

The innate immune response is the first line of defense for the host against viral infections. Targeted degradation of pathogenic microorganisms through autophagy, in conjunction with pattern recognition receptors synergistically inducing the production of interferon (IFN), constitutes an important pathway for the body to resist viral infections. Rubicon, a Run domain Beclin 1-interacting and cysteine-rich domain protein, has an inhibitory effect on autophagy and IFN production. On the one hand, Rubicon, as a component of the phosphoinositide 3-kinase (PI3K) complex, interacts with different domains of vacuolar protein sorting 34 (Vps34), ultraviolet radiation resistance associated gene (UVRAG), guanosine triphosphate (GTP) kinase, and RAS oncogene family member 7 (Rab7) to mediate the inhibition of autophagy maturation; on the other hand, Rubicon inhibits the ubiquitination of nuclear factor κB essential modulator (NEMO) and the dimerization of interferon regulatory factor 3 (IRF3), thereby blocking the signal transduction related to IFN production. Research has revealed that various viruses, such as Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), Sendai virus (SeV), and hepatitis C virus (HCV), achieve innate immune evasion by regulating the expression or function of Rubicon. Rubicon is expected to be a new target for antiviral therapy.
Humans ; Autophagy/immunology* ; Immunity, Innate ; Interferons/immunology* ; Immune Evasion ; Animals ; Virus Diseases/virology* ; Signal Transduction ; Viruses/immunology* ; Intracellular Signaling Peptides and Proteins/immunology* ; Autophagy-Related Proteins

The specific binding of T cell receptors (TCRs) to antigenic peptides plays a key role in the regulation and mediation of the immune process and provides an essential basis for the development of tumour vaccines. In recent years, studies have mainly focused on TCR prediction of major histocompatibility complex (MHC) class I antigens, but TCR prediction of MHC class II antigens has not been sufficiently investigated and there is still much room for improvement. In this study, the combination of MHC class II antigen peptide and TCR prediction was investigated using the ProtT5 grand model to explore its feature extraction capability. In addition, the model was fine-tuned to retain the underlying features of the model, and a feed-forward neural network structure was constructed for fusion to achieve the prediction model. The experimental results showed that the method proposed in this study performed better than the traditional methods, with a prediction accuracy of 0.96 and an AUC of 0.93, which verifies the effectiveness of the model proposed in this paper.
Receptors, Antigen, T-Cell/immunology* ; Histocompatibility Antigens Class II/metabolism* ; Humans ; Neural Networks, Computer ; Peptides/metabolism* ; Protein Binding

OBJECTIVE: To investigate the effect of chidamide on the killing activity of NK (Natural killer cell, NK) cells targeting K562 cells and its related mechanism. METHODS: K562 cells were pretreated with chidamide at different concentrations and cocultured with NK cells at different effect-target ratios. The killing effect of chidamide on K562 cells by NK cells, the expression of natural killer group 2 member D (NKG2D) ligands and apoptosis rate of K562 cells were detected by flow cytometry. RESULTS: The killing sensitivity of NK cells to K562 cells could be enhanced by chidamide. The expression of ULBP2 on K562 cell surface could be up-regulate, however, the expression of ULBP1 and MICA/MICB showed no statistically difference as compared with control group. Chidamide showed no obvious cytotoxicity to K562 cells. CONCLUSION Chidamide can significantly improve killing efficiency of NK cells on K562 cells, which may be related to the up-regulation of ULBP2 expression.
Aminopyridines ; Benzamides ; GPI-Linked Proteins ; Histocompatibility Antigens Class I ; Humans ; Intercellular Signaling Peptides and Proteins ; K562 Cells ; Killer Cells, Natural ; immunology ; NK Cell Lectin-Like Receptor Subfamily K

Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.
Animals ; Chemical and Drug Induced Liver Injury ; etiology ; immunology ; Chemokine CCL2 ; genetics ; immunology ; Diterpenes ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Epoxy Compounds ; adverse effects ; Female ; Humans ; Interleukin-6 ; genetics ; immunology ; Intracellular Signaling Peptides and Proteins ; genetics ; immunology ; Liver ; drug effects ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; immunology ; Phenanthrenes ; adverse effects ; Tripterygium ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVE: To investigate the clinical characteristics of rheumatoid arthritis (RA) patients with malignant tumor. METHODS: Retrospective summary was made of 1 562 in patients of RA from January 2011 to June 2017. In the study, 74 RA patients with malignant tumor were reviewed and analyzed, and the general conditions, tumor types, RA and tumor onset sequence, and the medication situation were analyzed. RESULTS: The incidence of malignant tumor in the patients with rheumatoid arthritis in our center was 4.16%. The 74 patients were complicated with malignant tumor, of whom 53 were female, and 21 male. The age of RA at presentation was (52.6±17.8) years. The average disease duration of malignant tumor was (63.4 ± 12.7) years. The onset time of rheumatoid arthritis was earlier than that of malignant tumors in 51 cases (51/74), with an average of (17.2±14.2) years between 2 and 60 years. The incidence of malignant tumor was earlier than that of rheumatoid arthritis in 16 cases (16/74), with an average of (6.2±5.9) years between 1 and 21 years, of which 10 cases were sex hormone related tumors. Seven cases (7/74) were diagnosed with RA at the same time, and the time interval between the two diseases was within 1 year. All the patients were over 60 years old with digestive tract tumors. All the 7 patients showed polyarthritis, significantly increased erythrocyte sedimentation rate and C-reactive protein, including 4 rheumatoid factor positive cases and 2 anti-CCP antibody positive cases. The effect of non-steroidal anti-inflammatory drugs and traditional drugs to improve the condition of the disease was poor in the 7 patients, and the condition was relieved after using low-dose glucocorticoids. Gastrointestinal tumors, breast and reproductive system tumors were the most common, followed by respiratory, urological and blood system tumors. CONCLUSION The risk in patients of rheumatoid arthritis complicated with malignant tumor is higher than that of the general population. A variety of factors play an important role in cancer risk of RA, including disease activity, some estrogen metabolites, the use of drugs and so on. Therefore, all RA patients should be screened for malignant tumor during diagnosis, and malignant tumor surveillance is mandatory for all rheumatoid arthritis patients after diagnosis.
Adult ; Aged ; Arthritis, Rheumatoid/complications* ; Autoantibodies ; C-Reactive Protein/analysis* ; Female ; Humans ; Male ; Middle Aged ; Neoplasms/immunology* ; Peptides, Cyclic ; Retrospective Studies ; Rheumatoid Factor/blood*

Herbal extracts have been extensively used worldwide for their application on memory improvement, especially among aged and memory-deficit populations. In the present study, the memory loss induced by human Abeta protein over-expression in fruitfly Alzheimer's disease (AD) model was rescued by multiple extracts from Gardenia jasminoides. Three extracts that rich with gardenia yellow, geniposide, and gardenoside components showed distinct rescue effect on memory loss. Further investigation on adding gardenoside into a formula of Ganoderma lucidum, Panax notoginseng and Panax ginseng (GPP) also support its therapeutic effects on memory improvement. Interestingly, the application of GPP and gardenoside did not alter the accumulation of Abeta proteins but suppressed the expression of immune-related genes in the brain. These results revealed the importance and relevancy of anti-inflammation process and the underlying mechanisms on rescuing memory deficits, suggesting the potential therapeutic use of the improved GPP formulation in improving cognition in defined population in the future.
Alzheimer Disease ; drug therapy ; Animals ; Antimicrobial Cationic Peptides ; genetics ; Brain ; drug effects ; immunology ; Cognition ; drug effects ; Disease Models, Animal ; Drosophila ; Drosophila Proteins ; genetics ; Gardenia ; chemistry ; Gene Expression Regulation ; drug effects ; Immunity, Innate ; drug effects ; Iridoids ; chemistry ; isolation & purification ; pharmacology ; Plant Extracts ; chemistry ; isolation & purification ; pharmacology ; Polymerase Chain Reaction

BACKGROUNDSmD1-amino-acid 83-119 peptide (SmD183-119) is the major epitope of Smith (Sm) antigen, which is specific for adult systemic lupus erythematosus (SLE). The anti-SmD183-119 antibody has exhibited higher sensitivity and specificity than anti-Sm antibody in diagnosing adult SLE. However, the utility of anti-SmD183-119antibodies remains unclear in children with SLE (cSLE). This study aimed to assess the characteristics of anti-SmD183-119antibody in the diagnosis of cSLE.

METHODSSamples from 242 children with different rheumatological and immunological disorders, including autoimmune diseases (SLE [n = 46] and ankylosing spondylitis [AS, n = 11]), nonautoimmune diseases (Henoch-Schonlein purpura [HSP, n = 60], idiopathic thrombocytopenia purpura [n = 27], hematuria [n = 59], and arthralgia [n = 39]) were collected from Shanghai Children's Medical Center from March 6, 2012 to February 27, 2014. Seventy age- and sex-matched patients were enrolled in this study as the negative controls. All the patients' sera were analyzed for the anti-SmD183-119, anti-Sm, anti-U1-nRNP, anti-double-stranded DNA (dsDNA), anti-nucleosome, anti-SSA/Ro60, anti-SSA/Ro52, anti-SSB, anti-Scl-70, and anti-histone antibodies using the immunoblotting assay. The differences in sensitivity and specificity between anti-SmD183-119 and anti-Sm antibodies were compared by Chi-square test. The correlations between anti-SmD183-119and other auto-antibodies were analyzed using the Spearman's correlation analysis. A value of P< 0.05 was considered statistically significant.

RESULTSThirty-six out of 46 patients with cSLE were found to be positive for anti-SmD183-119, while 12 patients from the cSLE cohort were found to be positive for anti-Sm. Compared to cSLE, it has been shown that anti-SmD183-119 was only detected in 27.3% of patients with AS and 16.7% of patients with HSP. In comparison with anti-Sm, it has been demonstrated that anti-SmD183-119 had a higher sensitivity (78.3% vs. 26.1%, χ2 = 25.1, P< 0.05) and a lower specificity (90.8% vs. 100%, χ2 = 13.6, P< 0.05) in the diagnosis of cSLE. Further analysis revealed that anti-SmD183-119antibodies were positively correlated with anti-dsDNA, anti-nucleosome, and anti-histone antibodies in cSLE. Moreover, it has been clearly shown that anti-SmD183-119 was more sensitive than anti-Sm in discriminating autoimmune diseases from nonautoimmune disorders in patients with arthralgia or hematuria.

CONCLUSIONSMeasurement of anti-SmD183-119in patients with cSLE has a higher sensitivity and a marginally lower specificity than anti-Sm. It has been suggested that inclusion of anti-SmD183-119testing in the integrated laboratory diagnosis of cSLE may significantly improve the overall sensitivity in child populations.

Autoantibodies ; immunology ; Autoantigens ; immunology ; Child ; Female ; Humans ; Immune System Diseases ; immunology ; Immunoblotting ; Lupus Erythematosus, Systemic ; immunology ; Male ; Peptides ; chemistry ; immunology ; snRNP Core Proteins ; immunology

Swine influenza viruses (SwIVs) cause considerable morbidity and mortality in domestic pigs, resulting in a significant economic burden. Moreover, pigs have been considered to be a possible mixing vessel in which novel strains loom. Here, we developed and evaluated a novel M2e-multiple antigenic peptide (M2e-MAP) as a supplemental antigen for inactivated H3N2 vaccine to provide cross-protection against two main subtypes of SwIVs, H1N1 and H3N2. The novel tetra-branched MAP was constructed by fusing four copies of M2e to one copy of foreign T helper cell epitopes. A high-yield reassortant H3N2 virus was generated by plasmid based reverse genetics. The efficacy of the novel H3N2 inactivated vaccines with or without M2e-MAP supplementation was evaluated in a mouse model. M2e-MAP conjugated vaccine induced strong antibody responses in mice. Complete protection against the heterologous swine H1N1 virus was observed in mice vaccinated with M2e-MAP combined vaccine. Moreover, this novel peptide confers protection against lethal challenge of A/Puerto Rico/8/34 (H1N1). Taken together, our results suggest the combined immunization of reassortant inactivated H3N2 vaccine and the novel M2e-MAP provided cross-protection against swine and human viruses and may serve as a promising approach for influenza vaccine development.
Animals ; Antibodies, Viral/blood ; Antigens, Viral/genetics/*immunology ; Body Weight ; Cross Protection/*immunology ; Disease Models, Animal ; Epitopes, T-Lymphocyte/genetics/immunology ; Female ; Influenza A Virus, H3N2 Subtype/genetics/*immunology ; Influenza Vaccines/*immunology ; Mice ; Mice, Inbred BALB C ; Orthomyxoviridae Infections/*immunology/mortality/pathology/prevention & control ; Peptides/genetics/*immunology ; Random Allocation ; Survival Analysis ; Vaccines, Synthetic/immunology ; Virus Replication