Objective To investigate the therapeutic effects of interleukin 23p19(IL-23p19) monoclonal antibody in the MRL/lpr lupus-like mouse model. Methods A total of 36 female MRL/lpr mice aged 8 weeks were randomly divided into 6 groups: PBS group (blank control), IgG group (isotype IgG), dexamethasone (DEX) group (positive control), and three IL-23p19 monoclonal antibody treatment groups with different dose gradients: low dose (LD, 1 mg/kg), medium dose (MD, 3 mg/kg), and high dose (HD, 10 mg/kg). Drug intervention began at 12 weeks of age via tail vein injection. Urine protein levels were measured using urine protein test strips; serum anti-dsDNA antibody levels were detected by ELISA; serum creatinine and blood urea nitrogen levels were measured using an automatic biochemical analyzer; renal histopathological changes were analyzed by H&E and PAS staining; immunofluorescence was used to assess IgG and C3 immune complex deposition in kidney tissues; flow cytometry was employed to examine the expression of T helper 1(Th1), Th2, Th17, T follicular helper (Tfh), and regulatory T cells(Treg) cell subsets in the spleen; and RT-qPCR was used to detect the expression of related transcription factors in the spleen. Results IL-23p19 monoclonal antibody reduced urine protein levels, alleviated splenomegaly, improved renal function, and decreased anti-dsDNA antibody levels in MRL/lpr mice. It also mitigated glomerulonephritis and reduced renal immune complex deposition. Furthermore, IL-23p19 monoclonal antibody significantly suppressed the proportion of Th1 and Th17 cells while upregulating Treg cell proportion in the spleen. Additionally, it downregulated T-bet and retinoic acid receptor-related orphan receptor γt (RORγt) mRNA levels and upregulated forkhead box P3(FOXP3) mRNA levels in the spleen. Conclusions IL-23p19 monoclonal antibody demonstrates significant therapeutic effects in MRL/lpr mice, likely through modulation of the Th17/Treg cell balance.
Animals ; Female ; Mice, Inbred MRL lpr ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Antibodies, Monoclonal/therapeutic use* ; Interleukin-23 Subunit p19/immunology* ; Mice ; Lupus Nephritis/drug therapy* ; Kidney/drug effects* ; Antibodies, Antinuclear/blood*

Adult ; Antibodies, Antinuclear ; immunology ; Case-Control Studies ; Cross-Sectional Studies ; DNA ; blood ; immunology ; Female ; Humans ; Lupus Erythematosus, Systemic ; blood ; immunology ; Male ; Middle Aged

No abstract available.
Aged ; Antibodies, Antinuclear/analysis/*immunology ; Antiviral Agents/therapeutic use ; Fluorescent Antibody Technique ; Hepatitis C/*diagnosis/drug therapy ; Humans ; Liver Failure/diagnosis/immunology ; Male

OBJECTIVETo compare the diagnostic value of antibodies to mutated citrullinated vimentin (MCV) and some associated autoantibodies in juvenile idiopathic arthritis and to further analyze the relation between antibodies and inflammatory markers.

METHODAntibodies to cyclic citrullinated peptides (CCP) and anti-MCV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), antiperinuclear factor (APF) and antikeratin antibody (AKA) by indirect immunofluorescent assay, as well as rheumatoid factor (RF) by latex agglutination test in serum samples from 113 patients with JIA and 56 children without rheumatoid arthritis.

RESULT(1) The positive rate of anti-MCV antibodies, anti-CCP antibodies, and RF was 16.8%, 14.2%, and 21.2% in the JIA. In the other group, the positive rate was 2.2%, 2.2%, and 6.5%. There was a significant difference between the two groups (χ(2)=8.105, 6.337, 7.036, P<0.05). The positive rate of AKA and APF were not significantly different. The area under the ROC curve of anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF was 0.579, 0.561, 0.578, 0.539, 0.505. (2) The positive rate of anti-MCV antibodies and anti-CCP antibodies were higher than other antibodies. In the RF-positive polyarticular disease patients, they were higher than those in the other subtypes (P<0.05). Antibody levels were not significantly different (P>0.05) from other subtypes. (3) The swollen joint counts and tender joint counts had a low correlation to anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF. No correlation was found between ESR, CRP and anti-MCV antibodies, anti-CCP antibodies, RF, AKA and APF.

CONCLUSIONThe diagnostic value of anti-MCV antibodies is low for JIA. The positive rate of anti-MCV antibodies was higher than the other antibodies in the classification of JIA. There was a low correlation between anti-MCV antibodies, anti-CCP antibodies, RF, AKA, APF and swollen joint counts, tender joint counts.

Antibodies, Antinuclear ; blood ; Arthritis, Juvenile ; blood ; Arthritis, Rheumatoid ; Autoantibodies ; blood ; Biomarkers ; blood ; Child ; Enzyme-Linked Immunosorbent Assay ; Fluorescent Antibody Technique, Indirect ; Humans ; Peptides, Cyclic ; immunology ; ROC Curve ; Rheumatoid Factor ; blood ; Vimentin ; immunology

OBJECTIVETo evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy.

METHODSThe clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test.

RESULTSThere was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05).

CONCLUSIONSP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Adult ; Aged ; Antibodies, Antinuclear ; blood ; Antigens, Nuclear ; immunology ; Autoantibodies ; blood ; Autoantigens ; immunology ; Female ; Humans ; Liver ; pathology ; Liver Cirrhosis, Biliary ; immunology ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

OBJECTIVETo observe the effects of Xuebijing injection on dendritic cells (DCs) and T lymphocytes, and the potential mechanisms of its therapeutic effect on systemic lupus erythematosus (SLE).

METHODSA widely used mouse model, SLE-prone BLLF1 mice aged 8-10 weeks, was employed. Mice were randomly divided into 4 groups: a normal group, a model group and two treatment groups treated with Xuebijing Injection with a dose of 6.4 mL/kg via intraperitoneal administration for SLE-prone BLLF1 mice aged 8 weeks (treatment A group) and 10 weeks (treatment B group). Renal tissue sections were stained with Masson's trichrome and periodic acid-silver methenamine. Histopathological changes in the kidney were evaluated by a light microscopy. The capacity of the DCs isolated from the spleen to stimulate the T cell proliferation in response to concanavalin A (Con A) was determined.

RESULTSCompared with the model group, levels of anti-dsDNA antibodies in the two treatment groups decreased remarkablly (P<0.01, P<0.05), and levels of serum creatinine and blood urea nitrogen increased (P<0.01, P<0.05). Pathological changes were found in the kidney in the model group. Histopathological abnormalities were alleviated in the two treatment groups. Treatment with Xuebijing injection also significantly upregulated the expression of CD80, CD86 and major histocompatibility class II by DCs compared with the model group (P<0.05). When splenic T lymphocytes from BLLF1 mice were co-cultured with DCs at ratios of 1:100, 1:150 and 1:200 for 3 and 5 days, the proliferation of T lymphocytes was suppressed compared with the normal group (P<0.05), but this was restored by Xuebijing Injection under the same conditions. In the model group, levels of tumor necrosis factor (TNF)-α in supernatants were significantly elevated compared with the normal group (P<0.01), interleukin-2 levels decreased (P<0.05), while these changes were significantly alleviated in the Xuebijing treatment groups.

CONCLUSIONSXuebijing Injection alleviated renal injury in SLE-prone BLLF-1 mice. The mechanism might be through influencing T cell polarization mediated by DCs, and Xuebijing Injection might be a potential drug that suppresses immune dysfunction in patients with SLE.

Animals ; Antibodies, Antinuclear ; blood ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Concanavalin A ; pharmacology ; Dendritic Cells ; drug effects ; immunology ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Injections ; Interleukin-2 ; metabolism ; Kidney ; drug effects ; pathology ; physiopathology ; ultrastructure ; Kidney Function Tests ; Lupus Erythematosus, Systemic ; blood ; drug therapy ; immunology ; physiopathology ; Mice ; Phenotype ; T-Lymphocytes ; drug effects ; immunology ; pathology ; Tumor Necrosis Factor-alpha ; metabolism

Anti-Ro autoantibody is associated with Sjogren's syndrome (SS), systemic lupus erythematosus (SLE), and neonatal lupus syndrome (i.e., congenital complete heart block in newborns). Generally, the adult atrioventricular (AV) node is believed to be relatively resistant to the scarring effects of anti-Ro/anti-La autoantibodies. However, there have been some reports of adult complete AV block in SS and SLE patients. Here, we report a case of complete heart block in primary SS with anti-Ro autoantibodies, with no other risk factor for the development of heart block, and review their etiological association.
Antibodies, Antinuclear/*blood ; Atrioventricular Block/diagnosis/*immunology/therapy ; Cardiac Pacing, Artificial ; Electrocardiography ; Electrocardiography, Ambulatory ; Exercise Test ; Female ; Humans ; Middle Aged ; Predictive Value of Tests ; Risk Factors ; Sjogren's Syndrome/complications/*immunology ; Treatment Outcome

Retroperitoneal fibrosis (RPF) is a rare disease with unclear etiology, which is characterized by chronic non-specific inflammation of the retroperitoneum. This study was performed to investigate the clinical characteristics, laboratory findings, radiologic findings, treatment and outcome in Korean patients with RPF. We retrospectively reviewed medical records of 27 RPF patients who were admitted to Yonsei University Medical Center between 1998 and 2009. Twenty-two patients (81%) were male. The mean age at diagnosis was 56 yr. Nine patients had identifiable risk factors of RPF and three patients had combined autoimmune diseases. Acute phase reactants were elevated in most patients. Rheumatoid factor was positive in 3 of 16 patients (19%) and antinuclear antibody in 4 of 17 (24%). Five of 6 patients who were taken positron-emission tomography showed positive uptake. Glucocorticoids were used in 16 patients (59%) and four of them received combination therapy with azathioprine. After immunosuppressive treatment, the levels of acute phase reactants dropped, and the size of mass also decreased in most patients. In conclusion, the clinical characteristics of RPF in Korean patients are similar with other series except for higher proportion of male. Some patients with RPF have autoimmune features. The effect of immunosuppressive treatment on RPF is good.
Acute Disease ; Adult ; Aged ; Antibodies, Antinuclear/immunology/metabolism ; Azathioprine/therapeutic use ; Drug Therapy, Combination ; Female ; Glucocorticoids/therapeutic use ; Humans ; Immunosuppressive Agents/therapeutic use ; Male ; Middle Aged ; Positron-Emission Tomography ; Republic of Korea ; Retroperitoneal Fibrosis/*diagnosis/drug therapy/pathology ; Retrospective Studies ; Sex Factors ; Tomography, X-Ray Computed

OBJECTIVETo explore the follow-up visit, outcome and auxiliary diagnosis method on the cases with indeterminate antibody level measured by Western blotting as well as the related biological factors.

METHODSThe cases with indeterminate result were followed up according to the National Guideline for Detection of HIV/AIDS (2009) and samples were collected for HIV antibody detection, p24 antigen and nucleic acid were detected as a supplementary diagnosis at the same time. The samples were also be detected for HBV, HCV, TP, HTLV-I/II, ANA, and AFP, and the results were compared to that of screened positive and confirmed negative cases.

RESULTSA total of 73 were followed up successfully and taken a second HIV test, 25 cases were tested positive and 48 were tested negative for HIV during the follow-up period. For the 25 HIV positive cases, the HIV seroconversion rate was 100.00% at any time point when the interval between the first and returning detection was longer than 1 week. The major Western blotting bands for the cases with indeterminate result were p24 and gp160 and it was different between HIV positive and negative cases in Western blotting band profiles. The consistency and sensitivity of nucleic acid detection were higher than 90.00%, and were higher than that of p24 antigen (69.09% (38/55) and 27.27% (6/22)) (χ(2)(consistency) = 6.875, χ(2)(sensitivity) = 18.893, P < 0.05). The positive rates of ANA and AFP of indeterminate cases excluded from HIV infection were 20.83% (10/28) and 6.25% (3/48) and higher than that of screened positive and confirmed negative cases (0.00%), the difference had statistic significance (χ(2)(ANA) = 19.430, χ(2)(AFP) = 5.520, P < 0.05).

CONCLUSIONIt is critical to get timely diagnosis for the indeterminate cases according to the new national guideline for detection of HIV/AIDS. Nucleic acid detection has higher application value as auxiliary diagnosis for HIV infection than p24 antigen. The increased levels of ANA and AFP may be the factors resulting in the nonspecific indeterminate results.

Antibodies, Antinuclear ; blood ; Female ; Follow-Up Studies ; HIV Antibodies ; blood ; HIV Infections ; diagnosis ; immunology ; Humans ; Male ; alpha-Fetoproteins ; analysis

OBJECTIVETo explore the clinical and pathological features of primary biliary cirrhosis (PBC) patients with negative anti-mitochondria antibody (AMA).

METHODSTwo hundreds and eight PBC patients were enrolled. The clinical and histological data of the negative AMA cases were compared with the AMA/AMA-M2 positive cases.

RESULTS30 out of the 208 cases (14.4%) were AMA negative patients in our study. The general status, biochemical tests and histological findings between the two groups had no significant difference (P > 0.05). The Gamma-globulin, IgG, IgM and IgA levels of AMA/AMA-M2 positive PBC patients were higher than that of the AMA negative cases (P < 0.05). The abnormal rate of cholesterol in AMA negative PBC patients was 65.4% as compared to 50.4% in AMA/AMA-M2 positive cases, no significant difference existed between (P > 0.05). Anti-nuclear antibody (ANA) was observed in 29 (96.7%) AMA negative PBC patients, including 14 (48.3%) with granular pattern, 8 (27.6%) with nuclear membrane pattern, 6 (20.7%) with kinetochore pattern and 1 (3.4%) with homogeneous pattern. AMA negative PBC patients had elevated serum ALP, GGT, IgM and cholesterol levels, and decreased serum AST, IgG and IgA levels as compared with that of autoimmune hepatitis patients (P < 0.05, respectively).

CONCLUSIONIn cholestatic patients with elevated IgM and cholesterol levels, ANA positive with non-homogeneous pattern, the diagnosis of PBC should be suspected, albeit AMA negative. The clinical, biochemical and histological features of the AMA negative PBC patients were similar to classic PBC patients, but quite different from autoimmune hepatitis.

Adult ; Antibodies, Antinuclear ; analysis ; Female ; Humans ; Liver Cirrhosis, Biliary ; immunology ; pathology ; Male ; Middle Aged ; Mitochondria ; immunology ; gamma-Globulins ; metabolism