BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune prothrombotic condition with significant morbidity. The objective of this study was to identify additional clinical and epidemiological risks of arterial thrombosis, venous thrombosis, and pregnancy morbidities in a large cohort of persistent antiphospholipid antibodies (aPLs)-positive carriers. METHODS: This was a cross-sectional cohort study of 453 consecutive patients with a documented positive aPL who attended Peking University People's Hospital. Among 453 patients screened, 297 patients had persistent positive aPL. We compared asymptomatic aPL carriers with thrombotic and obstetric APS patients. And the univariate analysis and multivariable logistic regression were used to evaluate the association between different risk factors and APS clinical manifestations. The levels of circulating markers of neutrophil extracellular traps (NETs) (cell-free DNA and citrullinated histone H3 [Cit-H3]) were assessed and compared among aPL-positive carriers with or without autoimmune disease and APS patients. RESULTS: Additional risk factors associated with arterial thrombosis among aPL-positive carriers included: smoking (odds ratio [OR] = 6.137, 95% confidence interval [CI] = 2.408-15.637, P  = 0.0001), hypertension (OR = 2.368, 95% CI = 1.249-4.491, P  = 0.008), and the presence of underlying autoimmune disease (OR = 4.401, 95% CI = 2.387-8.113, P < 0.001). Additional risks associated with venous thrombosis among aPL carriers included: smoking (OR = 4.594, 95% CI = 1.681-12.553, P  = 0.029) and the presence of underlying autoimmune disease (OR = 6.330, 95% CI = 3.355-11.940, P < 0.001). The presence of underlying autoimmune disease (OR = 3.301, 95% CI = 1.407-7.744, P  = 0.006) is the additional risk, which demonstrated a significant association with APS pregnancy morbidity. Higher circulating levels of cell-free DNA and Cit-H3 were observed among APS patients and aPL patients with autoimmune diseases compared with those aPL carriers without underlying autoimmune diseases. Furthermore, control neutrophils that are conditioned with APS patients'sera have more pronounced NET release compared with those treated with aPL carriers'sera without underlying autoimmune diseases. CONCLUSIONS We identified several potential additional risk factors for APS clinical manifestations among a large cohort of Chinese aPL carriers. Our data may help physicians to risk stratify aPL-positive Asian patients.
Antibodies, Antiphospholipid ; Antiphospholipid Syndrome/complications* ; Autoimmune Diseases ; Cell-Free Nucleic Acids ; Cohort Studies ; Cross-Sectional Studies ; Female ; Humans ; Morbidity ; Pregnancy ; Risk Factors ; Thrombosis/etiology*

Adult ; Asymptomatic Diseases/epidemiology* ; Autoimmune Diseases/etiology* ; China/epidemiology* ; Female ; Humans ; Hypothyroidism/etiology* ; Male ; Metabolic Syndrome/epidemiology* ; Middle Aged ; Obesity/epidemiology* ; Risk Factors ; Thyroid Diseases/etiology* ; Young Adult

Objective: To investigate the role of mast cells in chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS). METHODS: Forty-five male SD rats were equally randomized into a control, an experimental autoimmune prostatitis (EAP) model, and an intervention group. The EAP model was made in the latter two groups by subcutaneous injection of mixed suspension of complete Freund's adjuvant and prostate tissue, while the controls were treated subcutaneously with 0.9% sodium chloride. Tactile allodynia was quantified in the pelvic region of the control and EAP animals using Von-Frey filaments at 5, 10, 20, 30 and 40 days. After successful establishment of the EAP model, the rats of the intervention group were injected intraperitonieally with cromolyn sodium for 10 days, and meanwhile tactile allodynia was detected in the rats of the intervention and EAP model groups every other day. Then the prostates of the rats were harvested for HE and toluidine blue staining and measurement of the expression of mast cell tryptase by immunohistochemistry and Western blot. RESULTS: Von-Frey assessment showed a more severe pelvic pain in the EAP model than in the control rats, but milder in the intervention group than in the EAP models. HE staining revealed infiltration of lymphocytes and neutrophils in the prostate and congestion surrounding the gland in the EAP model rats, but none in the controls. However, both the infiltration and congestion were significantly alleviated in the intervention group. Toluidine blue staining shown that. Compared with the control group, the total count of mast cells and the number degranulated mast cells were markedly increased in the EAP models (P <0.01) but decreased in the intervention group (P <0.05). Both immunohistochemistry and Western blot manifested that the expression of tryptase in the mast cells was remarkably upregulated in the EAP (both P <0.01) but down-regulated in the intervention group (P <0.05 and P <0.01). CONCLUSIONS Both the total count of mast cells and the number of degranulated mast cells are significantly increased in the prostate of EAP rats. Mast cells are one of the most important mediators of type Ⅲ prostatitis-induced chronic pelvic pain, which can be used as a target for the intervention and treatment of type Ⅲ prostatitis.
Adjuvants, Immunologic ; Animals ; Autoimmune Diseases ; etiology ; pathology ; Cell Degranulation ; Chronic Disease ; Chronic Pain ; etiology ; Disease Models, Animal ; Freund's Adjuvant ; Male ; Mast Cells ; enzymology ; physiology ; Pelvic Pain ; etiology ; Prostatitis ; etiology ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tryptases ; metabolism

Interleukin-21 (IL-21) is a new member of the interleukin-2 family. It is mainly synthesized and secreted by the activated of CD4(+) T cells and natural killer T cells. IL-21 receptor (IL-21R) is mainly expressed in T cells, B cells, and natural killer (NK) cells. After binding to its receptor, IL-21 can regulate the activation and proliferation of T cells, B cells, and NK cells through activating JAKs-STATs signaling pathways. As a new immunoregulatory factor, IL-21 and its receptor play important roles in the development and progression of various autoimmune diseases. Regulation of the expression levels of IL-21 and IL-21R and blocking of their signal transduction pathways with blockers may be new treatment options for autoimmune diseases.
Animals ; Autoimmune Diseases ; etiology ; immunology ; Dendritic Cells ; immunology ; Humans ; Interleukins ; physiology ; Killer Cells, Natural ; immunology ; Lymphocytes ; immunology ; Receptors, Interleukin-21 ; physiology

Chronic prostatitis is a highly prevalent disease of unclear etiology. Researches show that autoimmune reaction is one cause of the problem. An effective animal model may help a lot to understand the pathogenesis and find proper diagnostic and therapeutic strategies of the disease. Currently used autoimmune prostatitis-related animal models include those of age-dependent spontaneous prostatitis, autoimmune regulator-dependent spontaneous prostatitis, self antigen-induced prostatitis, and steroid-induced prostatitis. Whether an animal model of autoimmune prostatitis is successfully established can be evaluated mainly from the five aspects: histology, morphology, specific antigens, inflammatory factors, and pain intensity.
Animals ; Autoimmune Diseases ; etiology ; pathology ; Chronic Disease ; Disease Models, Animal ; Humans ; Male ; Prostatitis ; etiology ; immunology ; pathology ; Transcription Factors

The purpose of this study was to investigate the etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population. The clinical data of 142 patients with chronic pancreatitis were retrospectively studied. All patients were of Chinese nationality and hospitalized from January 2008 to December 2011. Their ages ranged from 14 to 76 years, with a mean of 43 years. Of 142 patients, there were 72 cases of obstructive chronic pancreatitis (50.70%), 19 cases of alcoholic chronic pancreatitis (13.38%), 14 cases of autoimmune pancreatitis (9.86%) and 37 cases of undetermined etiology (26.06%). Pathologically, the average inflammatory mass diameter was 3.8 ± 3.3 cm, biliary obstruction occurred in 36 cases, gall stones in 70 cases, calcification in 88 cases, ductal dilatation in 61 cases, side branch dilatation in 32 cases, ductal irregularity in 10 cases, lymphocytic inflammation in 23 cases, obliterative phlebitis in 14 cases, extra pancreatic lesion in 19 cases and fibrosis in 142 cases. Location of pancreatic lesion in the region of head (n=97), neck (n=16), body (n=12), tail (n=15) and whole pancreas (n=2) influenced the choice of surgical procedures. Ninety-four patients (66.20%) received surgical treatment and 33.80% received other treatments. After operation, 80.85% of 94 patients experienced decreased pain, and 8.51% of 94 showed recovery of endocrine function but with a complication rate of 12.77%. All the operations were performed successfully. According to the pain scale of European Organization for Research and Treatment of Cancer (QLQ-C30) a decrease from 76 ± 22 to 14 ± 18 was observed. Etiology, pathological characteristics, management and prognosis of chronic pancreatitis in the Chinese population vary from others.
Adolescent ; Adult ; Aged ; Autoimmune Diseases ; epidemiology ; therapy ; China ; epidemiology ; Cholestasis ; epidemiology ; therapy ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis, Alcoholic ; epidemiology ; therapy ; Pancreatitis, Chronic ; etiology ; pathology ; therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult

No abstract available.
Autoimmune Diseases/etiology ; Female ; Humans ; Multiple Sclerosis/etiology ; Papillomavirus Infections/*prevention & control ; Papillomavirus Vaccines/*adverse effects/*immunology ; Uterine Cervical Neoplasms/prevention & control

BACKGROUND/AIMS: Azathioprine (AZA) has been widely used in the therapy of inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH). However, studies evaluating the adverse effects of AZA in these two diseases are lacking. The aim of this study was to compare the adverse effects of AZA in Korean IBD and AIH patients. METHODS: Patients with IBD or AIH who were treated with AZA at Keimyung University Dongsan Medical Center (Daegu, Korea) between January 2002 and March 2011 were enrolled. Their medical records were reviewed retrospectively in terms of clinical characteristics and adverse effects of AZA. RESULTS: A total of 139 IBD patients and 55 AIH patients were finally enrolled. Thirty IBD patients (21.6%) and eight AIH patients (14.5%) experienced adverse effects of AZA. In particular, the prevalence of leukopenia was significantly higher in the IBD group than in the AIH group (p=0.026). T474C mutation was observed in three of 10 patients who were assessed for thiopurine methyltransferase (TPMT) genotype. CONCLUSIONS: IBD patients are at increased risk for the adverse effects of AZA compared with AIH patients, of which leukopenia was the most commonly observed. Therefore, IBD patients receiving AZA therapy should be carefully monitored.
Adolescent ; Adult ; Aged ; Azathioprine/adverse effects/*therapeutic use ; Base Sequence ; Female ; Genotype ; Hepatitis, Autoimmune/*drug therapy ; Humans ; Immunosuppressive Agents/adverse effects/*therapeutic use ; Inflammatory Bowel Diseases/*drug therapy ; Leukopenia/epidemiology/etiology ; Male ; Methyltransferases/chemistry/genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Republic of Korea ; Retrospective Studies ; Young Adult

Autoimmune Diseases ; diagnosis ; etiology ; therapy ; Child, Preschool ; Encephalitis ; diagnosis ; etiology ; therapy ; Female ; Humans ; Receptors, N-Methyl-D-Aspartate ; immunology

OBJECTIVETo investigate the clinical features and mechanisms of hepatitis B virus (HBV) reactivation induced by chemotherapy or immunosuppressive therapy and subsequent fulminant hepatic failure (FHF) in patients with autoimmune diseases.

METHODSSeven cases of FHF related to HBV reactivation were retrospectively assessed. All patients had been confirmed as hepatitis B e antigen (HBeAg) seronegative and had undergone glucocorticoid-based therapy to manage primary diseases, including nephrotic syndrome (2 cases), polycystic kidney disease combined with chronic nephritis (1 case), conditions following kidney transplantation (1 case), lymphadenoma (1 case), idiopathic thrombocytopenic purpura (1 case), and angitis (1 case). Levels of sero-markers of HBV and HBV DNA were recorded. Serum samples from patients were respectively applied to HepG2.2.15 and HepG2 cell lines in order to investigate the effects on cell proliferation (by MTT assay) and apoptosis (by Hoechst 33342 staining assay). Intergroup differences were statistically assessed by the t-test.

RESULTSFor all patients, the initial clinical signs of hepatic failure emerged at 4 to 11 months after receipt of the glucocorticoid treatment. At the time of hepatic failure, HBeAg seropositivity was detected in 4 patients, including one patient who also showed seropositivity for the hepatitis B surface antibody (HBsAb). All 7 patients showed high levels of HBV DNA when the hepatitis condition flared. Neither remedial antiviral treatments nor internal medicine comprehensive treatments, including therapeutic plasma exchange, were effective in any of these cases. The duration from clinical signs onset to death ranged from 24 to 47 days. Treatment of HepG2.2.15 and HepG2 cells with serum samples from patients with FHF showed a dosage-effect relationship of the serum concentration on the cellular proliferation inhibition rate, with the serum of patients with FHF having more severe inhibiting effects on the HepG2.2.15 cells than on the HepG2 cells. The HepG2.2.15 cells showed a greater tendency towards apoptosis upon treatment with serum samples from patients with FHF, compared to the HepG2 cells.

CONCLUSIONHBV reactivation induced by chemotherapy or immunosuppressive therapy is a problem currently encountered in the management of malignancies or rheumatic autoimmune disease patients. It is critical to verify HBV status prior to initiation of these treatment strategies so that appropriate antiviral prophylaxis may be administered, so as to reduce the risk of HBV reactivation and subsequent repression of cell proliferation and apoptosis that can promote development of FHF and increase a patient's risk of death.

Adult ; Aged ; Apoptosis ; Autoimmune Diseases ; complications ; Cell Proliferation ; Female ; Glucocorticoids ; adverse effects ; therapeutic use ; Hep G2 Cells ; Hepatitis B ; complications ; virology ; Hepatitis B virus ; drug effects ; Humans ; Liver Failure ; etiology ; virology ; Male ; Middle Aged ; Retrospective Studies ; Virus Activation ; drug effects