OBJECTIVE: To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages. METHODS: In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table. RESULTS: Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both <i>Pi> < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (<i>Pi>>0.05). After adjusting with anticardiolipin antibodies, anti-β₂ glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (<i>ORi>=2.084, 95%<i>CIi> 1.045-4.155, <i>Pi> < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (<i>ORi>=2.368, 95%<i>CIi> 1.187-4.722, <i>Pi> < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%. CONCLUSION Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.
Pregnancy ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Prothrombin ; Retrospective Studies ; Phosphatidylserines ; Prospective Studies ; beta 2-Glycoprotein I ; Antibodies, Antiphospholipid ; Antiphospholipid Syndrome/diagnosis* ; Antibodies, Anticardiolipin ; Abortion, Habitual ; Immunoglobulin G ; Immunoglobulin M

To evaluate the data obtained from the external quality assurance program initiated by Chinese Rheumatism Data Center (CRDC-QAP) for autoantibodies detection in 2021, so as to assess the consensus and differences in cross-laboratory testing to autoantibodies in China. This is a retrospective study. After collecting data from the first half year (from May 15th to July 10th) and the second half year (from August 15th to November 19th) of CRDC-QAP program for autoantibody detection in 2021, it firstly analyzed the qualitative consensus of the cross-laboratory results. Secondly, it compared the positivity grade of numeric results according to the Sample to cut-off ratio (S/CO ratio) calculation. Finally, the mean and coefficient variation (<i>CVi>) of numeric results from three major manufacturers were calculated. A total of 303 and 332 clinical labs voluntarily participated in the first half year and the second half year of CRDC-QAP program for autoantibody detection in 2021, respectively. Except for anti-β2 glycoprotein type I (aβ2-GPI) IgM, the cross-laboratory consensus of qualitative results for the other autoantibodies is greater than 96%. As for anti-cyclic citrullinated peptide antibody (anti-CCP) and anti mitochondrial antibody-M2 (AMA-M2), the numeric results from more than 90% laboratories showed the same positivity grade. More than 50% of laboratories used chemiluminescence immunoassay (CLIA) for quantitative evaluation of autoantibody. The CV of numeric results from different manufacturers showed certain differences(<i>Pi><0.01) with the range from 0 to 238%. Although high consensus can be observed in term of qualitative result for autoantibody detection in cross-laboratory, there are still certain differences in numeric results in term of positivity grade and manufacturer-based CV.
Humans ; Autoantibodies ; Antibodies, Anticardiolipin/analysis* ; Retrospective Studies ; East Asian People ; beta 2-Glycoprotein I ; Rheumatic Diseases

OBJECTIVE: To investigate the significance and distribution of oxidized low-density lipoprotein antibodies (ox-LDL-Ab) in patients with antiphospholipid syndrome (APS). METHODS: In this study, 334 patients who were hospitalized in the Department of Rheumatology and Immunology, Peking University People's Hospital were included. There were 162 APS patients, 122 patients with other autoimmune diseases without thrombosis or obstetric disease as disease control and 50 healthy controls. The clinical data and laboratory indicators were retrospectively collected. The ox-LDL-Ab, anticardiolipin (aCL) IgG/IgA/IgM, and anti-β2-glycoprotein Ⅰ (aβ2GPI) IgG/IgA/IgM were detected by enzyme-linked immunosorbent assay (ELISA). The relationship between ox-LDL-Ab and clinical and laboratory parameters were analyzed by SPSS 27.0. RESULTS: In APS group, 60.5% of patients had thrombosis, 48.1% had pregnancy morbidity, 34.0% had thrombocytopenia. The positive rates of aCL, aβ2GPI and lupus anticoagulant (LAC) were 17.9%, 34.6%, and 46.9%, respectively. The ox-LDL-Ab titers and positive rate in APS group were higher than that in healthy controls [titers: 40.8 (25.4-66.0) U/mL <i>vs.i> 24.1 (12.3-36.5) U/mL, <i>Pi>=0.001; positive rate: 67.3% <i>vs.i> 36.0%, <i>Pi>=0.001]. The diffe-rences in titers and positive rate of ox-LDL-Ab between APS patients and disease controls were not statistically significant [titers: 40.8 (25.4-66.0) U/mL <i>vsi>. 35.9 (24.2-53.1) U/mL, <i>Pi>=0.118; positive rate: 67.3% <i>vs.i> 61.5%, <i>Pi>=0.318]. The area under curve (AUC) for aβ2GPI, aCL, and ox-LDL-Ab were 0.745 (95%<i>CIi>: 0.692-0.797), 0.666 (95%<i>CIi>: 0.608-0.724), 0.609 (95%<i>CIi>: 0.549-0.669), respectively. The Youden's index was 0.388, 0.269, and 0.132, respectively. The AUC for ox-LDL-Ab in seronegative APS patients was 0.562 (95%<i>CIi>: 0.480-0.645). The sensitivity and specificity of ox-LDL-Ab in seronegative APS patients were 63.9% and 47.0%, respectively, and the Youden's index was 0.109. The ox-LDL-Ab positive group had higher positive rate of aβ2GPI (42.2% <i>vsi>. 18.9%, <i>Pi>=0.003) and aCL (22.9% <i>vsi>. 7.5%, <i>Pi>=0.017) than the ox-LDL-Ab negative group. There was no correlation between ox-LDL-Ab and thrombosis, coronary artery disease, pregnancy morbidity, hyperlipidemia, hypocomplementemia, and LAC positivity. CONCLUSION Ox-LDL-Ab was correlated with aCL and aβ2GPI, and no association were observed between ox-LDL-Ab and thrombosis, coronary artery disease, and pregnancy morbidity.
Pregnancy ; Female ; Humans ; Antiphospholipid Syndrome ; Antibodies, Anticardiolipin ; Retrospective Studies ; Coronary Artery Disease ; Clinical Relevance ; beta 2-Glycoprotein I ; Lupus Coagulation Inhibitor ; Lipoproteins, LDL ; Autoantibodies ; Immunoglobulin G ; Immunoglobulin A ; Thrombosis ; Immunoglobulin M

PURPOSE: Atherosclerosis is classically defined as an immune-mediated disease characterized by accumulation of low-density lipoprotein cholesterol over intima in medium sized and large arteries. Recent studies have demonstrated that both innate and adaptive immune responses are involved in atherosclerosis. In addition, experimental and human models have recognized many autoantigens in pathophysiology of this disease. Oxidized low-density lipoproteins, beta2 glycoprotein I (beta-2-GPI), and heat shock protein 60 (HSP60) are the best studied of them which can represent promising approach to design worthwhile vaccines for modulation of atherosclerosis. MATERIALS AND METHODS: In silico approaches are the best tools for design and evaluation of the vaccines before initiating the experimental study. In this study, we identified immunogenic epitopes of HSP60, ApoB-100, and beta-2-GPI as major antigens to construct a chimeric protein through bioinformatics tools. Additionally, we have evaluated physico-chemical properties, structures, stability, MHC binding properties, humoral and cellular immune responses, and allergenicity of this chimeric protein by means of bioinformatics tools and servers. RESULTS: Validation results indicated that 89.1% residues locate in favorite or additional allowed region of Ramachandran plot. Also, based on Ramachandran plot analysis this protein could be classified as a stable fusion protein. In addition, the epitopes in the chimeric protein had strong potential to induce both the B-cell and T-cell mediated immune responses. CONCLUSION: Our results supported that this chimeric vaccine could be effectively utilized as a multivalent vaccine for prevention and modulation of atherosclerosis.
Apolipoprotein B-100 ; Arteries ; Atherosclerosis* ; Autoantigens ; B-Lymphocytes ; beta 2-Glycoprotein I ; Chaperonin 60 ; Cholesterol ; Computational Biology ; Computer Simulation* ; Epitopes ; Humans ; Immune System* ; Immunity, Cellular ; Lipoproteins ; Lipoproteins, LDL ; T-Lymphocytes ; Vaccines

This study is to explore the interventional effects of fluvastatin on anti-beta2GPI/beta2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-beta2GPI/beta2GPI, then the TF expression on THP-1 cells was detected by real-time quantitative PCR (RT-qPCR) or TF activity was detected by kit. TNF-alpha mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-kappaB p65 and inhibitory protein of NF-kappaB (IkappaB-alpha) were measured by Western blotting. The results suggested that the expression of TF and TNF-alpha on THP-1 cells was significantly up-regulated with treatment of anti-beta2GPI/beta2GPI complex (100 mg x L(-1)), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mg x L(-1)) could decrease TF (mRNA and activity) expression and the level of TNF-alpha (mRNA and protein) in THP-1 cells with anti-beta2GPI/beta2GPI complex. The expression of TF and TNF-alpha was shown in a concentration-dependent manner. Moreover, anti-beta2GPI/beta2GPI complex could downregulate IkappaB-alpha levels and increase the levels of phospho-NF-kappaB p65. And these effects of anti-beta2GPI/beta2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-kappaB signal transduction pathway, thereby inhibit the effects of anti-beta2GPI/beta2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-alpha.
Antigen-Antibody Complex ; pharmacology ; Cell Line ; Dose-Response Relationship, Drug ; Fatty Acids, Monounsaturated ; administration & dosage ; pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; administration & dosage ; pharmacology ; I-kappa B Proteins ; metabolism ; Indoles ; administration & dosage ; pharmacology ; Monocytes ; cytology ; metabolism ; NF-KappaB Inhibitor alpha ; Phosphorylation ; RNA, Messenger ; metabolism ; Signal Transduction ; drug effects ; Thromboplastin ; genetics ; metabolism ; Transcription Factor RelA ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; beta 2-Glycoprotein I ; antagonists & inhibitors ; immunology

Antibodies to cardiolipin and other phospholipid have been associated with recurrent thrombotic events, including ischemic strokes, especially in children and young adults. Recently it has been shown that anti-beta2-glycoprotein I antibodies may be more specific in predicting thrombosis. We report a case of anterior spinal artery syndrome with elevated titer of antibodies to beta2-glycoprotein I in young adult.
Anterior Spinal Artery Syndrome ; Antibodies ; Antiphospholipid Syndrome ; beta 2-Glycoprotein I ; Cardiolipins ; Child ; Humans ; Stroke ; Thrombosis ; Young Adult

OBJECTIVETo study the value of apolipoprotein H (apoH) gene expression in peripheral blood mononuclear cell (PBMC) and urinary N-Acetyl-beta-D-Glucosaminidase (NAG) and retinal-binding protein (RBP) in the early diagnosis of renal function damage in neonates.

METHODSSixty sick neonates who renal function damage probably occurred were enrolled. The blood and urinary samples were collected twice within 48 hrs following admission, with an interval of 12-24 hrs. Expression of apoH gene in PBMC was determined with RT-PCR. The levels of blood urea nitrogen (BUN) and creatinine, and urinary activities of NAG and RBP were measured with enzymatic reaction.

RESULTSThe abnormal rates of blood apoH and urinary NAG and RBP were 73.3%, 83.3% and 76.7%, respectively in the first detection. The second detection for blood apoH and urinary NAG and RBP showed abnormal rates of 70.0%, 66.7% and 76.7%, respectively. There were no significant differences in the abnormal rates between the three markers either in the first or the second detection (P>0.05). Beside there were no significant significances in the abnormal rates between urinary NAG and blood BUN in the second detection, the abnormal rates of blood apoH and urinary NAG and RBP in both detections were significantly higher than those of BUN or creatinine (P<0.01 or 0.05).

CONCLUSIONSThere are identical values of blood apoH gene expression and urinary NAG and RBP in the early diagnosis of renal function damage in neonates. The above three markers are more sensitive to early renal function damage than blood BUN and creatinine.

Acetylglucosaminidase ; urine ; Blood Urea Nitrogen ; Creatinine ; blood ; Female ; Humans ; Infant, Newborn ; Kidney Diseases ; diagnosis ; physiopathology ; Male ; Retinol-Binding Proteins ; urine ; beta 2-Glycoprotein I ; blood ; genetics

Thrombosis is a well known manifestation in patients with systemic lupus erythematosus, along with lupus anticoagulant, anticardiolipin antibody and anti beta2-glycoprotein I. We describe here a 44-year-old female with an abdominal aorta thrombosis of SLE and the patient had no antiphospholipid antibodies. She had this unusual site of thrombosis and this was associated with protein C and S deficiency. She had no other cause of thrombosis. After anticoagulant treatment, her thrombosis of the abdominal aorta resolved.
Adult ; Antibodies, Anticardiolipin ; Antibodies, Antiphospholipid ; Aorta ; Aorta, Abdominal ; beta 2-Glycoprotein I ; Female ; Humans ; Lupus Coagulation Inhibitor ; Lupus Erythematosus, Systemic ; Protein C ; Thrombosis

BACKGROUND: The presence of lupus anticoagulants (LA) is a strong risk factor for thrombosis in antiphospholipid syndrome. We investigated the usefulness of addition of silica clotting time (SCT) to the pre-existing dilute Russell's viper venom test (dRVVT) for detection of LA. Also, we analyzed differences in the thrombotic features and the characteristics of antiphospholipid antibodies between dRVVT and SCT. METHODS: A total of 167 patients positive for LA or anti-cardiolipin (anti-CL) antibody and 76 healthy controls were enrolled. The dRVVT and SCT were used for detection of LA. Anti-CL, anti-beta2-glycoprotein I (anti-beta2 GPI) and anti-prothrombin (anti-PT) antibodies were measured using commercial ELISA kits. RESULTS: In detection of thrombosis, the sensitivity of the combined test of SCT and dRVVT was 56.4%, which was higher than that of dRVVT alone (46.2%) or SCT alone (23.1%). The specificity of the combined test (80.9%) was comparable to that of dRVVT (81.9%). Also, odds ratio for predicting thrombosis was higher in the combined test than in dRVVT or SCT alone. When normalized LA ratio of the two tests was compared, the group of patients with higher ratio of SCT showed significantly higher prevalence of recurrent abortion and higher positivity of IgG types of anti-CL, anti-beta2 GPI and anti-PT than the group with higher ratio of dRVVT. CONCLUSIONS: Addition of SCT to dRVVT can improve the detection sensitivity of thrombosis in LA test. And the high normalized LA ratio of SCT may be a useful parameter for detection of recurrent abortion.
Adult ; Aged ; Antibodies, Anticardiolipin/analysis ; Antibodies, Antiphospholipid/analysis ; Blood Coagulation Tests/*methods ; Female ; Humans ; Immunoglobulin G/analysis ; Immunoglobulin M/analysis ; Lupus Coagulation Inhibitor/*blood ; Male ; Middle Aged ; Prothrombin/immunology ; Prothrombin Time/methods ; Reagent Kits, Diagnostic ; Sensitivity and Specificity ; Silicon Dioxide/*chemistry ; Thrombosis/diagnosis ; beta 2-Glycoprotein I/immunology

OBJECTIVETo further study the binding character of hepatitis B surface antigen (HBsAg) and beta 2-glycoprotein I (beta2GP I) and to explore whether beta2GP I plays an important role in the hepatotropism of hepatitis B virus.

METHODSUsing Western blot technique, we observed the binding character of the HBsAg with reduced and non-reduced beta2GP I.

RESULTSrHBsAgs with reduced and non-reduced beta2GP I showed identical binding activity.

CONCLUSIONSThe binding activity of HBsAg is dependent on tandem residues, but not on conformational structures of beta2GP I. There is a specific binding between HBV and beta2GP I, which may play an important role in HBV infection and is one of the reasons of hepatotropism of HBV.

Hepatitis B ; virology ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B virus ; pathogenicity ; Humans ; Viral Envelope Proteins ; blood ; beta 2-Glycoprotein I ; blood