Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relapsing polychondritis (RP) is an extremely rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM- and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG- and IgM-isotypes) and anti-beta-2-glycoprotein I-antibodies (a beta 2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated a beta 2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP.
Lupus 1998
PMID:Anti-phospholipid-antibodies in patients with relapsing polychondritis. 949 43

A rare SLE patient with central nervous system involvement (CNS-SLE) who relapsed presenting new symptoms associated with the development of serum anti-Sm antibody and was then successfully treated with cyclophosphamide (CY) pulse therapy is presented here. A 47-years old housewife was admitted to Kushiro City General Hospital because of fever, limb erythema and drowsy consciousness in September 1995. On the basis of convulsion, proteinuria, leukopenia, thrombopenia, serum positive tests for both anti-nuclear antibody and anti-SSA antibody and low complement levels, as well as elevations of IgG index and IL-6 in the cerebrospinal fluid (CSF), she was diagnosed as having CNS-SLE. Serum tests for anti CL-beta 2 GPI antibody and lupus anticoaglant was negative. Serum test for HBs antigen was positive. She was treated successfully with methylprednisolone (mPSL) pulse therapy and plasma exchange (PE). Prednisolone was gradually tapered to the dosage of 17.5 mg per day and she was discharged in April 1996. She was re-admitted because of fever, an exacerbation of skin eruption and arthralgia in October 1996. Serum anti-Sm antibody was found to be positive. mPSL pulse therapy was not effective. On the basis of hallucination and elevations of IgG index and IL-6 in the CSF, a diagnosis of relapsed CNS-SLE was made. However the level of IFN-alpha in the CSF was normal. Although PE was not effective, CY pulse therapy was markedly effective.
 ...
PMID:[A recovered case of SLE with central nervous system involvement who relapsed presenting new symptoms associated with development of serum anti-Sm antibody]. 956 77

Antibodies to beta 2-glycoprotein in the serum of patients with antiphospholipid syndrome (APS) were found by many investigators, but their results appeared contraversional. We studied clinical significance of antibodies to beta 2-glycoprotein I (anti-beta 2-GPI) in patients with SLE. 69 patients with verified SLE were examined for lupus anticoagulant (LA), antibodies to cardiolipin (aCL) and anti-beta 2-GPI. 44(65%), 46(67%), 49(71%), 19(28%), 16(23%) patients were positive for LA, IgG-aCL, IgM-aCL, IgG-anti-beta 2-GPI and IgM-anti-beta 2-GPI, respectively. Hyperproduction of IgG-anti-beta 2-GPI correlated with APS development as a whole, its separate clinical symptoms (venous and arterial thromboembolism, obstetric pathology and thrombocytopenia) and some comcomitant clinical signs (trophic crural ulcer, hemolytic anemia, valvular heart disorders). Moreover, an increase in concentration of IgM-anti-beta 2-GPI was associated with habitual abortion. Both isotypes of anti-beta 2-GPI occurred more frequently in the sera positive by LA and aCL. It is interesting that we discovered IgG-anti-beta 2-GPI more often in early than late postthrombolytic period. Thus, anti-2b2-GPI is a new serological marker of APS. Its detection is clinically important for upgrading diagnosis of APS.
 ...
PMID:[Antibodies to beta2-glycoprotein I in systemic lupus erythematosus: new laboratory marker of antiphospholipid syndrome]. 957 46

Antiphospholipid syndrome (APLS), is defined as the presence of antiphospholipid antibodies (APLA) associated with clinical phenomena of arterial or venous thrombosis, recurrent spontaneous abortions and thrombocytopenia. APLA represent the family of antibodies of different specificity. They are mostly directed to various anionic phospholipids (cardiolipin, phosphatidylcholine, phosphatidylserine, phosphatidyl acid and phosphatidyl ethanolamine). The part of APLA is directed towards epitope at the structurally changed beta-2-GPI, the so-called anti beta-2-GPI antibodies and the hypothesis was established that the subgroup of APLA was directed towards complex of beta-2-GPI with the phospholipids and oxidized lipoproteins of high and very low density. This could explain the clinically observed association of mutual onset of thrombosis and atherosclerosis. The most frequent target tissues for APLA are endothelial cells, thrombocytes, monocytes, natural anticoagulant system and placenta. APLA can be detected in a serum with one of the following assays: testing of lupus anticoagulant presence, determination of anticardiolipin antibodies (ACLA) concentration by ELISA and by testing the false positivity of VDRL test (standard test for syphilis). The pathological base for so-called vasculopathy in APLS are arterial and venous thrombosis. Clinical manifestations of APLS are mainly the result of blood vessels' occlusion but the thrombotic mass deposition on the surface of the heart valves may also occur. Clinically APLS can be divided into primary and secondary one, and manifestations of the secondary APLS are mainly expressed in the patients with SLE. Some clinical and serological variants of primary APLS were also described. The tendency for thrombotic process as a crucial characteristic of the syndrome and the lack of inflammation, imposes the choice of antithrombotic and anticoagulant therapy.
 ...
PMID:[The antiphospholipid syndrome--yesterday, today, tomorrow]. 962 52

The relationship between presence of anti-beta2-glycoprotein I autoantibodies (abeta2-GPI) and history of thrombosis is now widely known. However, differences in the methodology of abeta2-GPI detection have made the comparison of data from different laboratories extremely difficult. We discuss the significance of abeta2-GPI of the IgG, IgM and IgA isotypes, and our approach to developing an easier and more reproducible method for the detection of this autoantibody. In addition, we present data that shows that commercially available enzyme immunoassay plates differ regarding detectability of abeta2-GPI. Since the clinical significance of this heterogeneity is presently unclear, the set-up of the detection systems and interpretation of data need great care.
Lupus 1998
PMID:Anti-beta2-glycoprotein I antibodies. 981 83

Beta2-Glycoprotein I (beta2-GPI) is a major antigen for anticardiolipin antibodies (aCL) induced in patients with antiphospholipid syndrome and their antigenic epitopes are cryptic. The epitopes appear on the surface of beta2-GPI molecule only when beta2-GPI interacts with lipid membranes containing negatively charged phospholipids or polyoxygenated polystyrene surface. Our data also indicated that CuSO4-oxidized low density lipoproteins (oxLDL) are subsequently targeted by beta2-GPI and aCL; however, malonedialdehyde (MDA)-modified LDL were recognized neither by beta2-GPI nor aCL. Beta2-GPI binding to LDL was rapidly increased by incubation with CuSO4. Oxidation of lipoproteins was accompanied with the increment of thiobarbituric acid-reactive substances (TBARS) and denature of apolipoprotein. Ligands on LDL for beta2-GPI seemed to be intermediate oxidative derivatives which were extractable into the chloroform phase by Bligh and Dyer's extraction, but not MDA. Further, immune responses against beta2-GPI, as an anti-atherogenic protein, were demonstrated to induce atherogenic effect in in vitro oxLDL uptake by macrophages.
Lupus 1998
PMID:Antiphospholipid antibodies and atherosclerosis. 981 91

The aim of this study was to determine if the measurement of anti-beta2-glycoprotein I antibodies (abeta2-GPI) in serum levels contributes to the better characterization of the clinical situation of patients with antiphospholipid syndrome (APS). For this purpose abeta2-GPI of both isotypes was measured in 42 patients with APS and 32 SLE patients without APS. Clinical records of all patients were thoroughly reviewed. The presence of abeta2-GPI was correlated with the clinical manifestations of APS and compared with the presence of anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) activity. There was a positive correlation between levels of aCL and abeta2-GPI for both IgG and IgM isotypes (rho of Spearman=0.82 and 0. 64 respectively, P=0.0001). Both antibodies presented significantly higher titres in LA positive patients (P<0.05). The specificity for APS was 91% for IgG abeta2-GPI vs 75% for IgG aCL and 87% for IgM abeta2-GPI vs 81% for IgM aCL. 68% of patients with thrombosis of 100% of patients with thrombocytopenia showed positive tests for all three markers (aCL, LA, abeta2-GPI). Simultaneous presence of circulating LA and high titres of both aCL and abeta2-GPI identify a subset of patients with primary APS (PAPS) who have a more severe clinical course of the disease. Although the specificity of abeta2-GPI IgG is higher than that of aCL IgG, when all three tests are performed abeta2-GPI testing provides only additional information to that of aCL and LA. Therefore, we concluded that the abeta2-GPI test should not be considered as a substitute for conventional LA or aCL assays. However, performance of abeta2-GPI seems to be important in PAPS with high aCL titres, to alert the physician about the risk for the worst course of the illness.
Lupus 1999
PMID:Do antibodies to beta2-glycoprotein 1 contribute to the better characterization of the antiphospholipid syndrome? 1048 10

The high affinity of human plasma beta2-glycoprotein I (beta(2)GPI), also known as apolipoprotein-H (ApoH), for negatively charged phospholipids determines its implication in a variety of physiological pathways, including blood coagulation and the immune response. beta(2)GPI is considered to be a cofactor for the binding of serum autoantibodies from antiphospholipid syndrome (APS) and correlated with thrombosis, lupus erythematosus and recurrent fetal loss. We solved the beta(2)GPI structure from a crystal form with 84% solvent and present a model containing all 326 amino acid residues and four glycans. The structure reveals four complement control protein modules and a distinctly folding fifth C-terminal domain arranged like beads on a string to form an elongated J-shaped molecule. Domain V folds into a central beta-spiral of four antiparallel beta-sheets with two small helices and an extended C-terminal loop region. It carries a distinct positive charge and the sequence motif CKNKEKKC close to the hydrophobic loop composed of residues LAFW (313-316), resulting in an excellent counterpart for interactions with negatively charged amphiphilic substances. The beta(2)GPI structure reveals potential autoantibody-binding sites and supports mutagenesis studies where Trp316 and CKNKEKKC have been found to be essential for the phospholipid-binding capacity of beta(2)GPI.
 ...
PMID:Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome. 1056 35

Antiphospholipid syndrome is characterized by the presence of high titers of anti-beta(2)-glycoprotein I (beta(2)GPI) antibodies, lupus anticoagulant associated with thromboembolic phenomena, thrombocytopenia and recurrent fetal loss. Single-chain Fv (scFv) were prepared from four anti-beta(2)GPI mAb, CAM, CAL, CAR and 2C4C2, and one anti-ssDNA. All five scFv showed the same antigen binding properties as the original mAb. Replacement of the pathogenic CAM V(H) domain with the non-pathogenic CAL V(H) or anti-ssDNA V(H) decreased the binding affinity of the scFv to beta(2)GPI and completely abrogated the anticoagulant activity. Exchanging the CAM V(H) with anti-DNA V(H) resulted in a shift from anti-beta(2)GPI to anti-ssDNA binding of the scFv. Replacement of the CAM V(L) with CAL V(L) did not affect the binding and activity. BALB/c mice were immunized with the anti-beta(2)GPI scFv, and the scFv resulting from the substitution of the heavy (H) and light (L) chains. The mice which were immunized with CAM, 2C4C2 and CAR scFv developed clinical manifestations of experimental anti-phospholipid syndrome. Elevated titers of mouse anti-cardiolipin (aCL), anti-beta(2)GPI, associated with lupus anticoagulant activity, thrombocytopenia, prolonged activated partial thromboplastin time and a high percentage of fetal resorptions were detected, in the CAM scFv group and in the scFv composed of CAM V(H) groups. High titers of aCL, anti-beta(2)GPI, anti-ss/dsDNA and anti-histone associated with lupus findings were observed in the sera of the 2C4C2 scFv-immunized mice. Immunization with CAL scFv did not lead to any clinical findings. The current study shows that scFv of pathogenic antibodies are capable of inducing the same clinical manifestations as the whole antibody molecule upon active immunization. Replacement of H/L chains point to the importance of the V(H) domains in the pathogenic potential of anti-beta(2)GPI.
 ...
PMID:Characteristics and pathogenic role of anti-beta2-glycoprotein I single-chain Fv domains: induction of experimental antiphospholipid syndrome. 1059 Feb 57

Antiphospholipid syndrome (APS) is an autoimmune disease that accompanies anti-phospholipid antibodies measured as either anti-cardiolipin antibodies (aCL) or lupus anticoagulant. beta(2)-glycoprotein I (beta(2)GPI) is the most common and apparently the best-characterized antigenic target for aCL. To investigate T-cell responses to beta(2)GPI, we stimulated PBMC of 18 APS or systemic lupus erythematosus (SLE) patients carrying anti-beta(2)GPI and 10 healthy controls, using a peptide library covering the beta(2)GPI sequence. We established seven CD4(+) T cell lines reactive with beta(2)GPI peptide. Three of four epitopes for patient-derived T cell lines were p244-264, whereas one T cell line from a control subject also recognized p244-264. Furthermore, there was no tendency for particular HLA class II molecules to present beta(2)GPI peptides. However, cytokine producing patterns were significantly different between T cell lines from patients and those from healthy individuals (p =.028); patients' T cells tend to exhibit higher IL-4 and lower IFN-gamma responses. These T cell lines did not react to beta(2)GPI purified from human plasma. These results indicate that beta(2)GPI-reactive CD4(+) T cells of APS/SLE patients mainly recognize cryptic p244-264 in the context of various HLA class II molecules, and exhibit Th0-Th2-type responses. Our findings may provide a clue to the pathogenesis of APS.
 ...
PMID:Analysis of T cell responses to the beta 2-glycoprotein I-derived peptide library in patients with anti-beta 2-glycoprotein I antibody-associated autoimmunity. 1071 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>