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Biomedical subjects

K Gohchi

Publications and source records attributed to K Gohchi.

At least 19 recordsLinked to original sources

Two antiprothrombin antibodies against prothrombin and prothrombin-phosphatidyl serine show partial but not total identity.

Recently, an enzyme-linked immunosorbent assay (ELISA) using prothrombin (PT) as the antigen has become a widely used test. Two ELISA methods for the detection of antiprothrombin antibody have been used extensively: one method employs PT as an antigen (aPT), and the other employs PT and phosphatidyl serine (aPT/PS) as antigens along with Ca. However, the results obtained by the two methods are not necessarily consistent with each other even using the same samples, suggesting the possibility that aPT and aPT/PS are different antibodies. We conducted an investigation to determine whether aPT and aPT/PS are identical or different antibodies. Five patients who were positive for both tests become negative to aPT after absorption with an aPT-ELISA plate or fluid-phase PT; however, they retained reactivity to aPT/PS after the same absorption procedure. These results suggest that aPT and aPT/PS are partially identical, yet still different antibodies. However, further examination employing more samples may be needed to verify our hypothesis including clarification of the clinicopathological significance of these antibodies in the future.

Adult↗

Increased factor VIIa levels in systemic lupus erythematosus patients with lupus anticoagulant.

Recurrent fetal loss, and/or arterio-venous thrombosis are frequent complications in patients with the antiphospholipid antibodies (aPL), anticardiolipin antibody (aCL) and/or lupus anticoagulant (LA). Furthermore, patients with LA have been found to be more susceptible to thrombosis than those with aCL, thus suggesting differences in the pathogenesis of aCL and LA. We examined the systemic lupus erythematosus (SLE) patients with aCL and/or LA for differences in the markers for hypercoagulable state, including thrombin-antithrombin complex (TAT), prothrombin fragment 1 + 2 (F1 + 2), thrombomodulin (TM) and activated factor VII (FVIIa), and lipoprotein (a) (Lp(a)), which is a well-known risk factor for thrombosis. The FVIIa concentration was significantly higher in the LA-positive patients than in the aCL-positive and aPL-negative patients. No significant differences in TAT, F1 + 2, TM, and Lp(a) values were found among the aCL-positive, LA-positive and LA-negative patients groups. These findings indicate that patients with LA were in a more prethrombotic state than those with aCL. The measurement of FVIIa may serve as a useful predictive marker for thrombosis, but further studies are needed to clarify the mechanisms of thrombosis in this clinical setting.

Adult↗

Anti-endothelial cell antibodies to the endothelial hybridoma cell line (EAhy926) in systemic lupus erythematosus patients with antiphospholipid antibodies.

The endothelial hybridoma (EAhy926) cell line was employed to clarify whether antiphospholipid antibodies (aPA) [lupus anticoagulant (LA), antiprothrombin antibody (aPT) and/or anticardiolipin antibody (aCL)] and anti-endothelial cell antibodies (AECA) are identical, and establish whether beta2-glycoprotein I (beta2-GPI) is needed for reactivity of aPA to endothelial cells. Ig-G AECA was positive in 9/30 SLE patients with aPA (30.0%) and 10/22 SLE patients negative for aPA (45.5%). Ig-M AECA was positive in one SLE patient with aPA and one SLE patient without aPA. AECA-positivity was not significantly different among unfixed, TNF-stimulated and fixed EAhy926. The influence of beta2-GPI on the reactivity of serum to EAhy926 was minimal, and absorption experiments of serum with cardiolipin-liposome/beta2-GPI or phosphatidylserine-liposome/prothrombin gave little evidence of cross-reactivity of aPA and AECA. The results of our study suggest that aPA and AECA may have partially cross-reacted, but were different antibodies. However, further study is needed to clarify the clinico-pathological significance of AECA.

Antibodies↗

Negligible synergistic effect of beta2-glycoprotein I on the reactivity of antioxidized low-density lipoprotein antibody to oxidized low-density lipoprotein.

We conducted this study to investigate whether antioxidized low-density lipoprotein (a-oxLDL) is an antibody to cryptic and/or neo-antigen on beta2-glycoprotein I (GPI), which is introduced by binding to anionic phospholipid, similar to that of GPI-dependent anticardiolipin antibody (aCL) employing a-oxLDL ELISA. We found that no significant optical density differences existed among systemic lupus erythematosus patients, including cases with aCL and/or lupus anticoagulant positivity, before and after the addition of GPI. Our results suggest that a-oxLDL is not an antibody to denatured GPI, but rather to oxLDL.

Autoantibodies↗

Buffer may be the critical factor in measurement of anti-prothrombin antibody on a gamma-ray-irradiated plate by enzyme-linked immunosorbent assay.

We investigated the influence of different buffers (Tris-buffer and phosphate buffered saline (PBS)/Tween-20 buffer) on anti-prothrombin antibody (aPT) measurement by enzyme-linked immunosorbent assay (ELISA), employing a gamma-ray-irradiated plate. We found considerable discrepancies in aPT positivity between each buffer, and we suggest that the use of Tris-buffer is not suitable for aPT measurement with a gamma-ray-irradiated plate to measure aPT.

Autoantibodies↗

Phosphatidyl serine-dependent antiprothrombin antibody is exclusive to patients with lupus anticoagulant.

We conducted this study to determine whether antiprothrombin antibody (aPT) [to prothrombin (PT) alone or PT/phosphatidyl serine (PS) complex] actually existed in patients with lupus anticoagulant (LA) and/or anticardiolipin antibody (aCL). aPT to PT alone was positive in 2/7 LA-positive (29%) and 3/7 LA/aCL-positive (43%) patients. aPT to PT/PS complex was positive in 4/7 LA-positive (57%) and 4/7 LA/aCL-positive (57%) patients in the presence of Ca2+. However, none of the aCL-positive patients without LA or the LA/aCL-negative patients were positive for aPT and aPT/PS. Thus, we confirmed the existence of aPT and aPT/PS specifically among LA-positive patients. However, the clinicopathological significance of aPT and aPT/PS in this clinical setting is yet to be clarified.

Antibodies, Anticardiolipin↗

Inhibitory activity of anti-beta 2-glycoprotein I antibody on factor Va degradation by activated-protein C and its cofactor protein S.

We investigated the influence of anti-beta 2-glycoprotein I (aGPI), which recently has come to be regarded as anti-cardiolipin antibody (aCL) itself, on factor Va (FVa) degradation by activated protein C/protein S system. We found that aGPI had an inhibitory effect on FVa degradation with beta 2-glycoprotein I-dependency, thus suggesting aGPI/aCL is a highly possible factor as the pathogenesis of thrombosis observed in aGPI/aCL-positive patients.

Animals↗

Resistance to activated protein C activity of an anti-beta 2-glycoprotein I antibody in the presence of beta 2-glycoprotein I.

Some researchers claim that lupus anticoagulant-positive plasma may cause a false-positive reaction in the test for activated protein C (APC) resistance, a hereditary thrombophilic state characterized by abnormal factor V, which frequently causes venous thrombosis. We investigated whether anti-beta 2-glycoprotein I antibody (aGPI), which has recently come to be regarded as an anti-cardiolipin antibody (aCL) itself, might have an effect on the APC resistance test.

Antibodies, Anticardiolipin↗

Prevalence of beta 2-glycoprotein I antibody in systemic lupus erythematosus patients with beta 2-glycoprotein I dependent antiphospholipid antibodies.

OBJECTIVE: To investigate whether beta 2-glycoprotein I antibody (aGPI) exists in sera that are positive for antiphospholipid antibodies (aPL). METHODS: Thirty six patients with systemic lupus erythematosus (SLE) and 20 healthy volunteers were recruited. GPI independent and dependent aPL (anticardiolipin (aCL), antiphosphatidylserine, antiphosphatidylinositol, antiphosphatidic acid) were measured using a conventional enzyme linked immunosorbent assay (ELISA). aGPI was measured by an ELISA using a gamma irradiated plate coated with purified GPI. RESULTS: Twenty of 36 SLE patients were positive for at least one of the GPI-dependent aPL. Five of these 20 were also positive for aGPI. Another five of the 20 showed low GPI dependency aCL antibodies; however, three of these patients required GPI for binding to phosphatidylserine, phosphatidylinositol, or both. CONCLUSION: We confirmed the existence of aGPI in patients with true GPI dependent aPL. From these results, we recommend the use of a gamma irradiated plate with GPI as antigen for the detection of true GPI dependent aPL or aGPI.

Antibodies, Anticardiolipin↗

High prevalence of anti-phospholipid antibodies and anti-thyroglobulin antibody in patients with hepatitis C virus infection treated with interferon-alpha.

OBJECTIVES AND METHODS: We investigated the prevalence rate of beta 2-glycoprotein I (beta 2-GPI)-dependent antiphospholipid antibodies (aPL)[anti-cardiolipin antibody (aCL), anti-phosphadidylserine antibody (aPS), and anti-phosphatidic acid antibody (aPA)], antinuclear antibody (ANA), anti-deoxyribonucleic acid antibody (aDNA), anti-thyroglobulin antibody (aTG), and anti-thyroid peroxidase antibody (aTPO) in 56 patients with hepatitis C virus (HCV) infection and correlated the results with inteferon-alpha (IFN) treatment. RESULTS: aCL, aPS, and aPA were positive in, respectively, 7/56 (13%), 12/56 (21%), and 13/56 (23%) patients before treatment. aPS and aPA appeared in 6/44 and 9/43 and disappeared in 6/12 and 2/13 patients, respectively, after IFN treatment; the differences were statistically significant. The changes in OD readings were higher in the group of patients who became positive for aPS and aPA than in those who became negative after treatment. The positive rates of aTG and aTPO in the patient group were statistically higher than in the healthy controls, and aTG developed in four patients and disappeared in two. No obvious changes in aTPO were observed; however, the aTPO titer was increased in four previously positive patients. None of the patients positive for any antibodies developed an abnormality associated with these antibodies during an observation period of up to 1 yr. CONCLUSIONS: The pathogenesis of production and clinical significance of aPL, ATG/aTPO in this clinical setting are unclear, but immunological disturbances, such as the effects of HCV infection and/or IFN treatment, were considered to be a possibility. Further investigation is needed to clarify whether HCV/aPL- and/or aTG/aTPO-positive patients treated with IFN might develop aPL-associated complications and/or autoimmune disease(es), in the future and to confirm whether IFN treatment justifies the outcome in this clinical setting.

Adult↗