Obsessive-compulsive disorder and central nervous system autoimmunity.
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Antibodies↗
Biomedical subjects
J A McIntyre
Publications and source records attributed to J A McIntyre.
Antiphospholipid and glutamic acid decarboxylase antibodies in patients with focal epilepsy.
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Adolescent↗
Testing for antiphospholipid antibody (aPL) specificities in retrospective "normal" cerebral spinal fluid (CSF).
Antiphospholipid antibodies (aPL) have been found in the blood of patients with systemic and neurological disease. The rare reports of aPL in cerebral spinal fluid (CSF) have been limited mostly to IgG and IgM anticardiolipin (aCL). Our published finding of IgA aPE in the CSF of a young stroke victim prompted us to establish "normal" CSF aPL values for a panel of aPL, which included aCL, antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE) and antiphosphatidylcholine (aPC). CSF samples were tested by ELISA for IgG, IgM and IgA aPL. In addition, the CSF samples were tested for activity in the presence and absence of phospholipid (PL) binding plasma-proteins. A total of 24 data points were obtained for each CSF sample. We tested 59 CSF samples obtained from 59 patients who were undergoing evaluation for systemic or neurologic diseases. All CSF samples had normal protein, glucose and cell counts. Ten of the 59 CSF samples (17%) had elevated aPL optical density (OD) values an order of magnitude higher than the other 49 CSF samples for one or more aPL specificity and/or isotype. One CSF sample had both PL-binding protein dependent and independent IgG aPE activity. Another CSF sample showed both IgG aPE and aPC reactivity. The remaining eight CSF samples showed single aPL findings; IgG aPE (5), IgG aPC (1), IgG aCL (1) and IgM aPC (1). Seven of 10 patients with elevated CSF values were females. As expected, most "normal" aPL OD values were substantially lower in CSF than those we have reported in blood samples from volunteer blood donors.
Adolescent↗
Anti-annexin A5 antibodies in reproductive failures in relation to antiphospholipid antibodies and phosphatidylserine.
PROBLEM: The presence of IgG anti-annexin A5 (IgGalphaA5) and/or antiphospholipid antibodies (aPL) are risk factors associated with recurrent spontaneous abortion. Problems are whether IgA antiannexin A5 (IgAalphaA5) is pathogenic, and how IgGalphaA5 works. METHOD OF STUDY: Blood samples from 238 patients with early recurrent spontaneous abortion, 48 patients with recurrent in vitro fertilization-embryo transfer failure, 179 non-pregnant women and 120 pregnant controls were tested for IgAalphaA5 by enzyme-linked immunosorbent assay. We also determined if IgGalphaA5 appeared coincident with aPL. The antigenic epitope(s) recognized by IgGalphaA5 was investigated. RESULTS: We observed no difference between patients and controls for IgAalphaA5. The prevalence of IgGalphaA5 was not different statistically between patient samples with or without aPL. Patient IgGalphaA5 bound annexin A5 when the latter was free/unbound but not when annexin A5 was associated with phospholipid. CONCLUSIONS: The IgAalphaA5 does not appear to be pathogenic. IgGalphaA5 works to make a complex with annexin A5 without relation to aPLs, which may reduce annexin A5 available for binding to trophoblast.
Abortion, Spontaneous↗
Antiphospholipid antibodies in implantation failures.
PROBLEM: The amino phospholipids (PL), phosphatidylserine (PS) and phosphatidylethanolamine (PE) are distributed asymmetrically in the plasma membranes of eucaryotic cells. This arrangement involves active transport of PS and PE from the outer to inner membrane leaflet by an aminophospholipid translocase (flipase). Cell activation, injury and programmed cell death (apoptosis) cause collapse of the PS/PE asymmetry by activation of another enzyme system, scramblase. Unlike other cells, the developing trophoblast exteriorizes PS during its differentiation. METHODS OF STUDY: An analysis of published and unpublished data. RESULTS: The trophoblast is targeted by antiphospholipid antibodies (aPL), especially to PS (aPS). Cardiolipin is not present in the trophoblast plasma membrane, nonetheless, anticardiolipin (aCL) has been implicated in trophoblast pathology. The aPS and aCL are often crossreactive. Both animal and in vitro experimental models have shown monoclonal and polyclonal aPS and aCL to specifically destroy trophoblast, inhibit syncytium formation, halt human chorionic gonadatropin (hCG) production, and limit trophoblast invasion. Antibodies to PE (aPE) have not been well characterized, however, recent reports from several independent laboratories document that aPE are associated significantly with very early (embryonic) recurrent pregnancy loss (RPL). Umeda and coworkers have shown that during cytokinesis (late telophase) of Chinese hamster ovary (CHO) cells, formation of PE rafts in cleavage furrows is required for completion of cell division and formation of daughter cells. This raises the question whether aPE might interfere with implantation and cell division during embryogenesis. CONCLUSIONS: A role for aPL in implantation failure and occult pregnancy loss constitutes the basis of this overview.
Animals↗
Venous thromboembolism in the antiphospholipid syndrome: management guidelines for secondary prophylaxis.
Venous thromboembolism (VTE) in patients suffering from the antiphospholipid syndrome (APS) has been reported in almost any location of the vessel tree and the risk of recurrences has been found in several studies to be more closely associated with the presence of lupus anticoagulant than with the positivity for anti-cardiolipin antibodies. The thrombophilic state of APS raises the problem of the secondary prophylaxis to avoid VTE recurrences. For APS patients with VTE, published data appear to support a longer warfarin treatment if compared with the standard management of antiphospholipid (aPL)-negative patients with VTE. The question of how long oral anticoagulant treatment should be continued for APS patients, however, remains unanswered. Concerning the intensity of anticoagulation, several authors recommend a target international normalized ratio (INR) between 3.0 and 4.0 to efficiently protect from VTE recurrences. A recent decision analysis study does support such a suggestion. On the contrary, in a few prospective studies regimens with lower target INRs appear to be effective, and some authors therefore recommend a target INR of between 2.0 and 3.0. Specific large and prospective trials are needed to address this question. Until such information becomes available, individualized treatment according to the patient's individual risk factors for both bleeding and thrombosis is the general practice.
Administration, Oral↗
Antiphospholipid antibodies and renal transplantation: a risk assessment.
Data from 110 transplanted patients show that the presence of antiphospholipid antibodies (aPL) at the time of transplantation is an important risk factor for early renal allograft failure. Sera were tested for IgG, IgM and IgA to CL, PS, PE and PC. Haemodialysis patients had a significantly higher incidence of aPL compared to patients who did not receive haemodialysis (P = 0.0171). aPL-positive ESRD patients on peritoneal dialysis (CAPD) or who had never received haemodialysis were at maximal risk; 100% failure (P = 0.0022). aPL-positive patients receiving haemodialysis were not at such risk. Biopsy findings from the failed kidneys show abundant fibrin deposition in the microvasculature. Serial blood samples from transplanted patients showed aPL titres to decrease immediately after transplant and increase after removal of the failed graft, indicating that aPL specifically target the allografts. To confirm this, we were able to isolate aPL from a failed graft after transplant nephrectomy. Ninety-seven per cent of the aPL-positive patients' historic pre-transplant serum samples demonstrated the presence of the same aPL specificity detected in the final crossmatch sera. The exposure to heparin during haemodialysis suggested to us that heparin reduces the risk of clotting in aPL positive transplant candidates. To lessen the risk of graft loss in aPL positive kidney transplant patients (including CAPD), subcutaneous heparin was administered peri- and post-operatively. To date, none of the heparin-treated aPL-positive transplanted patients suffered an early graft loss. Further, they experienced fewer rejection episodes requiring biopsy and thus are prescribed less steroid therapy than patients not treated with heparin.
Antibodies, Antiphospholipid↗
Certain autoantibodies to phosphatidylethanolamine (aPE) recognize factor XI and prekallikrein independently or in addition to the kininogens.
Recent evidence shows that many antiphospholipid antibodies (aPL) to negatively-charged phospholipid (PL) do not target anionic PL per se, but are specific for anionic PL-binding plasma proteins, for example, beta(2)-glycoprotein I (beta(2)-GPI) and prothrombin. We also reported that certain antiphosphatidylethanolamine antibodies (aPE) are not specific for phosphatidylethanolamine (PE) per se, but are directed to PE-binding plasma proteins, high molecular weight kininogen (HK), and low molecular weight kininogen (LK). Additional studies have shown that certain aPE failed to recognize purified kininogens but continued to produce aPE ELISA reactivity in the presence of semipurified HK preparations containing the HK binding proteins, factor XI (FXI) and prekallikrein (PK). We therefore investigated if certain of these aPE recognized FXI and/or PK. In this study we observed that aPE can recognize contact proteins FXI and PK independently or in combination with HK. Since contact proteins such as HK, PK and factor XII (FXII) have anti-coagulant and profibrinolytic functions, the pathophysiological role of aPE has yet to be elucidated. We propose that aPE of different specificities may initiate or promote characteristics pathological conditions in patients with thrombosis or recurrent pregnancy losses.
Animals↗
Structural integrity of the female condom after multiple uses, washing, drying, and re-lubrication.
Establishing the safety of re-using the female condom could significantly increase women's access to barrier methods especially in poorer countries. In this study, the structural integrity of female condoms was tested (n = 295) after multiple acts of vaginal intercourse. Fifty women were recruited to the study. Each woman re-used one condom up to eight times and washed, dried, and re-lubricated between each use. Structural integrity was measured using standard quality control testing; water-leakage, air-burst, and seam tensile strength. All results were compared to the United States Food and Drug Administration (US FDA) standards for an unused female condom. The results of the structural integrity tests for all cycles were above the FDA minimum standards for seam strength and burst tests. There was no deterioration detected in condoms used 8 times when compared to new female condoms in these tests. Five holes were detected by the water leakage test across all cycles, of which three were detected by the subjects themselves and reported to the investigators, therefore, giving a breakage rate of 1.7%. The holes were not associated with increased number of uses. This study provides further evidence that suggests the structural integrity of the female condom after multiple use is still within FDA minimum standards, although random holes resulting from handling occur infrequently with the re-use procedure.
Coitus↗
Decreased suppression of antibody-dependent cellular cytotoxicity by seminal plasma in unexplained infertility.
OBJECTIVE: To determine whether seminal plasma (SP) from unexplained infertile males has different suppressive activity on antibody-dependent cellular cytotoxicity (ADCC) than SP from fertile males or SP from males of couples with known infertility factor. DESIGN: Comparative clinical/experimental study. SETTING: In vitro fertilization program in a university hospital and a hospital research laboratory. PATIENT(S): A total of 245 SP samples from 174 infertile and 16 fertile couples were compared. INTERVENTION(S): SP suppression of ADCC was measured by using human 51chromium-labeled red blood cells (RBC), sensitized with IgG-rabbit-anti-human-RBC as targets and peripheral blood lymphocytes as effector cells. MAIN OUTCOME MEASURE(S): Suppressive activity of each sample was determined by calculating 51Cr-release in the presence and absence of SP. RESULT(S): When analyzed with respect to sperm number, motility, and morphology, suppressive activities of samples with normal semen analyses (n = 142) were significantly higher (x = 37% +/- 14%) than suppressive activities of abnormal samples (n = 103; x = 32% +/- 13%). There was no strong correlation of suppressive activity to other semen parameters. Within the andrologically normal males, SP from the unexplained infertile couples (n = 15) showed significantly lower suppressive activity (x = 24% +/- 11%) compared with the SP from fertile males (n = 16; x = 35% +/- 13%) and from couples with female infertility factor (n = 65; x = 39% +/- 14%). CONCLUSION(S): Loss of suppressive activity is associated with unexplained infertility, even in male patients who previously were considered normal by traditional methods of semen analysis.
Antibody-Dependent Cell Cytotoxicity↗
Anti-annexin V antibodies in patients with early pregnancy loss or implantation failures.
OBJECTIVE: To describe the prevalence of annexin V antibodies (aANX) in women with early recurrent pregnancy losses (RPLs) or recurrent IVF-ET failure. DESIGN: Retrospective data analysis. SETTING: Tokai University Hospital, Kanagawa, Japan. PATIENT(S): Two hundred thirty-eight patients with RPLs, 48 patients with recurrent IVF-ET failure and 179 nonpregnant and 120 pregnant control group women. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): ELISA was used to measure autoantibodies to annexin V. RESULT(S): An ELISA system developed for aANX revealed a dose-dependent relationship between annexin V and aANX. The positive/negative cutoff was set at 7 multiples of the median based on the 99th percentile of normal nonpregnant control group patients. Patients with RPLs (5.5%) or recurrent IVF-ET failure (8.3%) had a significantly increased incidence of aANX (IgG) compared with normal nonpregnant (1.1%) or pregnant control group women (0), whereas the prevalence of aANX between both patient groups or between both control groups was not statistically different. Specificity was confirmed by absorption studies using annexin V and by immunoblots. CONCLUSION(S): Our data show that aANX are associated with both RPLs and IVF-ET failure. We propose that anti-annexin V antibodies should be considered a risk factor for these reproductive failures.
Abortion, Habitual↗
Clearance of antiphospholipid antibodies in pregnancies treated with heparin.
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Abortion, Habitual↗
Antiphospholipid antibodies. Risk assessments for solid organ, bone marrow, and tissue transplantation.
The literature pertaining to transplantation of solid organs, bone marrow, and other tissues in aPL-positive patients has been reviewed. The effects that aPL have relative to BMT are altogether different than those ascribed to solid organs and tissues. By definition, the transplantation of allogeneic bone marrow serves to reconstitute the recipient with a completely new and genetically different repertoire of antibody-producing cells. Previously aPL-positive bone marrow recipients become aPL-negative subsequent to transplantation assuming that the marrow donor is aPL-negative. These observations are the basis for contemporary experimental approaches to curing certain autoimmune diseases with BMT. Similarly, it would follow that an aPL-negative patient provided cells from an aPL-positive donor could become aPL-positive and suffer increased risk for thrombosis. From the data provided in most of the non-bone marrow publications, the presence of aPL should be considered a grave risk factor for any potential solid organ or tissue transplant candidate. Peritoneal dialysis patients seem to be at maximal risk. Given the serious emotional and economic impact of irreversible thrombotic loss suffered by organ transplant recipients, these factors alone should justify the modest expense of pretransplant aPL screening. In the United States, the average cost of losing a kidney transplant to aPL-associated thrombosis was estimated from 1996 data to be $82,000. The cost of losing a heart or liver is measured not only in dollars but often in the patient's life. The encouraging news, however, is that once aPL are identified before transplantation, prophylactic anticoagulation seems to be capable of forestalling untoward aPL-associated allograft events. Clearly, much remains to be discovered in exploring the pathobiologic characteristics of aPL in the laboratory as well as in neutralizing their procoagulant effects at the bedside.
Animals↗
Report of a new DRB1*13 allele: DRB1*1336.
This brief communication describes the characterization of a new allele, DRB1*1336.
Base Sequence↗
Different antiphospholipid antibody specificities are found in association with early repeated pregnancy loss versus recurrent IVF-failure patients.
PROBLEM: Patients having in vitro fertilization and embryo transfer (IVF-ET) failures show an increased incidence of antiphospholipid (aPL) antibodies; but controversy exists whether aPL can induce IVF-failure. This study was designed to compare aPL specificities between recurrent IVF-failure patients versus repeated early pregnancy loss (RPL) patients. METHOD OF STUDY: Anticardiolipin (aCL), lupus anticoagulant (LA), antiphosphatidylserine (aPS), antiphosphatidylethanolamine (aPE), and antinuclear antibodies (ANA) were measured in 74 recurrent IVF-ET failure patients and compared with 273 early RPL patients ( < 10 weeks). RESULTS: An increased incidence of IgG-aPE and ANA was observed for both groups in comparison with controls. Patients with recurrent IVF-ET failure showed a significantly higher prevalence of IgG-aPS (P = 0.02) and IgG-aCL (P = 0.02) when compared with early RPL patients or controls. CONCLUSIONS: IgG-aPS and IgG-aCL may be responsible for some IVF-failures. Additional studies are needed to clarify the pathogenic role of IgG-aPS and IgG-aCL on IVF-ET failure.
Abortion, Habitual↗
Acceptability of the female condom in different groups of women in South Africa--a multicentred study to inform the national female condom introductory strategy.
OBJECTIVES: To assess the acceptability of the female condom to different groups of women and their partners in South Africa. DESIGN: Descriptive, cross-sectional study. SETTING: Multicentre study conducted in five sites. SUBJECTS: The study recruited 678 women from five centres to an acceptability trial of the female condom. Acceptability and successful use varied between the centres. OUTCOME MEASURES: Factors affecting successful use and willingness and intention to use the method again. RESULTS: In total, 209 women used the condom at least once. Discontinuation rates were high, with partner reluctance to try the method as the main reason given for discontinuation at all sites. Women who had previous experience with the male condom or who received a more intensive training session generally found the device easier to use. The main issues concerning women were over-lubrication (27%) and concern that the device was too large (28%). The majority of women said that they would be interested in using the method again (86%) and would recommend it to friends (95%). CONCLUSIONS: Overcoming partner opposition is an important issue to address when introducing the method. The study was used to address the national introductory strategy of the female condom, which began in 1998.
Adolescent↗
Henoch-Schönlein purpura and stroke: antiphosphatidylethanolamine antibody in CSF and serum.
A 15-year-old girl with features of Henoch-Schönlein purpura and brain infarct had a transient IgA antiphosphatidylethanolamine antibody (aPE) in her serum and CSF that disappeared 5 months after presentation. Serum aPE is known to be associated with thrombotic events. The authors found no aPE in the CSF of two control individuals or in the serum of two patients with active Henoch-Schönlein purpura without neurologic involvement. The patient may represent a variant of antiphospholipid antibody syndrome.
Adolescent↗
Advances and research directions in the prevention of mother-to-child HIV-1 transmission.
Although substantial progress has been made in preventing mother-to-child HIV-1 transmission in the past decade, critical research questions remain. Two perinatal epidemics now exist. In more-developed countries, integration of prenatal HIV-1 counselling and testing programmes into an existing antenatal infrastructure, availability of effective antiretroviral prophylaxis, and access to infant formula have resulted in new perinatal infections becoming rare. However, identification of missed prevention opportunities, the causes of prophylaxis failure, and the potential effects of in-utero antiretroviral exposure have become a priority. In less-developed countries, antenatal care is limited, testing programmes are almost non-existent, effective interventions remain unimplemented, and prevention of postnatal transmission through breastmilk while maintaining adequate infant nutrition is a major dilemma. The challenge for the next decade is to simultaneously address questions relevant to both epidemics while bridging the gap in prevention of perinatal transmission between more-developed and less-developed countries.
AIDS Serodiagnosis↗