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PubMed1983

The lipid-containing bacteriophage PR4. Effects of altered lipid composition on the virion.

Phage PR4 was grown on a variety of Escherichia coli mutants defective in fatty acid and phospholipid metabolism. The composition of the phage lipids was modified by changing the composition of the host membrane phospholipids. The compositions of both the polar and the acyl moieties of the phospholipids were altered. The proportion of saturated fatty acids in the phage phospholipids was increased in increments from 44% of the total fatty acids to 55%, 61% and 69% of the total fatty acids using a host mutant with a temperature-sensitive defect in unsaturated fatty acid biosynthesis. The increase in saturated fatty acids led to a pronounced loss of infectivity when the phage were incubated at temperatures between 2 degrees C and 30 degrees C (temperatures below those at which the phage were grown). The greater the level of saturated fatty acids in the phage phospholipids, the higher the temperature below which the phage were inactivated. Our results strongly suggest that the phage membrane undergoes a lipid phase transition, which can disrupt and inactivate the virion. The phospholipid composition of PR4 was also altered by using host mutants defective in phosphatidylethanolamine and/or cardiolipin synthesis. Phage PR4 grown on wild-type host strains contains 56% phosphatidylethanolamine, 37% phosphatidylglycerol, 4.6% cardiolipin and no detectable phosphatidylserine. However, in response to changes in the host, PR4 preparations were obtained with phospholipid compositions varying from 28% to 60% in phosphatidylethanolamine, from 22% to 39% in phosphatidylglycerol, from 1% to 15% in cardiolipin and containing as much as 35% phosphatidylserine. These changes in phospholipid composition did not affect the infectivity of the phage. Moreover, the increased level of phosphatidylglycerol in the phage relative to the host was not altered by these manipulations. It is concluded that the net charge of the phage membrane phospholipids is not involved in the selection or function of the viral phospholipids. We also present evidence suggesting that the phage and host membranes do not fuse during the course of infection.

Cold Temperature↗
PubMed2003

Effects of unfractionated and low molecular weight heparin on antiphospholipid antibody binding in vitro.

OBJECTIVE: To compare the efficacy of unfractionated heparin and low molecular weight heparin in the in vitro binding of antiphospholipid antibodies obtained from the sera of patients with recurrent pregnancy loss. METHODS: Women with immunoglobulin (Ig) G antibodies to the phospholipids cardiolipin and phosphatidylserine were selected based on a positive test by a standard enzyme-linked immunosorbent assay (ELISA). The sera were reassayed for antiphospholipid antibodies in a modified ELISA using increasing doses of unfractionated heparin or low molecular weight heparin (0, 16, 32, 64, 128, and 256 IU). Sera were fractionated by unfractionated and low molecular weight heparin affinity chromatography to compare the binding avidity and antiphospholipid antibody activity. RESULTS: All sera demonstrated a dose-dependent inhibition in measured antiphospholipid antibody activity with the addition of unfractionated or low molecular weight heparin. Levels of IgG cardiolipin and IgG phosphatidylserine were significantly inhibited in the presence of 32 IU of low molecular weight heparin (P <.001 and P <.05, respectively) and in the presence of 64 IU of unfractionated heparin (P <.001 and P <.05, respectively). Antiphospholipid antibody binding activity in serum as measured in the ELISA was maximally reduced 76-89% with 256 IU of either heparin derivative. Affinity chromatography with unfractionated or low molecular weight heparin columns absorbed 72% and 66% of IgG cardiolipin activity, respectively, and 46% and 54% of IgG phosphatidylserine activity, respectively. CONCLUSION: These data suggest that low molecular weight heparin and unfractionated heparin reduce the in vitro binding of antiphospholipid antibodies on a per unit basis. Both heparins demonstrate binding activity similar to that of antiphospholipid antibodies in vitro.

Abortion, Habitual↗
PubMed1997

[New targets of antiphospholipid antibodies].

"Antiphospholipid" antibodies (aPL) are a heterogenous group of autoantibodies with clinical importance because of their association with thrombotic events, both venous and arterial. Traditionally, aPL have been assayed using phospholipid-dependent tests and are classified as lupus anticoagulants and anticardiolipin antibodies (ACA), based on the method of detection. Most antibodies associated with the aPL syndrome and detected in standard assays are actually directed against two phospholipid-binding plasma proteins, beta 2 glycoprotein I and prothrombin. These antibodies can also be detected in immunoassays (ELISA) utilizing purified protein antigens, in the absence of phospholipids. The main advantage of beta 2 GPI-ELISA compared with conventional cardiolipin-ELISA appearing from initial clinical studies is greater specificity for the aPL syndrome, due to (i) ignorance of "authentic" ACA that interact directly with cardiolipin; (ii) detection of species specific anti-beta 2 GPI antibodies poorly reactive with bovine beta 2 GPI in the cardiolipin-ELISA. Other proteins proposed as target antigens of aPL are protein C, protein S, annexin V, high- and low-molecular weight kininogens, the latter being involved in the binding of antibodies to phosphatidylethanolamine. The possibility that particular autoantibodies (or combinations of autoantibodies) explain the observed clinical spectrum of the aPL syndrome is attractive, but much remains to be learned about their pathogenicity and origin in order to improve diagnosis and therapy.

Antibodies, Antiphospholipid↗
PubMed2002

DNA-bound lipids of normal and tumor cells: retrospective and outlooks for functional genomics.

By very soft phenol method, the high-molecular-mass natural DNA complexes (10(8)-10(9) Da), which contain 1-3% specific lipids, were isolated from different eukaryotic and prokaryotic cells. Two pools of DNA-bound lipids were isolated: loosely bound (extracted with 35% ethanol) and tightly bound lipids (extracted after additional treatment DNAse I). The composition of these two lipid pools of different sources (rat thymus, liver, regenerating liver, loach sperm, pigeon erythrocytes, Zajdel ascites hepatoma, Ehrlich ascites carcinoma, sarcoma 37, Escherichia coli B, T2 phage) was studied. The DNA-bound lipid pools consist of neutral lipids (NL) and phospholipids (PL), moreover NL is always in a few fold more than PL. The composition of these lipid pools of eukaryotes distinguishes between themselves, mainly, by free cholesterol (minor fraction), cardiolipin (major fraction), and by phosphatidylcholine. Only the tightly bound lipid pool was present in T2 phage DNA. The dramatic redistribution effect between all fractions of NL pools (free and ester cholesterol, free fatty acids, diglycerides) was observed in DNA synthesis phase of cell cycle on the background of the unchanged composition of PL pools. Comparative analysis of DNA-bound lipid pools of normal and cancer cells was carried out. The DNA-bound lipid pools of transformed cells significantly differ from the same normal cells both by PL composition (cardiolipin) and by the presence of additional fractions (mono- and triglycerides) as well. The possible functions of DNA-bound lipid pools, especially of cardiolipin and cholesterol at the attachment of DNA loops to the nuclear matrix, DNA replicon organization, replication, and transcription are discussed.

Animals↗
PubMed1987

Estimation by radiation inactivation of the size of functional units governing Sendai and influenza virus fusion.

The target sizes associated with fusion and hemolysis carried out by Sendai virus envelope glycoproteins were determined by radiation inactivation analysis. The target size for influenza virus mediated fusion with erythrocyte ghosts at pH 5.0 was also determined for comparison; a value of 57 +/- 15 kDa was found, indistinguishable from that reported previously for influenza-mediated fusion of cardiolipin liposomes [Gibson, S., Jung, C. Y., Takahashi, M., & Lenard, J. (1986) Biochemistry 25, 6264-6268]. Sendai-mediated fusion with erythrocyte ghosts at pH 7.0 was likewise inactivated exponentially with increasing radiation dose, yielding a target size of 60 +/- 6 kDa, a value consistent with the molecular weight of a single F-protein molecule. The inactivation curve for Sendai-mediated fusion with cardiolipin liposomes at pH 7.0, however, was more complex. Assuming a "multiple target-single hit" model, the target consisted of 2-3 units of ca. 60 kDa each. A similar target was seen if the liposomes contained 10% gangliosides or if the reaction was measured at pH 5.0, suggesting that fusion occurred by the same mechanism at high and low pH. A target size of 261 +/- 48 kDa was found for Sendai-induced hemolysis, in contrast with influenza, which had a more complex target size for this activity (Gibson et al., 1986). Sendai virus fusion thus occurs by different mechanisms depending upon the nature of the target membrane, since it is mediated by different functional units. Hemolysis is mediated by a functional unit different from that associated with erythrocyte ghost fusion or with cardiolipin liposome fusion.

Animals↗
PubMed1981

Dynamic modulation of mitochondrial inner-membrane lipids in rat heart by dietary fat.

A novel longitudinal feeding design was used to investigate the controlling influence of dietary fatty acids on the dynamic incorporation of fatty-acyl chains into phosphatidylcholine, phosphatidylethanolamine and cardiolipin in inner membrane of cardiac mitochondria. Rats were fed a polyunsaturated-fatty-acid-rich oil (soya-bean oil) for 12 days, crossed-over to a monounsaturated-fatty-acid-rich oil (rapeseed oil) for the next 11 days, then returned to soya-bean oil for 11 more days. Additional rats were fed either soya-bean oil or rapeseed oil only throughout. Rats were killed serially. Regression analysis was used to represent longitudinal flux in membrane lipid fatty-acid composition occurring with change in dietary fat. The fatty-acid composition of phosphatidylcholine, phosphatidylethanolamine and cardiolipin was influenced by dietary oil in a reversible way. Maximal diet influence was achieved in the 11-day cross-over period. Soya-bean oil to rapeseed oil cross-over caused the fatty-acid composition of phosphatidylcholine, phosphatidylethanolamine and cardiolipin to resemble that of rats fed rapeseed oil only. These changes were reversed by crossing back to soya-bean oil, indicating the dynamic state and short half-life of membrane phospholipid fatty-acyl chains. This report demonstrates for the first time in the whole animal fed diets adequate in all nutrients that subcellular membrane lipids rapidly respond to change in dietary fatty-acid balance. The system may be used to assess in vivo the significance of dietary fat in determining membrane physicochemical properties and biochemical functions.

Animals↗
PubMed1984

Cytochrome c mediates electron transfer between ubiquinol-cytochrome c reductase and cytochrome c oxidase by free diffusion along the surface of the membrane.

Ubiquinol oxidase can be reconstituted from ubiquinol-cytochrome c reductase (Complex III) and cytochrome c oxidase (Complex IV) whose endogenous phosphatidylcholine and phosphatidylethanolamine have been replaced by dimyristoylglycerophosphocholine. Phase transition of the lipid has no effect on Complex III and Complex IV activities assayed separately, but ubiquinol oxidase activity rapidly decreases as the temperature is lowered through the phase transition. A spin-labelled yeast cytochrome c derivative has been synthesized. Binding of the cytochrome c to liposomes demonstrates that only cardiolipin is involved under the conditions used for the ubiquinol oxidase experiments. In liposomes consisting of cardiolipin and dimyristoylglycerophosphocholine, e.s.r. (electron-spin-resonance) measurements show that rotational diffusion of cytochrome c is slowed in the gel phase of the latter lipid. We propose that the cytochrome c pool is bound to cardiolipin molecules, whose lateral and rotational diffusion in the bilayer is adequate to account for electron-transport rates.

Cell Membrane↗
PubMed1992

Inhibition of Escherichia coli DNA topoisomerase I activity by phospholipids.

The DNA relaxation activity of Escherichia coli DNA topoisomerase I in vitro was greatly inhibited by cardiolipin. Inhibition also occurred to some extent with phosphatidylglycerol from egg yolk. Analysis with synthetic phospholipid revealed that phosphatidylglycerol containing unsaturated fatty acids exhibited a strong inhibitory effect, whereas inhibition by phosphatidylglycerol containing saturated fatty acids was weak. Phosphatidylethanolamine showed no inhibitory effect. Chlorpromazine, which interacts with phospholipids, suppressed the inhibitory effect of cardiolipin. Cardiolipin and phosphatidylglycerol with unsaturated fatty acid precipitated topoisomerase I even at low concentrations, whereas phosphatidylglycerol from egg yolk and a synthetic phosphatidylglycerol containing saturated fatty acids precipitated this enzyme only at high concentrations. One-third of the total topoisomerase I in E. coli was found in the membrane fraction. Treatment of E. coli cells with chlorpromazine resulted in relaxation of plasmid DNA. This DNA relaxation was not observed in a topA mutant, suggesting that this relaxation by chlorpromazine in vivo is catalysed by topoisomerase I.

Chlorpromazine↗
PubMed2001

Palmitate decreases proton pumping of liver-type cytochrome c oxidase.

The H+/e- stoichiometry of reconstituted cytochrome c oxidase from bovine kidney, containing subunit VIaL (liver type), is 0.5 under standard conditions but 1.0 on addition of 1% cardiolipin to the lipid mixture (asolectin). Low concentrations of palmitate (half-maximal effect at 0.5 microm), but not laurate, myristate, stearate, oleate, 1-hexadecanol, palmitoyl glycerol and palmitoyl CoA, decreased the H+/e- ratio in the presence of cardiolipin from 1.0 to 0.5, accompanied by an increase of coupled, but not of uncoupled respiration of proteoliposomes. Cardiolipin and palmitate did not influence the H+/e- stoichiometry and respiration of reconstituted cytochrome c oxidase from bovine heart, containing subunit VIaH (heart-type). The H+/e- stoichiometry of the heart enzyme, however, is decreased from 1.0 to 0.5 by 5 mm intraliposomal ATP (instead of 5 mm ADP). It is assumed that palmitate binds to subunit VIaL. The partial uncoupling of proton pumping in cytochrome c oxidase is suggested to participate in mammalian thermogenesis.

Animals↗
PubMed1997

Enrichment of antibodies against phospholipids in circulating immune complexes (CIC) in the anti-phospholipid syndrome (APLS).

The aim of this study was to analyse and characterize immunoglobulins in CIC and serum from patients with anti-cardiolipin antibodies. CIC from five patients were isolated by gradient centrifugation and gel filtration. The distribution between serum and CIC of immunoglobulin reactivity against different phospholipids was determined. Serum and CIC contained antibodies against cardiolipin and other negatively charged phospholipids. The relative concentration of these antibodies was higher in the immune complexes than in corresponding sera, and the avidity of antibodies in immune complex form was higher. The presence of high concentrations of antibodies to negatively charged phospholipids in CIC from patients with anti-cardiolipin antibodies could be of pathogenic significance in APLS by conferring characteristics to the complexes of importance for binding to membrane components. This could have special implications with regard to platelet and complement activation, thrombocytopenia and thrombophilia.

Adult↗
PubMed1999

Anti-phospholipid antibodies and CD5+ B cells in HIV infection.

This cross-sectional study evaluates the correlation between anti-phospholipid antibodies and CD5+ B cells in 110 patients infected with HIV-1. There were 89.1% of the patients who had IgG antibodies against cardiolipin and phosphatidylserine. The prevalence of IgM and IgA antibodies was < 22%. AIDS was associated with lower frequencies of IgM antibodies against cardiolipin (P = 0.05) and IgG-antibodies against cardiolipin and phosphatidylserine (P = 0.011). Drug users had higher IgM antibodies against phospholipids than patients from other risk groups (P = 0.02). A history of thromboembolic events was not accompanied by higher levels of anti-phospholipid antibodies (P > 0.2). No correlation between anti-phospholipid antibodies and CD5+ B cells was detected. Percentage part of CD5+ B lymphocytes was elevated in all patients and absolute CD4+ T lymphocyte counts and HIV p24 antigen were inversely correlated. In advanced disease a significant reduction of anti-phospholipid antibodies was contrasted with persistent elevation of CD5+ B lymphocytes. These observations may reflect immunological dysfunction involving apoptosis and endothelial damage rather than polyclonal B cell hyperstimulation. A possible explanation would be that in HIV infection an increased rate of spontaneous apoptosis in peripheral blood lymphocytes is accompanied by functional and structural changes of mitochondria. Therefore, structurally altered mitochondrial phospholipids could serve as antigen to induce specific humoral immune responses.

Adolescent↗
PubMed1999

Anti-idiotype immunomodulation of experimental anti-phospholipid syndrome via effect on Th1/Th2 expression.

Mice with experimental anti-phospholipid syndrome (APS), induced by active immunization with a human anti-cardiolipin MoAb (H-3), were treated with mouse anti-idiotypic MoAb (anti-H3, named S2.9) and with an irrelevant anti-idiotype. The immunized mice produced high titres of mouse anti-cardiolipin antibodies along with clinical manifestations of experimental APS: prolonged activated partial thromboplastin time (aPTT), thrombocytopenia and high rate of fetal loss. Treatment with the specific anti-Id (S2.9) as a whole molecule or F(ab)2 fraction, resulted in a decrease in serum levels of the anti-cardiolipin antibodies, rise in platelet count, shortened aPTT and reduced rate of fetal loss. The anti-Id effect was associated with a rise in the number of IL-2 and interferon-gamma (IFN-gamma)-secreting cells (Th1) and reduction in IL-4- and IL-6-secreting cells (Th2). The beneficial effect of the anti-Id treatment in mice with experimental APS induced by active immunization with an idiotype further supports the idiotypic aetiology of experimental APS and points to the role of Th1 cytokines in suppression of its manifestations.

Abortion, Habitual↗
PubMed2002

Acidic phospholipids inhibit the DNA-binding activity of DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli.

In order to initiate chromosomal DNA replication in Escherichia coli, the DnaA protein must bind to both ATP and the origin of replication (oriC). Acidic phospholipids are known to inhibit DnaA binding to ATP, and here we examine the effects of various phospholipids on DnaA binding to oriC. Among the phospholipids in E. coli membrane, cardiolipin showed the strongest inhibition of DnaA binding to oriC. Synthetic phosphatidylglycerol containing unsaturated fatty acids inhibited binding more potently than did synthetic phosphatidylglycerol containing saturated fatty acids, suggesting that membrane fluidity is important. Thus, acidic phospholipids seem to inhibit DnaA binding to both oriC and adenine nucleotides in the same manner. Adenine nucleotides bound to DnaA did not affect the inhibitory effect of cardiolipin on DnaA binding to oriC. A mobility-shift assay re-vealed that acidic phospholipids inhibited formation of a DnaA-oriC complex containing several DnaA molecules. DNase I footprinting of DnaA binding to oriC showed that two DnaA binding sites (R2 and R3) were more sensitive to cardiolipin than other DnaA binding sites. Based on these in vitro data, the physiological relevance of this inhibitory effect of acidic phospholipids on DnaA binding to oriC is discussed.

Bacterial Proteins↗
PubMed2002

Inhibition of hyaluronan synthesis in Streptococcus equi FM100 by 4-methylumbelliferone.

As observed previously in cultured human skin fibroblasts, a decrease of hyaluronan production was also observed in group C Streptococcus equi FM100 cells treated with 4-methylumbelliferone (MU), although there was no effect on their growth. In this study, the inhibition mechanism of hyaluronan synthesis by MU was examined using Streptococcus equi FM100, as a model. When MU was added to a reaction mixture containing the two sugar nucleotide donors and a membrane-rich fraction as an enzyme source in a cell-free hyaluronan synthesis experiment, there was no change in the production of hyaluronan. On the contrary, when MU was added to the culture medium of FM100 cells, hyaluronan production in the isolated membranes was decreased in a dose-dependent manner. However, when the effect of MU on the expression level of hyaluronan synthase was examined, MU did not decrease either the mRNA level of the has operon containing the hyaluronan synthase gene or the protein level of hyaluronan synthase. Solubilization of the enzyme from membranes of MU-treated cells and addition of the exogenous phospholipid, cardiolipin, rescued hyaluronan synthase activity. In the mass spectrometric analysis of the membrane phospholipids from FM100 cells treated with MU, changes were observed in the distribution of only cardiolipin species but not of the other major phospholipid, PtdGro. These results suggest that MU treatment may cause a decrease in hyaluronan synthase activity by altering the lipid environment of membranes, especially the distribution of different cardiolipin species, surrounding hyaluronan synthase.

Cell-Free System↗
PubMed2000

Diabetes affects phospholipid content in the nuclei of the rat liver.

The aim of the present study was to examine the effect of acute streptozotocin diabetes on the content of different phospholipids and the incorporation of blood-borne 14C-palmitic acid into the phospholipid moieties in the rat liver nuclei. Diabetes was produced by intravenous administration of streptozotocin, and determinations were carried out two and seven days thereafter. Phospholipids were extracted from isolated nuclei and separated into the following fractions: sphingomyelin, phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine and cardiolipin. Following that, they were quantified and radioactivity was measured. It was found that, in comparison to non-diabetic controls, two-day diabetes reduced the total content of phospholipids in the nuclei by 9.6%. The content of phospholipids in the nuclei by 9.6%. The content of phosphatidylcholine and phosphatidylserine was reduced and the content of the remaining phospholipids was stable. The specific activity of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine and cardiolipin, based on radioactivity incorporated from 14C-palmitic acid, was elevated. Seven-day diabetes resulted in a reduction of the total phospholipid content in the nuclei by 39.4%. This was accounted for by a reduction in the content of each phospholipid fraction with the exception of cardiolipin. The specific activity of each phospholipid fraction, was elevated in this group. It is concluded that insulin is involved in the regulation of the nuclear phospholipid content.

Animals↗
PubMed1998

Purification and characterization of phosphatidylglycerolphosphate synthase from Schizosaccharomyces pombe.

The enzyme CDP-diacylglycerol:sn-glycerol-3-phosphate 3-phosphatidyltransferase (phosphatidylglycerolphosphate synthase; PGPS4; EC 2.7.8.5) is located in the mitochondrial inner membrane and catalyzes the committed step in the cardiolipin branch of phospholipid synthesis. Previous studies revealed that PGPS is the most highly regulated enzyme in cardiolipin biosynthesis in both Saccharomyces cerevisiae and Schizosaccharomyces pombe. In this work, we report the purification to homogeneity of PGPS from S. pombe. The enzyme was solubilized from the mitochondrial membrane of S. pombe with Triton X-100. The solubilized enzyme, together with the associated detergent and intrinsic lipids, had a molecular mass of 120 kDa, as determined by gel filtration. The enzyme was further purified using salt-induced phase separation, gel filtration, and ionic exchange, hydroxylapatite, and affinity chromatographies. The procedure yielded a homogeneous protein preparation, evidenced by both SDS-polyacrylamide gel electrophoresis (PAGE) and agarose isoelectric focusing under nondenaturing conditions. The purified enzyme had an apparent molecular mass of 60 kDa as determined by SDS-PAGE. The enzyme showed a strong dependence on lipid cofactors for activity in vitro. While both phosphatidic acid and CDP-diacylglycerol appeared to be activators, the most significant activation was observed with cardiolipin. The possible physiological significance of the lipid cofactor effect is discussed. This is the first purification of a eucaryotic PGPS enzyme to date, and the first purification of a phospholipid biosynthetic enzyme from S. pombe.

Cations, Divalent↗
PubMedDate not supplied

CTLA4Ig prevents initiation but not evolution of anti-phospholipid syndrome in NZW/BXSB mice.

NZW "x" BXSB F1 mice develop SLE that is associated with an anti-phospholipid syndrome characterized by anti-cardiolipin antibodies, thrombocytopenia and small coronary artery thrombosis. This syndrome is immune mediated and, dependent, on CD4+T cells. To determine whether disease in these mice can be treated with blockade of T cell costimulation we treated them with the CD28 antagonist CTLA4Ig at 9 or 12 weeks of age. CTLA4Ig completely prevented both SLE nephritis and myocardial infarcts if it was given at 9 weeks of age, before anti-cardiolipin antibodies could be detected in the serum and prevented both B cell expansion and activation and the development of peripheral monocytosis. If treatment was delayed until 12 weeks of age after cardiolipin antibodies had arisen but before the onset of clinical disease, CTLA4Ig had very little effect on disease progression. These findings indicate that CD4+T cell activation through CD28 is critical for disease initiation in this model but plays little role in disease progression or tissue damage. These findings have relevance to the treatment of anti-phospholipid syndrome in humans.

Abatacept↗
PubMed2003

Is it possible to diagnose primary anti-phospholipid syndrome (PAPS) on the basis of renal thrombotic microangiopathy (PAPS nephropathy) in the absence of other thrombotic process?

The kidneys are a major target of PAPS. The histologic lesions of PAPS nephropathy are vascular; among them thrombotic microangiopathy (TMA) is the most characteristic. It is still not clear in the literature whether the nephropathy can be the unique manifestation of PAPS in the absence of other thrombotic processes; that is: do the renal microthrombotic lesions allow to make the diagnosis of PAPS in presence of anti-phospholipid antibodies (APA)? With this purpose we present three clinical cases. The first patient had severe hypertension C4 hypocomplementemia, thrombocytopenia, and mitralic valve insufficiency. LAC and anti-cardiolipin antibodies at high titre were positive. The histologic picture was characterized by basement membrane reduplication and arteriolar mucoid degeneration, which are features of early phase of TMA. The second patient had severe hypertension. The detection of anti-cardiolipin antibodies was performed several times and resulted positive three times, four months after the diagnosis as well. The renal histologic features were consistent with late lesions of TMA. The third patient had severe hypertension, rapidly progressive renal failure, tricuspidal valve insufficiency and two positive anti-phospholipid antibodies determinations three weeks apart (in two occasions anti-cardiolipin and in one occasion LAC as well were found). The renal lesions were characteristic for TMA. In conclusion we think that patients with TMA and antiphospholipid antibodies can be considered affected by PAPS, as the thrombotic process is represented by thrombosis in preglomerular arterioles, which leads to TMA.

Acute Kidney Injury↗