Elevated levels of soluble CD40 ligand are associated with antiphospholipid antibodies in patients with systemic lupus erythematosus.

OBJECTIVES: The CD40L/CD40 pathway is involved in the pathophysiology of atherothrombotic disease, and elevated levels of soluble CD40L (sCD40L) were reported in SLE patients. However, the clinical implication of sCD40L in SLE remains elusive. METHODS: We measured levels of plasma sCD40L in 241 SLE patients and 37 healthy controls and investigated its association with clinical manifestation and laboratory parameters. RESULTS: Levels of plasma sCD40L in SLE patients were significantly elevated compared with healthy controls (p=0.013) and positively correlated with levels of soluble P-selectin (γ=0.336, p<0.001). SLE patients who experienced arterial thrombosis had a higher level of sCD40L than those who did not (p=0.029). Plasma sCD40L levels were positively correlated with the titers of anti-cardiolipin and anti-ß2 glycoprotein I antibodies (γ=0.338, p<0.001 and γ=0.364, p<0.001, respectively). Its levels were also significantly higher in patients with clinical antiphospholipid syndrome (APS) than in non-APS patients, irrespective of antiphospholipid antibody (aPL) positivity. Of those with arterial thrombosis, sCD40L levels were significantly elevated in patients with positive aPL, compared to those with negative aPL (p=0.011). Multiple regression analysis revealed that the presence of hypertension and positive aPL were independently associated with the occurrence of arterial thrombosis in SLE patients. A parallel analysis showed that sCD40L was also an independent variable for arterial thrombosis; however, this association disappeared when aPL, a strong variable, was included in the model because of collinearity between aPL and sCD40L. CONCLUSIONS: Plasma sCD40L levels were elevated in SLE patients who had positive aPL and experienced arterial thrombosis, suggesting that enhanced release of sCD40L through platelet activation presumably by aPL could contribute to the development of atherothrombotic disease.

Diagnosis of catastrophic anti-phospholipid syndrome in a patient tested negative for conventional tests.

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of APS, characterised by clinical evidence of multiple organ involvement developing over a very short period of time, histopathological evidence of multiple small vessel occlusions and laboratory confirmation of the presence of aPL (lupus anticoagulant and/or anticardiolipin antibodies and/or anti-Beta2-glcyoprotein I antibodies). Here we report a case of a 39-year-old woman patient who developed a CAPS which was negative to the conventional aPL but positive for aPL in thin layer chromatography immunostaining and vimentin/cardiolipin antibodies by ELISA test. The patient was treated with high doses of glucocorticoids, intravenous immunoglobulins plasma exchange and immunoadsorbent apheresis with a significant improvement of the ischaemic lesions of the hands even though the necrosis of the feet progressively worsened. As a result, the patient underwent partial surgical amputation of the feet. To our knowledge, this is the first ever reported case of CAPS diagnosed by means of thin layer chromatography immunostaining and vimentin/cardiolipin antibody ELISA test.

Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-α and IL-6 receptor targeted therapies in refractory Takayasu arteritis.

OBJECTIVES: We analysed a large cohort of patients with Takayasu arteritis, seeking robust clinical evidence for prolonged responses to tumour necrosis factor-α (TNF-α) and interleukin-6 receptor (IL-6R) antagonists in severe refractory disease. METHODS: Case notes from ninety-eight patients with Takayasu arteritis were retrospectively reviewed. Drug treatment, laboratory and serial non-invasive imaging data were analysed, and the Indian Takayasu arteritis activity (ITAS) and damage scores (TADs) calculated. RESULTS: Nine patients were treated with biologic therapies. All had previously received high dose prednisolone and ≥1 conventional immunosuppressant. Five patients had failed cyclophosphamide. The patients prescribed biologics had more extensive arterial injury than the remainder of the cohort and persistent active disease (ITAS range 2-9, CRP 12-206 mg/L, TADs 3--1). Eight patients were prescribed anti-TNF-α therapy, three IL-6R blockade. The mean duration of anti-TNF-α treatment was 42 months (maximum 8 years). One patient developed new arterial stenoses while receiving anti-TNF-α and subsequently achieved disease remission with tocilizumab. Two patients have now demonstrated sustained responses to IL-6R inhibition at 19 and 20 months. Following introduction of biologic therapy, serial non-invasive imaging has revealed no significant progression in arterial injury. A significant fall in CRP (p<0.01), prednisolone dose (p<0.01) and ITAS (p<0.01) was observed, with no increase in TADs. CONCLUSIONS: We report for the first time sustained responses to both anti-TNF-α and IL6R antagonists in refractory Takayasu arteritis. As 5/9 patients were cyclophosphamide non-responders, we propose that biologics should now be considered ahead of cyclophosphamide in these young patients.

Ulnar artery occlusion is predictive of digital ulcers in SSc: a duplex sonography study.

OBJECTIVES: To assess the prevalence and risk factors of ulnar artery occlusion (UAO) in an unselected SSc patient cohort and to determine whether UAO is associated with digital ulcers (DUs). METHODS: A total of 79 SSc patients and 40 'healthy' controls underwent colour duplex sonography of the radial and ulnar artery to compare blood flow velocity, resistive indices (RIs) and presence of occlusion and were followed for a mean of 53 months. RESULTS: In both, radial and ulnar arteries, peak systolic velocity (PSV) and end-diastolic velocity (EDV) were significantly lower and RI higher in SSc patients compared with controls (PSVrad: 40.1 vs 48.6 cm/s; PSVuln 38.2 vs 56.6 cm/s; EDVrad 3.8 vs 10.4 cm/s; EDVuln 3.0 vs 13.0 cm/s; RIrad 0.91 vs 0.82; RIuln 0.92 vs 0.80; all P < 0.01). Seventeen (21.5%) SSc patients had UAO (11 patients bilateral) compared with none in the control subjects. Patients with UAO had a significantly longer disease duration (170 vs 66 months, P < 0.001). At baseline, the prevalence of DU was not different in upper extremities with UAO [8/28 (28.6%)] compared with upper extremities without UAO [36/129 (27.9%)]. However, during follow-up new or recurrent DU occurred more often in upper extremities with UAO than in those without UAO [14/28 (50%) vs 24/113 (21.2%); relative risk (RR) = 2.4; 95% CI 1.4, 3.7; P = 0.002]. CONCLUSION: Blood flow is significantly decreased in radial and ulnar arteries in SSc. UAO is frequent and an important risk factor for the development of DUs in patients with SSc.

Castleman's disease and arterial thrombosis: result of excessively elevated interleukin-6 plasma level?

Morbus Castleman is a benign non-clonal lymphoproliverative disorder. Immunomodulatory and antiproliferative drugs are used to treat this plasma cell disorder. We report the case of a 46-year old female patient with multicentric Castleman's disease and limb ischemia. Thrombotic occlusions of the popliteal and tibioperoneal arteries were treated by percutaneous thrombus aspiration. We discuss the role of increased interleukin-6 plasma levels during therapy with Tocilizumab, an antibody to interleukin-6 receptor, as a potential cause for arterial thrombosis.

Free flap failure in an anticardiolipin antibody-positive patient with neoplasm--a case report.

We present herein a case of massive arterial thrombosis of a free rectus abdominal musculocutaneous flap used for reconstructive surgery of gingival carcinoma that could not be rescued. A 54-year-old woman underwent the operation. She had experienced two miscarriages in her 20s, but medical history was otherwise uneventful. Intraoperatively, the anastomosed artery often showed massive arterial thrombosis, and the flaps had become necrotic after bilateral flaps were used. Laboratory findings, 7 days postoperatively, showed high levels of immunoglobulin G anticardiolipin antibody. This value normalized by 2 months postoperatively after using chemotherapy. This case does not match the criteria for antiphospholipid syndrome, but some English-language reports have shown rising antiphospholipid antibody levels, particularly anticardiolipin antibodies, in patients with neoplasm. In those cases, levels have normalized after successful therapy. Antiphospholipid antibody levels should be examined before surgery to identify risks of hypercoagulability.

The role of chemokines in transplant graft arterial disease.

Despite the development of effective immunosuppressive therapy, transplant graft arterial disease (GAD) remains the major limitation to long-term graft survival. Multiple immune and nonimmune risk factors contribute to this vasculopathic intimal hyperplastic process. Thus, initial interplay between host inflammatory cells and donor endothelial cells triggers alloimmune responses, whereas alloantigen-independent factors such as prolonged ischemia, surgical manipulation, ischemia-reperfusion injury, and hyperlipidemia enhance the antigen-dependent events. Intrinsic to all stages of this process are chemokines, a family of 8- to 10-kDa proteins mediating directional migration of immune cells to sites of inflammation and injury. Beyond their role in immune-cell chemotaxis, chemokines also contribute to cellular activation, vascular remodeling, and angiogenesis. Expression of chemokines and their cognate receptors in allografts correlates with acute organ rejection, as well as GAD. Moreover, chemokine or chemokine receptor blockade prolongs graft survival and attenuates GAD in experimental models. Further studies will likely confirm a substantial utility for antichemokine therapy in human organ transplantation.

Deficiency of tumour necrosis factor-alpha and interferon-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury.

AIMS: Neointimal formation after percutaneous coronary intervention (PCI), termed restenosis, limits therapeutic revascularization. Since it is now known that vascular injury involves an inflammatory response, we examined the role of tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the neointimal formation after injury. METHODS AND RESULTS: Control (BALB/c), TNF-alpha-deficient (Tnf(-/-)), IFN-gamma-deficient (Ifng(-/-)), or double-deficient (Tnf(-/-)Ifng(-/-)) mice were subjected to wire-mediated vascular injury of the right femoral artery. Neointimal formation after injury was significantly reduced after the injury in the Tnf(-/-)Ifng(-/-) mice, compared to that in the control, Tnf(-/-), and Ifng(-/-) mice. Immunohistochemical analysis showed that TNF-alpha and IFN-gamma were expressed in neointimal lesions in the control mice, but not in mice with deficiency of the corresponding cytokine. No significant difference in re-endothelialization was observed among these groups. The number of proliferating cell nuclear antigen in the neointimal lesions was significantly decreased in the Tnf(-/-)Ifng(-/-) mice. Bone marrow transplantation experiments revealed that deficiency of TNF-alpha and IFN-gamma specifically in bone marrow cells significantly inhibited neointimal formation after vascular injury. CONCLUSION: The absence of TNF-alpha and IFN-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury, and thus, may provide new insights into the mechanisms underlying restenosis after PCI.

Circulating endothelial progenitor cells decrease in patients after endarterectomy.

BACKGROUND: Endothelial progenitor cells (EPC) contribute to vascular regeneration. Since surgical injury and burns induce a pro-inflammatory and proangiogenic response, we investigated the effect of vascular injury with minimal surgical trauma after endarterectomy on the number of circulating EPC and systemic inflammatory changes. METHODS AND RESULTS: Forty-five patients with peripheral arterial occlusive disease were included in the study. Venous blood samples were taken before and 1 day after endarterectomy and plaque material was obtained. Ten patients with minor surgery served as controls. Circulating CD133+CD34+, VEGFR-2+CD34+ progenitor cells and surface expression of CD11b on circulating neutrophils were analysed using flow cytometry. EPCs were characterized in a culture assay as double-positive for DiI-LDL uptake and lectin binding. Cytokine concentrations of interleukin (IL)-6, IL-8, TNF-alpha, IL-1ss, IL-10, IL-12, SDF-1, G-CSF, and VEGF were measured in plasma and tissue samples. After endarterectomy a significant decrease in circulating EPC, CD133+CD34+, and VEGFR-2+CD34+ cells was observed. This was associated with a specific pattern of changes in circulating cytokine levels after endarterectomy with a decrease in IL-1 beta and IL-12, an increase in IL-6 and G-CSF plasma concentrations, and surface expression of CD11b on circulating neutrophils. In contrast, after minor surgery an increase in circulating CD133+CD34+ cells, IL-6, IL-8, and IL-10 was found. Interestingly there was a negative association between levels of local IL-6 within the plaque and only the preoperative levels of circulating CD133+C34+. CONCLUSION: Endarterectomy induces changes in circulating cytokines and a decline in circulating progenitor cells, which may be due to recruitment of progenitor cells to the injured vessels. This is supported by the negative association between plaque inflammation and circulating progenitor cells before endarterectomy.

Natural killer cells and CD4+ T-cells modulate collateral artery development.

OBJECTIVE: The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. METHODS AND RESULTS: Lymphocytes, detected with markers for NK1.1, CD3, and CD4, invaded the collateral vessel wall. Arteriogenesis was impaired in C57BL/6 mice depleted for Natural Killer (NK)-cells by anti-NK1.1 antibodies and in NK-cell-deficient transgenic mice. Arteriogenesis was, however, unaffected in J alpha281-knockout mice that lack NK1.1+ Natural Killer T (NKT)-cells, indicating that NK-cells, rather than NKT-cells, are involved in arteriogenesis. Furthermore, arteriogenesis was impaired in C57BL/6 mice depleted for CD4+ T-lymphocytes by anti-CD4 antibodies, and in major histocompatibility complex (MHC)-class-II-deficient mice that more selectively lack mature peripheral CD4+ T-lymphocytes. This impairment was even more profound in anti-NK1.1-treated MHC-class-II-deficient mice that lack both NK- and CD4+ T-lymphocytes. Finally, collateral growth was severely reduced in BALB/c as compared with C57BL/6 mice, 2 strains with different bias in immune responsiveness. CONCLUSIONS: These data show that both NK-cells and CD4+ T-cells modulate arteriogenesis. Promoting lymphocyte activation may represent a promising method to treat ischemic disease.

Leukotriene B4-Mediated Neutrophil Recruitment Causes Pulmonary Capillaritis during Lethal Fungal Sepsis.

Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C. albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C. albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival. However, complement activation also leads to Leukotriene B4 (LTB4)-mediated intravascular PMN clustering and occlusion, resulting in capillaritis with pulmonary hemorrhage and hypoxemia. This clustering is unique to fungi and triggered by fungal cell wall components. PMN clustering is absent in mice lacking LTB4-receptor, and capillaritis is attenuated upon pharmacological LTB4 blockade without affecting phagocytosis. Therefore, therapeutically disrupting infection-induced capillaritis may limit organ injury without impairing host defense during fungal sepsis.

Antiphospholipid syndrome and vascular ischemic (occlusive) diseases: an overview.

Antiphospholipid syndrome (APS) is primarily considered to be an autoimmune pathological condition that is also referred to as "Hughes syndrome". It is characterized by arterial and/or venous thrombosis and pregnancy pathologies in the presence of anticardiolipin antibodies and/or lupus anticoagulant. APS can occur either as a primary disease or secondary to a connective tissue disorder, most frequently systemic lupus erythematosus (SLE). Damage to the nervous system is one of the most prominent clinical constellations of sequelae in APS and includes (i) arterial/ venous thrombotic events, (ii) psychiatric features and (iii) other non- thrombotic neurological syndromes. In this overview we compare the most important vascular ischemic (occlusive) disturbances (VIOD) with neuro-psychiatric symptomatics, together with complete, updated classifications and hypotheses for the etio-pathogenesis of APS with underlying clinical and laboratory criteria for optimal diagnosis and disease management.

The presence of anti-phosphatidylserine/prothrombin antibodies as risk factor for both arterial and venous thrombosis in patients with systemic lupus erythematosus.

In an effort to clarify the clinical significance of anti-phospholipid antibodies (aPL) detected by enzyme-linked immunosorbent assay (ELISA), we examined the prevalence of anti-cardiolipin antibodies (aCL), anti-beta2-glycoprotein I antibodies (anti-beta2-GPI), antiprothrombin antibodies (anti-PT), and anti-phosphatidylserine/prothrombin antibodies (anti-PS/PT) in 175 patients with systemic lupus erythematosus (SLE) comprising 67 patients with thrombotic complications. The present study showed that positive results of anti-beta2-GPI-ELISA and anti-PS/PT-ELISA could serve as markers of thrombotic complications in patients with SLE, whereas aCL and anti-PT are less reliable as markers of these complications. Furthermore, results of the anti-PS/PT-ELISA correlate best with the occurrence of both arterial and venous thrombosis in patients with SLE.

Myocyte enhancer factor 2 mediates vascular inflammation via the p38-dependent pathway.

Although it has been established that myocyte enhancer factor 2 (MEF2) plays pivotal roles in the development of the cardiovascular system as well as skeletal muscle cells, little is known of its role in vascular inflammatory diseases such as atherosclerosis and restenosis after angioplasty. To investigate the role of MEF2 in vascular inflammation and that of p38 in the activation of MEF2, we infected cultured rat vascular smooth muscle cells (VSMCs) with an adenovirus construct expressing a dominant-negative mutant of MEF2A (MEF2ASA) or mitogen-activated protein kinase kinase 6 (MEK6AA), and examined their effects on the expression of monocyte chemoattractant protein-1 (MCP-1), which is known to play important roles in vascular inflammation. We also examined the role of MEF2 in vivo using a rat model of transluminal wire-induced injury of the femoral artery. Angiotensin II (Ang II)-induced expression of MCP-1 mRNA was significantly inhibited by infection with adenoviruses encoding MEF2ASA (AdMEF2ASA) or MEK6AA. Ang II-induced increase of MCP-1 promoter activity was also significantly suppressed by overexpression of MEF2ASA or MEK6AA. Ang II stimulated the transactivating function of MEF2A and this activation was inhibited by overexpression of MEK6AA. Infection with AdMEF2ASA suppressed MCP-1 expression in the femoral artery after the transluminal mechanical injury. AdMEF2ASA infection also inhibited macrophages infiltration and neointimal formation in the wire-injured femoral arteries. These results suggested that MEF2 activation via the p38-dependent pathway mediates vascular inflammation via stimulation of MCP-1 expression in VSMCs and macrophages infiltration.

Differences between arterial occlusive and cortical photothrombosis stroke models with magnetic resonance imaging and microtubule-associated protein-2 immunoreactivity.

The differences between two models of cerebral ischemia [middle cerebral arterial transection (MCAT) and cortical photothrombosis (PT)] were explored with multiparametric MRI of apparent diffusion coefficient trace (ADCtr), cerebral blood flow (CBF) and T1. Microtubule-associated protein-2 (MAP2) immunoreactivity sections aligned with the MR images in the same coronal plane were used to map the infarct and to guide region-of-interest selection. In ischemic cortex, the larger T1 increase in PT versus MCAT (42+/-7% vs. 16+/-5%) is related to the different character of edema between these models; yet, neither CBF nor ADCtr discriminated between them at 3.5 h, suggesting that different mechanisms of ischemic damage to the brain cells resulted in the same ADCtr value. CBF and ADCtr were depressed in immediately adjacent ischemic border by 27+/-7% and 47+/-10%, respectively, in MCAT but not in PT, suggesting marginal perfusion in MCAT. CBF in homotopic normal cortex in the opposite hemisphere was higher for PT compared with MCAT (199+/-20 and 134+/-10 ml/100 g/min, respectively). Different pathological processes in the two models affect CBF, ADCtr and T1 in a unique, regionally specific manner. The PT model differs substantially from the MCAT and is not a model of cortical ischemia with an appreciable border zone.

Endothelial progenitor cells are decreased in blood of cardiac allograft patients with vasculopathy and endothelial cells of noncardiac origin are enriched in transplant atherosclerosis.

BACKGROUND: Recent studies in animals suggest that circulating recipient endothelial precursors may participate in the biology of transplant vasculopathy. It is currently unknown whether a similar interaction between recipient endothelial cells and the vessel wall occurs in human subjects undergoing allogeneic cardiac transplantation. METHODS AND RESULTS: Circulating endothelial cells and endothelial progenitor cells (EPCs) were quantified in 15 cardiac transplantation subjects with and without angiographic evidence of vasculopathy. In a separate series of experiments, the origin (donor or recipient) of transplant plaque endothelial cells was assessed in subjects who had undergone a gender-mismatched cardiac transplantation and had histological evidence of severe vasculopathy at the time of heart explantation. Circulating EPC outgrowth colonies in peripheral blood were significantly reduced in subjects with transplant vasculopathy compared with those without angiographic evidence of disease (EPC colony-forming units [CFUEPC]: 4.5+/-1.9 versus 15.1+/-3.7, P<0.05). There was no significant difference in circulating endothelial cell numbers as defined by day 4 culture acetylated LDL/lectin assay in either of these patient groups. In a separate group of 5 subjects who underwent gender-mismatched cardiac transplantation, there was a significant seeding of recipient endothelial cells (range: 1% to 24% of all luminal endothelial cells) in large-vessel lumen and adventitial microvessel lumen of arteriopathic vessels. No opposite-sex chimeric cells were observed in control gender-matched transplantation scenarios. CONCLUSIONS: These data suggest that the human cardiac transplant arteriopathy is associated with reduction in circulating endothelial precursors and with seeding of recipient-derived endothelial cells at the site of plaque development.

Inhibition by leukocyte depletion of neointima formation after balloon angioplasty in a rabbit model of restenosis.

OBJECTIVE: The aim of the current study was to examine neointima formation in balloon injured left subclavian artery of rabbits subjected to two different methods of leukocyte depletion at the time of injury. METHODS: Angioplasty of the left subclavian artery was performed in leukopenic male New Zealand White rabbits. Depletion of circulating leukocytes was induced by either mustine hydrochloride or an antibody against leukocyte common antigen (anti-LCA) before angioplasty. Left and right subclavian arteries were removed 28 days after injury for morphological analysis and measurement of neointimal size. At the same time, leukocytes were isolated from autologous rabbit blood for 51Cr-labelling for assessment of leukocyte adhesion to injured and non-injured artery segments. RESULTS: Leukopenia decreased neointima formation in injured arteries (neointimal area was 0.09+/-0.03 mm(2) in mustine-treated arteries, n=8, vs. 0.56+/-0.07 mm(2) in control arteries, n=7; P<0.001 and 0.07+/-0.01 mm(2) in anti-LCA treated arteries, n=9, vs. 0.22+/-0.04 mm(2) in non immune serum-treated arteries, n=9; P<0.001). Adventitial fibrosis was also significantly (P<0.05) decreased by both leukopenic interventions. Neither medial nor adventitial area was modified in any of the groups. No differences in leukocyte adhesion were observed between injured and non-injured arteries in any of the experimental groups at the 28 day time point. CONCLUSION: These results suggest that leukocytes play a major role in the development of two of the major characteristics of the response to balloon injury, namely formation of neointima and adventitial fibrosis, that currently limit the success of clinical angioplasty. Elucidation of the fine mechanisms involved in leukocyte-mediated injury may lead to the discovery of novel therapeutic targets for the prevention of restenosis.

Anticardiolipin antibodies in Sneddon's syndrome.

We studied 24 patients (18 women, 6 men), aged 29 to 54, with Sneddon's syndrome. The clinical picture of Sneddon's syndrome was characterized by cerebrovascular disorders, livedo reticularis, disturbance of peripheral circulation, arterial hypertension, cardiac pathology (ischemic heart disease, heart murmurs), complicated obstetric history in women, and disturbed sexual function in men. In 6 of 17 examined patients with Sneddon's syndrome there was a high concentration of anticardiolipin antibodies (ACA) but no antibodies to native DNA and LE cells. The course of the disease in the patients with a high ACA level, when compared with normal ACA level patients, was characterized by a more rapid progression and more severe clinical manifestations. The study demonstrates the similarity of clinical symptoms and immunologic disturbances in Sneddon's syndrome and the antiphospholipid syndrome and suggests the importance of ACA in the pathogenesis of some cases of Sneddon's syndrome.

Free and complexed anti-lipoprotein antibodies in vascular diseases.

The cell-mediated immune response against low density lipoproteins (LDL) was demonstrated by the migration inhibition test in patients with various vascular diseases. Anti-high density lipoprotein2 (HDL2) cellular immune response was found only in a few patients. LDL and HDL2 binding factors were detected in about 50% of coronary patients. No significant difference in their occurrence was found between the normolipidemic and hyperlipidemic patients nor between patients with hyperlipidemia type II/b and type IV. On the assumption that lipoproteins may act as auto-antigens by forming immune complexes, the presence of anti-LDL and anti-HDL2 activity was investigated in circulating immune complexes obtained by polyethylene glycol (PEG) precipitation from the sera of coronary patients and controls. Using an ELISA technique, PEG-precipitable anti-LDL activity was detected in 23, 11 and 18% of cases with myocardial infarction, angina pectoris and healthy old subjects, respectively. In the immune complexes obtained from the sera of the healthy young donors no anti-LDL activity was found. Anti-HDL2 activity in the immune complexes was demonstrated only in a few cases from among the patients and elderly persons we investigated.