Anti-CD40 antibodies in antiphospholipid syndrome and systemic lupus erythematosus

Anti-beta2glycoprotein I (anti-beta2GPI) antibodies constitute the main autoantibody specificity in the sera of patients with antiphospholipid syndrome (APS). There is evidence that anti-beta2GPI antibodies induce the precoagulant activity of the endothelium by cross-linking the beta2 glycoprotein I (beta2GPI) on the cell surface. Since beta2GPI lacks intracellular domains, homology with other molecules such as CD40 that could initiate signaling, was extensively searched. A 86% homology between the amino acid position 239-245 of the CD40 and 7-13 of the beta2glycoprotein was found. The CD40 peptide corresponding to amino acids 239-245 of the CD40 molecule was synthesized and coupled to a multiple antigenic peptide carrier. Antibodies to CD40 peptide were found in 61.5% APS patients (n = 39), in 72.7% of systemic lupus erythematosus (SLE) positive for anti-beta2GPI antibodies (n = 11) and 31.6% of SLE negative for anti-beta2GPI antibodies (n = 19), but not in rheumatoid arthritis patients (n = 28) or controls (n = 36). Antibodies to CD40 peptide were associated with arterial thrombosis and/or brain microinfarcts. Affinity purified anti-CD40 peptide antibodies as well as affinity purified anti-beta2GPI antibodies recognized both, the beta2GPI and the CD40 peptide. The specificity of this recognition was confirmed with homologous and heterologous inhibition experiments. Confocal microscopy experiments demonstrated this cross-recognition of CD40 and beta2GPI molecules, by the purified anti-CD40 peptide antibodies, at the protein level. Thus, antibodies reacting with the beta2GPI can react and potentially activate different cells which express CD40 molecules at their surface.     

Multiphasic disseminated encephalomyelitis, systemic lupus erythematosus and antiphospholipid syndrome

We report a case of multiphasic disseminated encephalomyelitis (MDEM) associated with systemic lupus erythematosus (SLE) and antiphospholipid syndrome. The initial presentation was suggestive of multiple sclerosis. Further clinical attacks, MRI imaging, and CSF findings led to a diagnosis of disseminated encephalomyelitis (DEM). Multiple episodes of neurological dysfunction, which differed in clinical presentation, further categorized the diagnosis as multiphasic DEM. The co-occurrence SLE and antiphospholipid syndrome is unusual and provided an additional diagnostic challenge.     

Fibrinolytic potential and antiphospholipid antibodies in systemic lupus erythematosus and other connective tissue disorders.

We studied the fibrinolytic response before and after venous occlusion (VO) in 30 patients with systemic lupus erythematosus (SLE), 25 with rheumatoid arthritis (RA) and 25 with different connective tissue disorders. Results were compared in patients with and without antiphospholipid antibodies (APA) and a history of either thrombosis or abortions. Before occlusion plasma levels of tissue-type plasminogen activator (t-PA) antigen and its inhibitor (PAI-1) were significantly higher in the patient group (p < 0.001). After occlusion, a low fibrinolytic activity on fibrin plates (p < 0.005) was observed in the same group. t-PA capacity and t-PA release were similar in relation to controls. The plasma PAI-1 activity was significantly elevated in each group of patients (p < 0.005) as compared to the control group. No significant differences with respect to t-PA and PAI-1 were observed in patients as to the presence or absence of thrombosis. There was also no correlation between the fibrinolytic changes and the presence of APA. It is concluded that an impairment of the fibrinolytic system, mainly related to increased PAI-1 levels, is present in most patients with connective tissue disorders, although these changes did not correlate with the presence of APA or the incidence of thrombosis.     

Kluver-bucy syndrome in systemic lupus erythematosus

Summary The Kluver-Bucy syndrome has not been previously reported as a complication of systemic lupus erythematosus (SLE). A 48-year-old female is described who sustained several cerebral infarcts, some of which were bitemporal, due to SLE vasculopathy. She developed a complex behavioural picture consisting of global aphasia, left-side neglect, hyperorality, hypermetamorphosis and hypersexuality. She displayed appropriate emotional reaction to visually presented objects, indicating that her Kluver-Bucy syndrome could not be explained by lack of visual recognition.     

Peripheral neuropathy in systemic lupus erythematosus with epineural vasculitis and antiphospholipid antibodies

Neurological manifestations of systemic lupus erythematosus are frequent and polymorphic. Their frequency varies according to authors (24-75p.cent). Central nervous system complications predominate; peripheral features are rare, classically symmetrical polyneuropathy, multiple mononeuropathies or cranial nerve involvement. We report a case of a 48-year-old woman presenting a histologically documented sensitivo-motor polyneuropathy with severe motor involvement complicating lupus associated with antiphospholipides antibodies. Outcome was good after cyclophosphamid pulse. We discuss the frequency of peripheral involvement in systemic lupus erythematosus, pathogenic mechanisms, therapeutic possibilities and outcome of this complication.     

Cerebrospinal fluid and serum antiphospholipid antibodies in multiple sclerosis, Guillain-Barré syndrome and systemic lupus erythematosus

Immunoglobulins isotypes (IgG and IgM) for myelin basic protein (MBP), cerebrosides (CER), gangliosides (GANG) and cardiolipin (CARD) were detected in the cerebrospinal fluid (CSF) from 33 patients with multiple sclerosis (MS), 18 with Guillain-Barré syndrome (GBS) and 30 with systemic lupus erythematosus (SLE). In MS patients occurred positive and significant levels of IgG-MBP in 51.5% (p less than 0.05) and IgM-MBP in only 18.2%, IgG-CARD in 46.2%, as long as CER and GANG were detected in almost 20%. From serum samples of MS patients 20.6% presented IgG-MBP, while 53% showed positive levels for IgM-MBP. The CSF analysis of patients with GBS showed that 56.3% revealed IgG-MBP (p less than 0.05), 53% for IgM-MBP, 38.5% for IgG-CER and 23% for IgM-CER, while 50% of patients had IgG-CARD, as long as 31% also had IgG-GANG. The serum evaluation from 14 patients showed that 18.8% had positive concentrations of IgG-MBP and 56.3% presented IgM-MBP (p less than 0.05). Except for 50% of patients with SLE who presented positive CSF levels of IgG-CARD, only 24.1% had positive levels of IgG-MBP. We believe that the presence of antiphospholipid antibodies in CSF of the above mentioned diseases occurred as immune epiphenomena, but their appearance would permit the maintenance of and perpetuate the immune event.     

Familial systemic lupus erythematosus and congenital infection-like syndrome

We present two siblings with congenital and progressive encephalopathy associated with systemic lupus erythematosus. The two brothers presented soon after birth with an encephalopathy associated with intracranial calcification (=2), intrauterine growth retardation (= 2), hepatitis (= 1) and thrombocytopenia (= 1), mimicking a congenital virus infection. Within the first year of life both children developed hypocomplementaemia and systemic lupus erythematosus (SLE), the main features of which were a discoid lupus-like rash on the hands and feet and the progressive production of high levels of autoantibodies. Both children were severely handicapped and died in early childhood from streptococcal infections. There are many causes of congenital encephalopathy with intracranial calcification. The early development of systemic lupus in these children suggested that their cerebral disease formed part of an autoimmune process. Complement levels and autoantibody profiles should be considered part of the investigation of a child with congenital infection-like syndrome, particularly when there are progressive dermatological complications.     

Neuropsychological functioning and its relationship to antiphospholipid antibodies in patients with systemic lupus erythematosus

While it is clear that central nervous system (CNS) lesions in systemic lupus erythematosus (SLE) adversely affect cognitive functioning, it is also evident that patients without visible lesions (non-CNS SLE) may also exhibit subtle cognitive impairment. The presence of antiphospholipid antibodies (aPLs) has been proposed as a marker of disease severity and hence should be correlated with neuropsychological dysfunction in this population. The current study compared groups of non-CNS lupus patients who were positive (LA+) or negative (LA-) for aPLs on selected measures of neuropsychological functioning. In addition, we attempted to characterize the pattern of cognitive impairment that is associated with LA status in these patients. No coherent neuropsychological pattern emerged, but LA+ patients performed worse than LA- patients on measures assessing attention, concentration, and visual search, as well as spatial learning and memory.     

Stroke in systemic lupus erythematosus

We investigated the clinical and pathologic characteristics of stroke in 234 patients with systemic lupus erythematosus. Thirteen patients (5.6%) developed cerebrovascular disease. Cerebral infarction was noted in eight, cerebral hemorrhage in two, and subarachnoid hemorrhage in three. In seven (54%) of these 13 patients, stroke occurred less than or equal to 5 years after systemic lupus erythematosus was diagnosed. Among the predisposing risk factors for stroke, hypertension was the most important. Lupus anticoagulant was detected in three (38%) and anticardiolipin antibody in three (43% of seven investigated) of the patients with infarction. Evaluation of the clinical manifestations and autoantibodies indicated that renal involvement and high titers of anti-deoxyribonucleic acid antibody were more frequent in the stroke group than in the non-stroke group. Autopsy studies on six of the patients with stroke revealed small infarcts and hemorrhages in all, but in no case was true angiitis observed. Libman-Sacks endocarditis was found in two of the three patients with infarction. In conclusion, the important contributory factor to the development of stroke in patients with systemic lupus erythematosus is considered to be hypertension mediated by immunologic abnormalities. Antiphospholipid antibodies and Libman-Sacks endocarditis are closely associated with occlusive cerebrovascular disease.     

Systemic lupus erythematosus presenting with a choreo-athetosic syndrome associated with antiphospholipid antibodies

INTRODUCTION: Chorea is a rare manifestation of systemic lupus erythematosus (1-4 percent), commonly affecting young woman. Chorea is revealing lupic disease in 50 percent, in the other cases it occurs early in the course of the disease. OBSERVATION: A 33-year-old woman was hospitalized for choreo-athetosic movements prevailing on the left leg and arm accompanied by behavioral and general state deterioration. The biological assessment consolidated the diagnosis of lupic disease associated antiphospholipides antibody (aPL). Cerebral magnetic resonance imaging (MRI) was normal except for cortical and subcortical atrophy. The patient was treated by corticosteroids (1mg/kg/day) and then was lost to follow-up. CONCLUSION: We review data in the literature on the pathophysiological mechanisms of lupic chorea focusing particularly on role of aPL.     

Transient Lambert-Eaton myasthenic syndrome associated with systemic lupus erythematosus

We present a patient who developed the Lambert-Eaton myasthenic syndrome (LEMS) in association with systemic lupus erythematosus (SLE). Severe proximal weakness with electrodiagnostic evidence of LEMS developed over 2 days during an exacerbation of cutaneous manifestations (bullous pemphigoid) associated with SLE. Following an increase in the daily dose of prednisone, there was complete clinical restitution of strength within 2 weeks and a slower resolution of electrodiagnostic abnormalities over 6 months. Marked serologic abnormalities were present at the onset and showed improvement over 6-8 months. LEMS had been infrequently described in association with SLE. The immunologic features of both SLE and LEMS suggest a linkage between the two diseases in this patient. We hypothesize that increased antibodies associated with exacerbation of SLE cross reacted with the neuromuscular junction membrane to produce LEMS.     

Myelitis in systemic lupus erythematosus

SLE-associated acute transverse myelitis (ATM) is a rare, but potentially severe complication of Systemic lupus erythematosus (SLE), and may lead to significant motor, sensory and autonomic dysfunctions in the central nervous system resulting in marked neurological deficits. It is important to recognize its clinical feature to allow timely diagnosis and management of this condition. In this review, we aimed to provide the reader with the understanding of its clinical presentation and classification, the underlying pathological, MRI (magnetic resonance imaging) appearance, and current status of management, with an emphasis on recent discoveries and advancements.     

Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: a population-based neuropsychological study

We present a cross-sectional, population-based neuropsychological study of systemic lupus erythematosus (SLE) patients identified within Tampere University Hospital district, Finland with 440,000 inhabitants. Patients with definite SLE in the age range of 16-65 years (n = 46) and matched controls (n = 46) underwent neurological examination and comprehensive neuropsychological testing. On the basis of medical examination, the SLE patients were divided into neuropsychiatric (NP+; n = 15) and nonneuropsychiatric (NP-; n = 31) cases. The neuropsychological test results revealed more prevalent cognitive impairment in the NP+ patients, indicating that this subgroup mostly accounts for neuropsychological changes in SLE. Most characteristic changes in NP+ were observed in domains of memory, psychomotor speed, and complex attention. This suggests nonspecific CNS involvement, which is in line with neurological manifestations of the disease.