Detection of antiphospholipid antibody in children with Henoch-Schönlein purpura and central nervous system involvement.

To explore the mechanisms of central nervous system involvement in children with Henoch-Schönlein purpura, levels of lupus anticoagulant, anticardiolipin antibodies, and anti-ß2 glycoprotein I antibodies in serum and cerebrospinal fluid were determined in 46 cases of Henoch-Schönlein purpura with central nervous system involvement. Results indicated that Henoch-Schönlein purpura with central nervous system involvement produced a higher total percentage of antiphospholipid antibodies in serum and cerebrospinal fluid, compared with viral encephalitis control subjects (76.1% vs 10.0% and 71.7% vs 0.0%, respectively; P < 0.05). Henoch-Schönlein purpura may be associated with antiphospholipid syndrome or antiphospholipid antibodies, which may account for the neurologic damage in Henoch-Schönlein purpura.

[Immunological markers of severity and outcome of traumatic brain injury].

A microscopic immunological study of cerebral spinal fluid (CSF) of 100 patients with traumatic brain injury (TBI) of different severity was carried out in the 1st, 10th and 21st days after trauma. The content of antibodies to basic myelin protein (BMP) and phospholipids (PL) significantly differed from that in the control group (patients with soft tissue head injuries without TBI) and was significantly higher in patients with severe TBI. The level of antibodies to BMP in the CSF was strongly correlated with scores on the Glasgow Coma Scale in the 1st day after TBI and the degree of recovery of neurological status in the 21st day. The level of antibodies to PL was strongly correlated with the severity of cytosis, content of CSF erythrocytes and proteins. The correlation between antibodies to BMP and antibodies to PL was weak. The different diagnostic value of antibodies to BMP and to PL in the most acute period of TBI was found. In conclusion, content of antibodies to BMP may be used as a marker of TBI severity and outcome while the significant elevation of antibodies to PL indicates the severity of vascular complications of trauma.

[Clinical characteristics and presence of antiphospholipid antibodies (anticardiolipin-beta2GP-1) cerebrospinal fluid and serum of in a series of patients with multiple sclerosis in Mexico]. / Características clínicas y anticuerpos antifosfolipídicos (anticardiolipina-beta2GP-1) en líquido cefalorraquídeo y suero en una muestra de pacientes con esclerosis múltiple en México.

INTRODUCTION: The differential diagnosis of multiple sclerosis (MS) includes a wide variety of autoimmune diseases (systemic lupus erythematosus, Sjögren syndrome, antiphospholipid syndrome, etc.). The presence of antiphospholipid antibodies (APLA) in serum of MS patients has been reported to be as low as 10%, or sometimes as high as 88% of the cases, although its significance in the pathogenesis of the disease, or its diagnostic usefulness is still unknown. The goal of this study was to describe the clinic and demographic characteristics of a sample of patients with MS from the Hospital General de México (HGM), as well as to determine the presence and frequency of APLA in cerebrospinal fluid (CSF) and serum samples of these patients. PATIENTS AND METHODS: A prospective study with patients from the Neurology Department at the HGM was performed. These patients were diagnosed with MS over a one-year period. Clinical and demographic characteristics were compiled. VDRL and anti-cardiolipin-beta2GP-1 complex antibodies were analyzed in CSF and serum samples. RESULTS: Twelve patients were included in the study, the majority females (58%). The predominant clinic feature was optic neuritis (66.6%) followed by medullary involvement (58%). Most of patients were ambulatory (< 4 EDSS points). Auto-antibody levels were found in negative ranges in all cases, both in CSF and serum. CONCLUSIONS: The clinical-demographic characteristics in patients studied in this work were similar to those previously reported, and the levels of anti-cardiolipin-beta2GP-1 were negative, thus indicating the existence of different clinical and demographic variables influencing their detection.

Anti-phospholipid antibodies in cerebrospinal fluid but not serum from a boy with psychosis.

A 12-year-old African American boy with mental retardation and Asperger's disorder presented with acute psychosis. Antiphospholipid antibody testing with enzyme-linked immunosorbent assay showed increased levels of immunoglobulin G anticardiolipin antibodies in the cerebrospinal fluid, but not in the serum. Although antiphospholipid antibodies have been reported in the serum of patients with thrombotic and neurologic disorders, there are only a few reports of these antibodies in cerebrospinal fluid. This finding is consistent with a recent report of antiphospholipid antibodies found in the cerebrospinal fluid of adults with acute psychosis.

Redox-reactive autoantibodies in cerebrospinal fluids.

The oxidative stress associated with increased transitional metal concentrations in neurodegenerative diseases served as the impetus for our testing the status of redox-reactive autoantibodies in the cerebrospinal fluids from autopsy-confirmed Alzheimer's patients. Here we describe a novel family of autoantibodies capable of recognizing autoantigens subsequent to in vitro oxidation-reduction (redox) reactions in the blood and spinal fluids of all normal individuals tested. Redox autoantibodies are not detected in conventional immunoassays, thereby differentiating them from natural and hidden autoantibodies described by others. Whereas blood-borne redox autoantibodies can be IgG, IgM, and/or IgA, in spinal fluid the antibody isotype is limited to IgG. Autoantibodies in certain patients are reversible and disappear when exposed to oxidizing agents in vitro. One mechanism proposed to modulate the autoantibody unmasking-masking reactions relies upon redox-driven nitrosylation of an amino acid-containing aromatic ring, which is found within the complementarity-determining regions (CDR) of the antibodies' antigen-binding sites. The evolutionary persistence of this novel autoantibody family indicates that they are important for immunological homeostasis and suggests that they perform necessary physiological functions. The dramatic difference in the presence of such antibodies in normal versus Alzheimer's disease (AD) suggests an important immune system dysfunction in AD.

Redox-reactive autoantibodies in Alzheimer's patients' cerebrospinal fluids: preliminary studies.

Oxidation of cerebrospinal fluid (CSF) causes differential unmasking of autoantibodies in control CSF vs. that obtained from postmortem CSF samples from autopsy confirmed Alzheimer's disease (AD) cases. This study demonstrates that normal CSF from both living patients and from non-demented autopsy cases contains redox-reactive autoantibodies with specificities that include antiphospholipid antibodies (aPL). In contrast, CSF from autopsy confirmed AD subjects contained little or no redox-reactive aPL autoantibodies. Tests using an in vitro rat synaptosome model showed that the oxidized CSF autoantibodies from a normal individual can cause ERK1/2 phosphorylation at a level consistent with reports of pathogenic changes found in brain tissues from AD patients. The decrease or absence of redox-reactive antibodies in CSF from Alzheimer's patients suggests that these antibodies may have been previously unmasked by the oxidative conditions that exist in the CNS in AD patients. These unmasked autoantibodies could then bind to neuronal tissues and possibly participate in the initial cascade leading to the dementia in Alzheimer's. To our knowledge, this is the first description of resident autoantibodies with the potential to cause brain cell damage documented in CSF without a breech in the blood-brain barrier. The untimely and inappropriate physiological unmasking of these redox-reactive autoantibodies in AD patients CSF may represent a valuable biomarker for diagnosis and progression of this and perhaps other neurodegenerative diseases which also have oxidative stress components. These novel autoantibody observations may stimulate thoughts about additional therapeutic approaches and warrant similar studies for other neurodegenerative diseases.

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.

Cerebrovascular and neurological disorders associated with antiphospholipid antibodies in CSF and serum.

Paired serum and cerebrospinal fluid (CSF) samples from 70 patients with inflammatory and non-inflammatory neurological diseases, as well as 10 sera from patients with primary antiphospholipid syndrome (PAS), six of which presented with cerebrovascular ischemic syndromes, were studied for the presence of anticardiolipin antibodies (ACA) of the G and M classes. PAS sera and some selected paired CSF and serum specimens, were also analyzed for the presence of anti-phosphatidylserine (PS) and anti-phosphatidylethanolamine (PE) antibodies. High levels of IgG and IgM ACA were synthesized intrathecally only in patients with neurosyphilis. Patients with other infectious or inflammatory neurological diseases very rarely showed detectable levels of ACA in serum and/or CSF. ACA were found not only in patients with untreated PAS but also in the serum of 3/7 patients with migraine, thus confirming a relationship between ACA and vascular disorders. The search for PS and PE antibodies disclosed that in PAS patients the serum titers of these antibodies mirrored ACA IgG and IgM titers, while they were never found in the CSF.