Mieczysław Wender

Increased serum levels of soluble PECAM-1 in multiple sclerosis patients with brain gadolinium-enhancing lesions

Platelet endothelial cell adhesion molecule, PECAM-1 (CD31) is a 130-kDa glycoprotein, member of the immunoglobulin superfamily, which is involved in transendothelial migration of leukocytes. It is expressed on endothelial cells, lymphocytes, monocytes, neutrophils, basophils and platelets. We present data showing that soluble PECAM-1 is significantly increased in sera of multiple sclerosis patients with active, gadolinium enhancing lesions. Since we have found increased levels of sPECAM-1 in sera of patients with active MRI lesions, but not in those of patients without enhancing lesions, the molecule may be regarded as marker of MS activity. Soluble PECAM-1 may be involved in immunomodulatory mechanism leading to inhibition of migration of leukocytes in MS.

Acute disseminated encephalomyelitis (ADEM)

ADEM is a disease that is characterized by an inflammatory reaction and demyelination in the central nervous system, with a distinct tendency to a peripheral localization of pathological changes. ADEM happens to occur with a temporal, and probably also with a causative relationship to viral, exanthematous diseases, as well as to preventive vaccinations. However, there are still many unresolved problems with respect to the relationship of ADEM to multiple sclerosis (MS), especially in instances with a multiphasic course of the disease. Many question marks can also be raised in cases, in which the examinations were unable to determine the exact preceding or causative factor. A lot of studies on cytokines and chemokines in blood plasma and CSR from patients with ADEM have enabled investigators to get a better insight into some stages of immunopathological processes, leading to an evolvement of the disease, without a more important impact on the clinical diagnosis.

Two novel presenilin 1 gene mutations connected with frontotemporal dementia-like clinical phenotype : Genetic and bioinformatic assessment

Mutations in the amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) genes are associated with early-onset familial Alzheimers disease (EOAD). There are several reports describing mutations in PSEN1 in cases with frontotemporal dementia (FTD). We identified two novel mutations in the PSEN1 gene: L226F and L424H. The first mutation was detected in a patient with a clinical diagnosis of FTD and a post-mortem diagnosis of AD. The second mutation is connected with a clinical phenotype of variant AD with strong FTD signs. In silico modeling revealed that the mutations, as well as mutations used for comparison (F177L and L424R), change the local structure, stability and/or properties of the transmembrane regions of the presenilin 1 protein (PS1). In contrast, a silent non-synonymous substitution F175S is eclipsed by external residues and has no influence on PS1 interfacial surface. We suggest that in silico analysis of PS1 substitutions can be used to characterize novel PSEN1 mutations, to discriminate between silent polymorphisms and a potential disease-causing mutation. We also propose that PSEN1 mutations should be considered in FTD patients with no MAPT mutations.

Multiple sclerosis-associated virus-related pol sequences found both in multiple sclerosis and healthy donors are more frequently expressed in multiple sclerosis patients

In the etiopathogenesis of multiple sclerosis (MS), both genetic and environmental factors play an important role. Among environmental factors, viral infections are most likely connected with the etiology of MS. There are many evidence suggesting possible involvement of retroviruses in the development of autoimmune diseases including MS. Multiple sclerosis-associated retrovirus (MSRV) seems to be the important candidate for viral etiology of MS. The aim of the study was to analyze MSRV pol sequences in patients with MS. As control, groups of myasthenia gravis, Parkinson’s disease, and migraine patients, and healthy individuals have been studied. The MSRV pol sequences have been analyzed in RNA isolated from the serum and in DNA and RNA of peripheral blood lymphocytes from untreated MS patients and control groups. The MSRVpol sequences have been detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and PCR technique, using specific oligonucleotide primers. In the serum RNA (cDNA), MSRV pol sequences have been identified in 31/32 MS patients. MSRV pol sequences were detected in serum cDNA of 9/17 myasthenia gravis patients, 7/16 Parkinson’s disease patients, 10/21 migraine patients, and 13/27 healthy individuals. MSRV pol sequences were observed also in RNA from lymphocytes of all MS patients, 12/17 myasthenia gravis patients, 9/16 Parkinson’s disease patients, 14/21 migraine patients, and 18/27 healthy donors. In the DNA from peripheral blood lymphocytes of all studied patients and healthy individuals, MSRV pol sequences have been found. The observed pattern of fiber-fluorescence in situ hybridization (FISH) signals suggests the presence of multiple copies of MSRV pol sequences, most likely tandemly dispersed in the genome. It can be concluded that MSRV pol sequences are endogenous, widespread in lymphocytes DNA, and transcribed into RNA of MS patients as well as of other studied patients and healthy individuals. However, more frequent expression of MSRV sequences detected in lymphocytes RNA (cDNA), as well as their presence in higher frequency in the serum of MS patients, may suggest the involvement of MSRV in the etiopathogenesis on MS.

Lack of association between an intronic polymorphism in the presenilin-1 gene and sporadic late-onset Alzheimer disease in Polish patients.

The apolipoprotein E (APOE) gene has in many studies been identified as a susceptibility factor in Alzheimer’s disease (AD). The APOE association is rather strong, but other not yet identified genetic factors are assumed to be involved in the pathogenesis of AD. Recently an association between an intronic polymorphism in presenilin-1 (PS-1) gene and late-onset AD was claimed. In order to confirm this observation we studied a sample of Polish patients with sporadic AD. However, our results did not confirm the existence of an association between the intronic polymorphism in the PS-1 gene and late-onset AD.

Detection of IgG subclasses in cerebrospinal fluid and sera of patients with multiple sclerosis and its clinical value

DETECTION OF IgG SUBCLASSES IN CEREBROSPINAL FLUID AND SERA OF PATIENTS WITH MULTIPLE SCLEROSIS AND ITS CLINICAL VALUE J. Los), G. Michalowska-Wender, M. Wender Department of Neurology, University School of Medicine, Pozna6, Poland IgG1, IgG2, IgG3, and IgG4 subclasses were detected in cerebrospinai fluid and sera from 32 patients with MS, of whom 23 had relapsing-remitting and 9 chronic progressive course of the disease. Ten patients with diagnosis of neurasthenia, t=asion headache, epilepsy and syncope served as controls. The ELISA method with monoclonal antibodies sl~cific for human IgGl ! clone HP 60691, IgG2 / clone HI) 60141, IgG3 / clone 60471, IgG4 / clone ITP 6023/and double antibody avidin-biotin-peroxidase system has been applied. There was no statistical difference between values of lgG subclasses in MS and control sofa. The CSF levels of IgG1 and IgG3 in MS patients were higher than those of controls, whereas the levels of IgG2 and IgO4 between these two studied groups were not significantly different. The IgO1 and IgG3 indexes were significantly higher in MS patients than in controls, showing that among four IgG subclasses, IgG1 and IgO3 were synthesized in the central nervous system of patients with MS. The elevation of IgG1 and IgG3 indexes in MS patients was found more frequently/in about 90% of patients/than the elevation of IgG index/in only 72% of patients/.