The Role Of Non-Conventional MR Techniques To Study Multiple Sclerosis
Rovaris M, Comi G, Filippi M
J Neurol Sci 2001 May 1;186 Suppl 1:S3-9
Scientific Institute and Univ of Milan, Ospedale San Raffaele, NeuroImaging Research Unit, Dept of NeuroScience, via Olgettina 60, 20132, Milan, Italy
PMID# 11334984; UI# 21233434
Conventional Magnetic Resonance Imaging (MRI) lacks pathological specificity to the heterogeneous substrates of Multiple Sclerosis (MS) lesions.
And is not able to detect subtle, disease-related changes in the Normal-Appearing White Matter (NAWM).
As a consequence, the correlation between MRI findings and the long-term evolution of MS is moderate at best.
To overcome the limitations of conventional MRI, new quantitative Magnetic Resonance (MR) techniques, such as cell-specific imaging, Magnetization Transfer Imaging (MTI), proton Magnetic Resonance Spectroscopy (MRS), Diffusion-Weighted Imaging (DWI) and Functional MRI (fMRI) have all been recently applied to the study of MS.
These techniques should provide more accurate and pathologically specific estimates of the MS lesion burden than conventional MR and should improve our understanding of the mechanisms leading to MS-related irreversible disability.
Epidemiology Of AutoImmune Reactions Induced By Vaccination
Chen RT, Pless R, Destefano F
J AutoImmun 2001 May;16(3):309-18
National Immunization Program, Centers for Disease Control and Prevention, Vaccine Safety and Development Activity, Atlanta, GA, 30333, USA
PMID# 11334497; UI# 21232959
In order for vaccinations to 'work', the Immune System must be stimulated. The concern that immunizations may lead to the development of AutoImmune Disease (AID) has been questioned.
Since AID occur in the absence of immunizations, it is unlikely that immunizations are a major cause of AID.
Epidemiological studies are needed, however, to assess whether immunizations may increase the risk in some susceptible individuals. This paper discusses the evidence for and against vaccination as a risk factor for AID.
Evidence for immunizations leading to AID come from several sources including animal studies, single and multiple case reports, and Ecologic association.
However more rigorous investigation has failed to confirm most of the allegations.
Unfortunately the question remains difficult to address because for most AIDs, there is limited knowledge of the Etiology, background incidence and other risk factors for their development.
This information is necessary, in the absence of experimental evidence derived from controlled studies, for any sort of adequate causality assessment using the limited data that are available.
Several illustrative examples are discussed to highlight what is known and what remains to be explored, and the type of Epidemiological evidence that would be required to better address the issues.
Examples include the possible association of immunization and Multiple Sclerosis (and other DeMyelinating Diseases), type 1 Diabetes mellitus, Guillain-Barre Syndrome, Idiopathic Thrombocytopenic Purpura, and Rheumatoid Arthritis.
Copyright 2001 Academic Press.
Hepatitis C And D, RetroViruses And AutoImmune Manifestations
Obermayer-Straub P, Manns MP
J AutoImmun 2001 May;16(3):275-85
Medical School of Hanover, Dept of Gastroenterology and Hepatology, Hanover, Germany
PMID# 11334493; UI# 21232955
Chronic infections with Hepatitis C Virus (HCV) are associated with various AutoImmune manifestations, i.e mixed Cryoglobulinemia, MembranoProliferative Glomerulonephritis, AutoImmune Thyroid Diseases, Sporadic Porphyria Cutanea Tarda and B-Cell Lymphoma.
Since exacerbation of Hepatitis occurs in 5-10% of HCV patients receiving Interferon-alpha treatment and may be successfully treated by ImmunoSuppression afterwards, Hepatitis C was also suspected to be associated with AutoImmune Hepatitis.
LKM3 AutoAntiBodies in chronic Hepatitis D Virus (HDV) infection and Epitope recognition are discussed. Lately, endogenous and exogenous RetroViruses have been investigated for the induction of AutoImmune Diseases.
Human A type RetroViral particles (HIAP), reverse transcriptase activity and Anti-HIAP AutoAntiBodies were detected in patients with Sjogren's Syndrome.
Anti-HIAP and anti-HIV p24 AutoAntiBodies are seen in Systemic Lupus Erythematosus, Primary Biliary Cirrhosis and Multiple Sclerosis.
Multiple Sclerosis was even associated with a new human RetroVirus called Multiple Sclerosis associated RetroVirus (MSRV).
In Diabetes long terminal repeats (LTR) were detected in the HLA DQB1 locus, which was shown to associate with an increased risk of Diabetes.
A second RetroVirus called IDDMK(1,2)22 was reported to code for a SuperAntigen, which was implicated as a potential cause of Diabetes. This hypothesis, however, was challenged repeatedly.
Until now it is unknown whether endogenous RetroViruses are aetiological agents of AutoImmune Diseases or an Epiphenomenon, induced by coinfecting Viruses (e.g. Herpes Viruses) and inflammatory processes.
Copyright 2001 Academic Press.
Molecular Mimicry And Antigen-Specific T-Cell Responses In Multiple Sclerosis And Chronic CNS Lyme Disease
Martin R, Gran B, Zhao Y, Markovic-Plese S, Bielekova B, Marques A, Sung MH, Hemmer B, Simon R, McFarland HF, Pinilla C
J AutoImmun 2001 May;16(3):187-92
NeuroImmunology Branch, NINDS, NIH Building, 10 Room 5B-16, 10 Center DR MSC 1400, Bethesda, MD, 20892-1400, USA
PMID# 11334482; UI# 21232944
The concept of molecular mimicry provides and elegant framework as to how cross-reactivity between Antigens from a foreign agent with self proteins may trigger AutoImmune Diseases.
While it was previously thought that sequence and structural homology between foreign and self proteins or the sharing of T-Cell Receptor (TCR) and MHC-binding motifs are required for molecular mimicry to occur.
We have shown that even completely unrelated Peptide sequences may lead to cross-recognition by T-Cells.
The use of synthetic combinatorial peptide libraries in the positional scanning format (PS-SCL) together with novel biometric prediction approaches has allowed us to describe the recognition profiles of individual AutoReactive T-Cell Clones (TCC) with unprecedented accuracy.
Through studies of Myelin-specific TCC as well as clones from the Nervous System of patients suffering from chronic Central Nervous (CNS) Lyme Disease it has become clear that at least some T-Cells are more degenerate than previously anticipated.
These data will not only help us to redefine what constitutes specific T-Cell recognition, but also allow us to study in more detail the biological role of Molecular Mimicry.
A recent clinical trial with an Altered Peptide Ligand (APL) of one of the candidate Myelin Basic Protein (MBP) Epitopes in MS (Amino Acids 83-99) has shown that such a modified MBP Peptide may not only have therapeutic efficacy, but also bears the potential to exacerbate disease.
Thus, we provide firm evidence that the basic principles of cross-recognition and their PathoGenetic significance are relevant in MS.
Copyright 2001 Academic Press
Zeine R, Cammer W, Barbarese E, Liu CC, Raine CS
J NeuroSci Res 2001 May 15;64(4):380-91
Albert Einstein College of Medicine, Dept of Pathology (Neuropathology), Bronx, New York
PMID# 11340645; UI# 21238380
The mechanism by which Oligodendrocytes are depleted from active lesions in Multiple Sclerosis (MS) is not clear but many reports implicate a CytoLytic process.
The most applied animal model for MS, chronic relapsing Experimental AutoImmune EncephaloMyelitis (EAE), has been established in inbred strains of mice, especially SJL and PL.
Studies on Oligodendrocytes from these strains in vitro have been hampered to date by an inability to grow these cells from mouse CNS tissue.
We report here a successful method to culture SJL mouse Oligodendrocytes and have analyzed lysis (burst) of these cells in vitro mediated by the pore-forming protein, Perforin, a candidate effector molecule in inflammatory DeMyelination.
Cultures were exposed to murine Perforin, 36-72 hemolytic U, for up to 2.5 hr and examined using the Oligodendrocyte phenotypic markers O4, GalactoCerebroside and Myelin Basic Protein (MBP), in addition to a membrane dye (DiI) and a marker of Necrosis, Propidium Iodide, (PI).
Cultures were imaged chronologically by phase contrast, ImmunoFluorescence, digital, light and electron microscopy.
Findings showed that the majority of Oligodendrocytes were killed within 60-90 min via pore expansion and ultimately, membrane disruption.
The structural features of the cellular damage comprised:
- Swelling of the Cell Body
- Fenestration and fragmentation of membranes and processes
- Cytoplasmic vacuolation
- Breakdown of the nuclear envelope
Astrocytes in the same system were relatively resistant to cell lysis.
The above patterns of Oligodendrocyte damage in SJL Oligodendrocytes were reminiscent of patterns in the MS lesion, leaving us to conclude that Perforin may play an important role in the human disease.
Copyright 2001 Wiley-Liss, Inc.