We derived a total of 146 T lymphocyte lines specific for human myelin basic protein (MBP) from the peripheral blood of 20 MS patients and from a control group of 12 healthy donors, and determined the reactivities of T cell lines by [3H]thymidine incorporation on exposure to MBP and MBP peptides 1-44, 45-89, and 90-170. We defined HLA restriction of the T lines by using monoclonal antibodies against monomorphic determinants on human HLA-DR, HLA-DQ, and HLA-DP molecules. MBP-specific T cell lines could be isolated with a comparable efficiency from MS patients and healthy individuals. In both groups, MBP-specific T lymphocytes recognized at least 4 different epitopes in the MBP molecule, and specificities showed comparable patterns for different MBP peptides. MBP-specific T cell lines derived from MS patients and controls were restricted by DR products of the human major histocompatibility class II locus. Notable phenotypic differences of T cell lines existed between the 2 groups. Lines isolated from MS patients expressed predominantly the CD3+ CD4+ CD8- phenotype, while some control lines were composed of up to 87% CD3+CD4+CD8+ T lymphocytes. These findings illustrate the presence of MBP-specific T cells in MS patients and controls that are similarly sensitized to MBP and restricted by HLA-DR products.
A panel of 20 human myelin basic protein (hMBP)-specific T-lymphocyte lines was generated from the peripheral blood of eight multiple sclerosis (MS) patients and two healthy donors, most of them expressing the HLA-DR2 haplotype, which is associated with an increased susceptibility to MS. Using HLA-DR gene-transfected mouse L-cell lines as antigen-presenting cells, we established that of the 20 hMBPspecific T-lymphocyte lines, 7 were restricted by the DR2a gene products of the DR2Dw2 haplotype. Four T-cell lines recognized hMBP in the context of the DR2b products of the DR2Dw2 haplotype. DR2b-restricted T-cell responses were demonstrable only in T-cell lines derived from MS patients. The hMBP epitopes presented by the DR2a heterodimer were mapped to peptides covering amino acid residues 144, 76-91, 131-145, or 139-153 and to a region spanning the thrombincleaved bond at Argl3 Alat3I. DR2b-restricted T-cell lines recognized epitopes within amino acids 80-99 and 148-162. Peptide 139-153 was also presented in the context of HLA-DR1 molecules. Our data show that (i) in MS patients both the DR2a and DR2b products of the DR2IDw2 haplotype function as restriction elements for the myelin autoantigen hMBP, (ii) the DR2a molecule presents at least five different epitopes to hMBP-specific T lymphocytes, and (iu) anti-hMBP T-cell lines derived from individual donors can differ in their antigen fmne specificity as well as in their HLA restriction.
BackgroundThe importance of incorporating quality-of-life (QoL) assessments into medical practice is growing as health care practice shifts from a “disease-based” to a “patient-centered” model. The prevalence of age-related macular degeneration (AMD) is increasing in today’s aging population. The purpose of this paper is: (1) to discuss, by reviewing the current literature, the impact of AMD on patients’ QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2) to make a recommendation for incorporating QoL into clinical practice.MethodsWe conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected.ResultsAMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA). QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients’ valued activities, which are not captured by a single, numerical VA score.ConclusionThe literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease-specific instruments for measuring QoL, such as the NEI VFQ-25, have shown a significant correlation of QoL decrement with measures of disease severity, as well as significant QoL improvement with treatment. The NEI VFQ-25 and other validated instruments provide a wide-ranging assessment of vision-related functioning that is important to patients and complementary to VA measurement. We strongly recommend the incorporation of QoL assessment into routine clinical practice.
PDT with verteporfin for PCV appears to improve or maintain VA for the first posttreatment year. Approximately 70% of PCV cases showed improved ophthalmoscopic findings. However, as polypoidal lesions recur after PDT in some cases, further study is needed to confirm the long-term efficacy of PDT for PCV.
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