Immune-related Markers Research Articles

ERYTHROCYTE SEDIMENTATION RATE IN ALZHEIMER'S DEMENTIA

To the Editor: Although the brain has often been viewed as immunologically privileged, it does possess the capacity to produce almost all immune system mediators. Hallmark lesions of Alzheimer's dementia (AD) have been characterized by stage-dependent amyloid deposits detected in association with immunoreactive microglia cells.1 AD is associated with an increased expression of several immune-related markers in the brain, including MHC class II antigens, complement factors, and acute-phase proteins.2 Peripheral tissues of AD patients also show evidence of an inflammatory response. Investigators report elevated levels of tissue necrosis factor in AD sera compared with sera of nondemented controls.3 Moreover, AD patients with severe dementia frequently demonstrate elevated circulating immune complexes not seen in patients with mild or moderate disease.4 Epidemiological studies of arthritis patients on long-term anti-inflammatory drug therapy have noted the under-representation of neurodegenerative dementia in this population.2 Twin studies of 50 pairs of older adults (52% were monozygous) with AD found the onset of AD was inversely associated with prior use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and adrenocorticotropic hormone (ACTH). The association was strongest with the combined use of steroids/ACTH or NSAIDs.5 The erythrocyte sedimentation rate (ESR) is the measurement of erythrocyte settling rate in anticoagulated blood under standard conditions. It has a relatively high sensitivity and low specificity.6 Although the ESR has extensive use as a nonspecific marker of inflammatory conditions, we could find no previous reports of its use in Alzheimer's or other dementias. Fifty subjects and seventeen controls were selected from the Palo Alto Veteran Affairs Medical Center/Stanford Alzheimer's Center database. The subjects met the diagnosis of probable Alzheimer's dementia based upon National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. The 17 individuals with no history or diagnosis of dementia comprised a control group. Their diagnoses included: no cognitive impairment, age-associated memory impairment, or cognitive impairment not meeting criteria for dementia. Any history for conditions that might effect ESR, such as active or chronic peripheral infections, arthritis, autoimmune disorders, a prolonged history of using cognition-enhancing medications or anti-inflammatory medications, abnormal immune indices, or a history of head trauma excluded subjects. Thirty-three subjects and 11 controls were excluded from the study for illness, disease, or dependence on antiinflammatory medications. The results indicate that ESR level was not significantly elevated in the total demented group compared with the nondemented control group F(1,63) = 2.32, P = .14 (see Table 1). There was an intergender difference, with female ESR significantly higher than male ESR F(1,63) = 6.017, P = .01. There was also an age-ESR difference revealing significantly higher ESR values with increasing age F(1,62) = 4.325, P = .04. The much younger control group may have contributed to these findings. The goal of this study was to evaluate the efficacy of the ESR as a nonspecific indication of inflammatory process in Alzheimer's disease. Although there appeared to be a trend towards higher ESR values in demented subjects compared with nondemented controls (Figure 1) we did not find a significant difference between the two groups. Currently, the use of the ESR as a screening test for neuro-degenerative disease is not supported by our findings or the literature. If immune mediated processes are closely linked with neuronal breakdown, having a reliable means to identify these changes seems of consequence. Future studies are needed to follow the longitudinal course of ESR values with serial cognitive testing to determine if a significant relationship exists. The elucidation of a sequential neurodegeneration pattern would provide information useful to accessible clinical staging of AD.

Human fibroblasts in idiopathic retroperitoneal fibrosis express HLA-DR antigens

Idiopathic retroperitoneal fibrosis (IRF) is a rare human disease characterized by non-neoplastic fibroblastic proliferation associated with chronic inflammatory cells; its pathogenesis is obscure. We undertook an immunohistochemical study for the expression of HLA-DR antigens and other immune-related markers by retroperitoneal proliferating fibroblasts and inflammatory cells from 2 IRF patients. Patterns of immunoreactivity were compared with those expressed by human nodular fasciitis (NF) and granulation tissue. In IRF, most fibroblasts immunostained strongly for HLA-DR antigens, whereas fibroblasts in NF and granulation tissue did, not immunostain at all. The fibroblasts did not immunostain for interleukin 2 receptor, C3b receptor, CD-4, CD-8, or Leu-M1 in any of the tissue studied. Most macrophages and lymphocytes in IRF and NF immunostained Strangly for HLA-DR antigens. In IRF, the CD-4 and CD-8 immunostained T-lymphocytes appeared equally distributed. The expression of HLA-DR antigens by fibroblasts in IRF indicates that this rare disease may indeed be an immune-associated hypersensitivity disorder.