Load In Cerebrospinal Fluid Research Articles

Immune response in progressive multifocal leukoencephalopathy: an overview.

Progressive multifocal leukoencephalopathy (PML) is a disease usually occurring in immunosuppressed patients. By far the most common underlying immunosuppressive illness is the acquired immune deficiency syndrome, accounting for about 85% of PML cases currently seen in clinical practice. PML may occur in patients with deficits in the humoral and/or cellular immune response such as lymphoproliferative diseases, myeloproliferative diseases, carcinomatous diseases and acquired immunodeficiency due to autoimmune diseases and immunosuppressive therapy. The humoral immune response in PML is indicative of a persistent, reactivated infection with a prominent immunoglobulin (lgG) G synthesis to virus protein 1 (VP1). An lgM synthesis in serum is rarely found. In about 76% of PML cases, an intrathecal humoral immune response to recombinant VP1 can be found as compared to only 3.2% in healthy controls. The detection of intrathecally synthesized lgG antibodies to VP1 can be used as an additional diagnostic test for the diagnosis of PML. The magnitude of the intrathecal humoral immune response appears to rise over time and may be associated with a decrease of viral load in cerebrospinal fluid (CSF) and possibly the central nervous system (CNS). Compared to healthy controls, proliferation of peripheral blood mononuclear cells (PBMC) is reduced in PML patients. Immunological studies suggest a general impairment of the Th1-type T-helper cell function of cell-mediated immunity. Furthermore, the appearance of JCV-specific cytotoxic T-lymphocytes appears to be associated with a favorable clinical outcome.

The effect of potent antiretroviral therapy and JC virus load in cerebrospinal fluid on clinical outcome of patients with AIDS-associated progressive multifocal leukoencephalopathy.

A multicenter analysis of 57 consecutive human immunodeficiency virus-positive patients with progressive multifocal leukoencephalopathy (PML) was performed, to identify correlates of longer survival. JC virus (JCV) DNA was quantified in the cerebrospinal fluid (CSF) by polymerase chain reaction. Two months after therapy, 4% of the patients without highly active antiretroviral therapy (HAART) and 26% with HAART showed neurologic improvement or stability (P=.03), and 8% and 57%, respectively, reached undetectable JCV DNA levels in the CSF (P=.04). One-year probability of survival was.04 without HAART and.46 with HAART. HAART and lack of neurologic progression 2 months after diagnosis were independently associated with longer survival. Among HAART-treated patients, a baseline JCV DNA <4.7 log, and reaching undetectable levels after therapy predicted longer survival. Survival of AIDS-related PML is improved by HAART when JCV replication is controlled.

AIDS myelopathy is not associated with elevated HIV viral load in cerebrospinal fluid.

The pathogenesis of AIDS-associated myelopathy is unknown. Elevated HIV-1 viral load in CSF has been associated with cognitive impairment. The authors investigated if a similar association exists in patients with myelopathy. The authors evaluated levels of HIV-1 RNA in the CSF of 16 individuals with AIDS myelopathy and in 16 nonmyelopathic HIV-infected control subjects. There was no correlation between levels of HIV-1 RNA and the presence or severity of myelopathy.

High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis.

AIDS dementia and encephalitis are complications of AIDS occurring most frequently in patients who are immunosuppressed. The simian immunodeficiency virus (SIV) model used in this study was designed to reproducibly induce AIDS in macaques in order to examine the effects of a neurovirulent virus in this context. Pigtailed macaques (Macaca nemestrina) were coinoculated with an immunosuppressive virus (SIV/DeltaB670) and a neurovirulent molecularly cloned virus (SIV/17E-Fr), and more than 90% of the animals developed moderate to severe encephalitis within 6 months of inoculation. Viral load in plasma and cerebrospinal fluid (CSF) was examined longitudinally to onset of AIDS, and viral load was measured in brain tissue at necropsy to examine the relationship of systemic and central nervous system (CNS) viral replication to the development of encephalitis. In all animals, plasma viral load peaked at 10 to 14 days postinfection and remained high throughout infection with no correlation found between plasma viremia and SIV encephalitis. In contrast, persistent high levels of CSF viral RNA after the acute phase of infection correlated with the development of encephalitis. Although high levels of viral RNA were found in the CSF of all macaques (six of six) during the acute phase, this high level was maintained only in macaques developing SIV encephalitis (five of six). Furthermore, the level of both viral RNA and antigen in the brain correlated with the severity of the CNS lesions. The single animal in this group that did not have CNS lesions had no detectable viral RNA in any of the regions of the brain. The results substantiate the use of CSF viral load measurements in the postacute phase of SIV infection as a marker for encephalitis and CNS viral replication.

Pretreatment with granulocyte colony-stimulating factor attenuates the inflammatory response but not the bacterial load in cerebrospinal fluid during experimental pneumococcal meningitis in rabbits.

A possible immunomodulatory role of granulocyte colony-stimulating factor (G-CSF) was investigated in an experimental pneumococcal meningitis model in rabbits. Animals were pretreated with G-CSF (10 micrograms/kg subcutaneously twice a day) starting 48 h before in vivo and ex vivo experiments, causing a five- to six-fold increase in the peripheral leukocyte level. Meningitis was induced by intracisternal inoculation of approximately 4 x 10(5) CFU of Streptococcus pneumoniae type 3. Neutrophil pleocytosis and interleukin-8 (IL-8) levels were significantly attenuated in G-CSF-pretreated animals compared to untreated animals (P < 0.05). Furthermore, G-CSF pretreatment significantly delayed alterations in cerebrospinal fluid (CSF) tumor necrosis factor alpha and IL-1beta levels, as well as protein and glucose levels (P < 0.05). No difference in CSF bacterial concentrations was found, whereas the blood bacterial concentration was significantly decreased in G-CSF-pretreated animals (P < 0.05). Ex vivo chemotaxis of neutrophils isolated from G-CSF-pretreated animals was significantly decreased compared to that of neutrophils from untreated animals (P < 0.05). In conclusion, G-CSF pretreatment attenuates meningeal inflammation and enhances systemic bacterial killing. Further preclinical studies are required to investigate whether this may affect the clinical course of meningitis and thus whether G-CSF treatment may have a beneficial role in pneumococcal meningitis.

Recent Developments in Viral Load Measurements in Human Herpesviruses

Recent developments in molecular biology have allowed precise quantitative analysis of herpesvirus DNA in many biological fluids. Th is paper reviews the clinical utility of performing quantitative polymerase chain reaction testing for herpesviruses. In particular, the assessment of the cytomegalovirus (CMV) DNA load in blood with regard to the development of CMV disease in immunocompromised patients is discussed in greater detail. Relevant information exists to support measuring the CMV burden in the blood of AIDS and transplant patients for diagnostic and treatment monitoring purposes, and, to a lesser extent, to envision the monitoring of the circulating Epstein‐Barr virus load for the prevention of pose‐transplant lymphoproliferative disorders. On the ocher hand, there are controversial data on the clinical utility of measuring the herpes simplex virus (HSV) load in cerebrospinal fluid of patients with HSV encephalitis and on the relationship between the human herpesvirus 8 DNA load in diverse biological fluids and the presence of Kaposi′s sarcoma. There is a paucity of information about the clinical impact of quantifying the other human herpesviruses (varicella‐zoster virus, and human herpesviruses 6 and 7).

Neurological disorders during HIV-1 infection correlate with viral load in cerebrospinal fluid but not with virus phenotype.

To verify the compartmentalization of HIV-1 within the central nervous system (CNS) and to define whether viral phenotype of HIV-1 isolates from cerebrospinal fluid (CSF) samples and CSF viral load correlate with the presence and type of neurological disorders. A total of 33 HIV-1-infected patients with and without neurological disorders were included in the study. HIV-1 isolation from paired CSF and peripheral blood mononuclear cell (PBMC) samples was attempted by a standard cocultivation technique; the biological phenotype of HIV-1 isolates was assessed by the MT-2 cell assay. CSF and plasma HIV-RNA levels were measured by a quantitative reverse transcripase-polymerase chain reaction. The rate of HIV-1 isolation from CSF and PBMC was 66% (22 isolates) and 85% (28 isolates), respectively. Seventeen out of 22 (77%) CSF HIV-1 isolates were characterized as non-syncytium-inducing, and 15 out of 28 (68%) isolates from PBMC were typed as syncytium-inducing (SI). The presence of SI isolates in CSF was limited to patients with HIV-1-, cytomegalovirus- or JC virus-related disorders and was often associated with high levels of HIV-1 RNA in the CSF. Our results demonstrate a correlation between high levels of HIV RNA in CSF and the presence of neurological disorders thus indicating a possible role for HIV-1 RNA in the CSF as a biological marker of neurological disease. The finding of viruses with a different phenotype in paired CSF and PBMC indicates that HIV-1 may evolve differently in the brain and in the blood. This suggests compartmentalization of HIV-1 within the CNS.