Complement dependent cytotoxic antibody activity against measles virus in multiple sclerosis

Summary The presence of measles cytotoxic (CT) and hemagglutination inhibiton (HI) antibodies in 195 multiple sclerosis (MS) patients and 251 controls was tested. The measles virus Lu carrier cells labeled with ⁵¹Cr were exposed to serum specimens in the presence of complement in order to test the presence of CT antibody. The analysis of complement dependent CT antibodies against measles virus revealed significantly (P<0.01) higher titers in MS patients than in the control group. However, the measles HI test failed to show this difference. Measles CT titers 1:32 among MS patients occured in 54.9% and in 35.5% among the controls. In comparison with this the HI method revealed measles titers 1:128 more often in the control group than in MS cases (27.9 and 17.9%, respectively). The presence of CT antibodies against measles virus in MS proves that these patients have a functional defence mechanism to eliminate virus infected cells. The high measles antibody titer among MS patients could be due to recurrent antigenic stimulation caused by measles virus persistency. Whether this virus persistency plays a role in MS can not be decided on the available data.Supported by Deutsche Forschungsgemeinschaft (Schwerpunkt Ätiologie und Pathogenese der multiplen Sklerose und verwandter Erkrankungen)     

Identification of a novel T cell epitope of human proteolipid protein (residues 40–60) recognized by proliferative and cytolytic CD4 T cells from multiple sclerosis patients

Research into the pathogenesis of multipe sclerosis (MS) has focused on myelin antigens as potential targets of autoimmune attack. Proteolipid protein (PLP), which makes up more than 50% of central nervous system myelin, is a hydrophilic membrane protein with many properties that historically have made it difficult to study. The use of synthetic peptides based on the PLP sequence provides an alternative method for studying the immunological properties of PLP. Using peripheral blood lymphocytes from MS patients, long-term TCL established in the presence of PLP reacted weakly to PLP in proliferation assays; however, these same lines were much more reactive to synthetic peptides of PLP. Thus, we established short-term T cell lines (TCL) from the peripheral blood lymphocytes (PBL) of MS patients in the presence of five separate synthetic PLP peptides. In six out of seven MS patients, proliferative responses were elicited most often to PLP 40–60 compared to four other PLP peptides (PLP 89–106, 103–120, 125–143, and 139–154). Characterization of PLP 40–60-responsive TCL from a single MS patient, MS1, indicated that six out of seven TCL proliferating to the peptide also lysed PLP 40–60 pulsed autologous targets. All cytolytic PLP 40–60 TCL were CD4⁺ and MHC class II restricted and further analysis of MS1 TCL showed that the PLP 40–60 TCL were restricted by DR4 whereas the MBP TCL from MS1 were restricted by DR6. These findings suggest that difficulties in examining the immune response to PLP have been due to the poor response generated in vitro using the whole molecule and that the use of synthetic peptides may represent an alternative approach to the study of PLP. These results also suggest that MS PBL recognize several PLP peptides, with the predominant response to PLP 40–60. Since these cells phenotypically resemble T cells known to mediate experimental autoimmune encephalomyelitis, it is possible that they may play a role in the pathogenesis of MS.     

Role of perforin secretion from CD8+ T-cells in neuronal cytotoxicity in multiple sclerosis

Objectives: Multiple sclerosis (MS) is the most prevalent autoimmune disease of the central nervous system, and is characterized by inflammation and myelin damage. The immune system initiates the autoimmune response, although the mechanisms of neuronal damage have not been elucidated. The purpose of the present study was to investigate autoreactive CD4+ and CD8⁺ T lymphocytes, in conjunction with other inflammatory cells and cytokines in active MS lesions.

Methods: EAE animal models was established by plantar injections of MBP (200 μg per rat). Purified CD4+ or CD8+ T-cells were isolated from heparinized peripheral blood (EAE animals and control animals) via negative selection. To examine effects of presence of autoreactive CD4+ and CD8+ T lymphocytes, we carried out ELISA, Western blot analysis and TUNEL. In addition, we examined the direct effects of various factors on neuronal cell death using MTT assay.

Results: The data revealed that CD8+ T-cells were more toxic to neurons compared to CD4+ T-cells, in both the MBP and EAE conditions. Bax was greater increased when neurons were co-cultured with CD8+ T-cells in the MBP group. There is a significant increase in IL-17 secretion by CD4+ T-cells in both the MBP group and EAE group. Neuronal viability were affected by Perforin (1.5 μg/mL).

Conclusion: The present study extends previous research by demonstrating the role of CD8+ T-cells in MS and supports perforin secretion by CD8+ T-cells as a potential therapeutic factor. Furthermore, we determined that CD4⁺ T-cells can enhance CD8⁺ T-cell neuronal cytotoxicity via induction of intense inflammation.     

CD8 high CD11b low T cells (T suppressor-effectors) in multiple sclerosis cerebrospinal fluid are increased during high dose corticosteroid treatment

Using simultaneous dual direct immunofluorescence the effect of high dose intravenous methylprednisolone on the expression of T lymphocyte differentiation antigens in paired cerebrospinal fluid and peripheral blood samples of nine clinically active patients with multiple sclerosis was studied. Corticosteroid treatment was associated with a clinical improvement in eight out of the nine patients. In cerebrospinal fluid of all patients the treatment was associated with a decrease of CD3+, CD4+ and CD8+ T cells, and of intra-central nervous system IgG synthesis. CD8+ high CD11b+ low suppressor-effector T cells behaved differently in the eight patients who improved with treatment, where they significantly increased, and in the patient without clinical response, where they were almost unchanged. Similar phenotypic changes were found in peripheral blood, and all changes returned towards baseline after treatment. The lower sensitivity to corticosteroids of CD8+ high CD11b+ low T cells could change the balance between immunoregulatory T subsets. In this study the increased availability of a subpopulation mainly composed of T cells with a suppressor-effector function was associated with a clinical response to treatment.     

Frequency analysis of HLA-B7-restricted Epstein-Barr virus-specific cytotoxic T lymphocytes in patients with multiple sclerosis and healthy controls

The Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS), however, the mechanisms by which EBV may be involved in MS are unknown. We here have investigated the frequency of EBV-specific cytotoxic T lymphocytes (CTL) in human leukocyte antigen (HLA)-B7⁺ patients with MS and healthy controls using enzyme-linked immunospot assays and seven previously characterized HLA-B7-restricted immunogenic EBV peptides. Overall, there were no significant differences in the frequency of EBV-specific CTL between both groups. These data do not support the hypothesis that EBV could play a role in MS by inducing quantitatively altered EBV-specific CTL responses. Other pathogenic mechanisms for EBV in MS remain to be elucidated.     

Psychological stress exacerbates primary vaginal herpes simplex virus type 1 (HSV-1) infection by impairing both innate and adaptive immune responses

Chronic psychological stress is generally immunosuppressive and contributes to an increase in herpes simplex virus (HSV) pathogenicity. We have previously shown that mice experiencing stress at the time of intranasal HSV infection have increased levels of infectious virus in their nasal cavity, as compared to control mice that were not subjected to stress. We have extended our studies to determine the effects of stress at another clinically-relevant mucosal site by examining the immune response to and pathogenesis of vaginal HSV infection. Mice experiencing psychological stress during vaginal HSV infection exhibited an increase in both vaginal viral titers and the pathology associated with this HSV infection. We demonstrate that these observations result from the failure of both the innate and HSV-specific adaptive immune responses. At 2 days post-infection, NK cell numbers were significantly decreased in mice experiencing restraint stress. Studies examining the adaptive immune response revealed a decrease in the number of HSV-specific CD8⁺ T cells in not only the vaginal tissue itself but also the draining iliac lymph nodes (ILN). Furthermore, the number of functional cells, in terms of both their degranulation and interferon-γ production, in the ILN of stressed mice was decreased as compared to non-stressed mice. We conclude that psychological stress, through its suppression of both innate and adaptive immune responses, may be an important factor in the ability to control vaginal HSV infection.     

Stress-induced modulation of the primary cellular immune response to herpes simplex virus infection is mediated by both adrenal-dependent and independent mechanisms

A murine model of herpes simplex virus (HSV) infection was ussed to examine the role of the adrenal gland in restraint stress-induced suppression of viral immunity. Adrenal-dependent mechanisms were important for suppressing the generation of HSV-specific cytotoxic T lymphocytes (CTL) but not the associated diminished lymphadenopathy in response to local HSV infection. While exogenous corticosterone administration alone was unable to suppress lymphadenopathy and CTL generation in adrenalectomized mice, an adrenal-independent mechanism induced by restraints stress functioned in synergy with corticosterone to suppress lymphadenopathy and CTL development. These results suggest that both adrenal-dependent and independent mechanisms cotribute to stress-induced modulation of HSV immunity.     

Interictal alterations of cytokines and leukocytes in patients with active epilepsy

Background

Involvement of the innate immune system in the pathogenesis of epilepsies has been suggested but possible interactions between the immune system and human epilepsy remain unclear. We analyzed the interictal immuno-phenotype of leukocyte subsets and proinflammatory cytokine profiles in epileptic patients and correlated them with the epilepsy syndrome.

Methods

101 patients with active focal or generalized epilepsy were prospectively included and compared to 36 healthy controls. Immuno-phenotype of leukocyte subsets and cytokines IL-1β, IL-6 and tnfα were measured in peripheral blood. Multivariate analyses were performed to test group differences.

Results

As compared to controls, the patients showed an elevated percentage of monocytes (18.06 ± 7.08% vs. 12.68 ± 4.55%, p < 0.001), NK cells (14.88 ± 7.08% vs. 11.43 ± 5.41%, p = 0.019) and IL-6 concentration (3.33 ± 3.11 pg/ml vs. 1.5 ± 1.36 pg/ml, p = 0.002). This remained true when focal epilepsies or generalized epilepsies were compared separately to controls but only focal epilepsies showed additionally a decrease in B lymphocyts (8.16 ± 3.76% vs. 11.54 ± 4.2%, p < 0.001). Treatment with lamotrigine was associated with a higher percentage of B lymphocytes and valproate with an increased percentage of CD4⁺ T lymphocytes. Therapy with levetiracetam showed a trend towards decreased CD8⁺ T cell counts. No significant differences were seen between focal and generalized epilepsies and between temporal and extratemporal lobe epilepsies.

Conclusion

Patients with active epilepsy revealed interictal alterations of the immune system which varied among specific syndromes and were influenced by antiepileptic drug treatment.     

Interleukin-17-secreting T cells in neuromyelitis optica and multiple sclerosis during relapse

Growing evidence suggests that interleukin (IL)-17 and IL-17-secreting CD4⁺T (Th17) cells are involved in the pathogenic mechanisms of multiple sclerosis (MS). IL-17-secreting CD8⁺T cells were recently identified as a novel subset of CD8⁺T cells. We aimed to analyze the role of Th17 and IL-17 secreting CD8⁺T cells in the pathogenesis of neuromyelitis optica (NMO) as well as MS. Fourteen patients with NMO, 20 with MS and 16 control participants (CTL) were enrolled between November 2008 and December 2009. The proportion of Th17 cells and IL-17 secreting CD8⁺T cells were counted using flow cytometry, and serum levels of IL-6, IL-17, IL-21, IL-23, and transforming growth factor-beta (TGF-β) were measured by enzyme-linked immunosorbent assay. Patients with NMO had a larger proportion of Th17 cells than patients with MS (3.72% versus [vs.] 2.58%, p = 0.02) and CTL (3.72% vs. 1.36%, p < 0.001). The proportion of Th17 cells in patients with MS was also markedly higher than in the CTL (2.58% vs. 1.36%, p < 0.001). IL-17-secreting CD8⁺T cell counts in NMO patients were markedly higher than in MS patients (1.61% vs. 1.09%, p = 0.036) and CTLs (1.61% vs. 0.58%, p < 0.001). The proportion of IL-17-secreting CD8⁺T cells in MS patients was also higher than in CTLs (1.09% vs. 0.58%, p = 0.002). Serum IL-17 and IL-23 levels were increased in patients with NMO and MS, while serum IL-21 concentration was higher only in NMO patients compared to CTL. We concluded that Th17 cells were highly activated in patients with NMO. IL-17-secreting CD8⁺T cells were increased in patients with NMO and MS during relapse and have an important role in the pathological mechanism of NMO and MS.     

Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura

Immunoregulatory CD4(+)CD25(+) T cells play an important role in the induction and maintenance of peripheral self-tolerance. These professional regulatory cells prevent the activation and proliferation of potentially autoreactive T cells that have escaped thymic deletion. Therefore, CD4(+)CD25(+) T cells are believed to possibly play an important role in pathogenic autoimmune diseases. We measured the count of CD4(+)CD25(+) T cells in 44 patients with idiopathic thrombocytopenic purpura (ITP), and the number of CD4(+)CD25(+) T cells and clinical features were then analyzed. By using a flow cytometric analysis, the number of CD4(+)CD25(+) T cells in the patients with ITP showed a very wide distribution in comparison to healthy volunteers. The number of CD4(+)CD25(+) T cells was significantly lower in the ITP patients in the severe phase, and in patients positive for anti-glycoprotein IIb-IIIa antibody. However, the number of those cells increased in the patients at the complete remission phase, especially after a splenectomy. The Foxp3 mRNA levels of peripheral blood mononuclear cells (PBMC) of ITP patients were higher with an improved platelet count than in those with a low platelet count. In addition, the Foxp3 mRNA levels closely correlated with the number of CD4(+)CD25(+) cells. These mechanisms remain to be fully elucidated, however, the count of CD4(+)CD25(+) T cells is considered to possibly be related to the severity of ITP.     

Cytotoxic CD4+ T cells are correlated with better prognosis in Han Chinese grade II and grade III glioma subjects and are suppressed by PD-1 signaling

Purpose: Malignant gliomas are the most common tumors in the central nervous system with a poor prognosis. Recently, CD4⁺ cytotoxic T cells (CTLs) are being increasingly recognized as possessing antitumor capacity. However, their presence, activity and regulation in glioma have not been investigated in detail. Methods: To examine this, 72 grade II and grade III Han Chinese glioma patients and 30 Han Chinese healthy controls were investigated. Results: We found that compared to healthy controls, glioma patients had significantly upregulated frequencies of circulating CD4⁺ CTLs, identified by the expression of granzyme A (GzmA), granzyme B (GzmB) and/or perforin. The stimulated CD4⁺ CTLs in grade II and grade III glioma patients also had less proliferative ability than those in healthy controls, a feature of suppression that progressed with tumor grade. The frequencies of GzmB-expressing circulating CD4⁺ CTLs were directly associated with prognosis. We hypothesized that the programed death 1 (PD-1)/PD-ligand 1 (L1) interaction possibly contributed to the suppression of CD4⁺ CTLs in grade II and grade III glioma, since an upregulation of PD-1 was observed on CD4⁺ CTLs in glioma compared to those in the healthy individuals. Blockade of the PD-1/PD-L1 interaction with neutralizing antibodies significantly increased the proliferation and granzyme or perforin production by CD4⁺ CTLs in grade II and grade III glioma patients. Conclusions: These data suggest that the CD4⁺ CTLs in grade II and grade III glioma patients contribute to antitumor immunity and could be suppressed by PD-1 signal transduction.     

Increased Fas-mediated cytotoxicity of CD4-positive T cells in patients with human T-lymphotropic virus type I-associated myelopathy

Using a

Full-size image

release assay, we investigated Fas-mediated cytotoxicity of peripheral blood CD4⁺ T cells of patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM) against T98G, a glioblastoma cell line which expresses Fas. Cytotoxic activity of CD4⁺ T cells against T98G was significantly higher in HAM patients than in controls. Moreover, when CD4⁺ T cells of HAM patients were preincubated with a monoclonal antibody to human Fas ligand (FasL), cytotoxic activity against T98G was significantly suppressed. These results suggest that damage to nervous tissues by the Fas/FasL system is involved in the pathogenesis of HAM.     

IL-27 mediates the response to IFN-β therapy in multiple sclerosis patients by inhibiting Th17 cells

Interferon (IFN)-β is a commonly used therapy for relapsing remitting multiple sclerosis (RRMS). However its protective mechanism is still unclear and the failure of many patients to respond has not been explained. We have found that IFN-β suppressed IL-23 and IL-1β production and increased IL-10 production by human dendritic cells (DC) activated with the TLR2 and dectin-1 agonist zymosan. Furthermore, IFN-β impaired the ability of DC to promote IL-17 production by CD4⁺ T cells, but did not affect IFN-γ production. IFN-β induced IL-27 expression by DC, and neutralisation of IL-27 abrogated the suppressive effects of IFN-β on zymosan-induced IL-1 and IL-23 production and the generation of Th17 cells in vitro. Complementary in vivo studies in a mouse model showed that treatment with IFN-β enhanced expression of IL-27, and reduced IL-17 in the CNS and periphery and attenuated the clinical signs of experimental autoimmune encephalomyelitis (EAE). In addition, the significant suppressive effect of IFN-β on the ability of DC to promote Th17 cells was lost in cells from IL-27 receptor deficient mice. Finally, we showed that PBMC from non-responder RRMS patients produced significantly less IL-27 in response to IFN-β than patients who responded to IFN-β therapy. Our findings suggest that IFN-β mediates its therapeutic effects in MS at least in part via the induction of IL-27, and that IL-27 may represent an alternative therapy for MS patients that do not respond to IFN-β.     

Characterization of brain-infiltrating mononuclear cells during infection with mouse hepatitis virus strain JHM

The eradication of infectious virus from the central nervous system (CNS) following infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) is thought to be immune-mediated. Furthermore, a significant decrease of infectious virus coincides with the appearance of prominent inflammatory infiltrates in the brain and spinal cord. In the present study, mononuclear cells infiltrating the brain during JHMV infection were isolated and characterized. While all subsets of immune cells were present, there appeared to be a temporal relationship between the peak incidence of CD8+ T cells (40% of total isolated cells) and reduction of virus at day 7 post-infection. Cells with the natural killer (NK) phenotype (at least 30%) were also present throughout infection. These data suggest that CD8+ T cells and NK cells are prominent among cells which infiltrate the brain during JHM virus infection and may have important roles in reduction of virus within the CNS.     

Evidence for a missed signal to the CD8+ cells in CSF of Multiple Sclerosis patients

Peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte subpopulations, defined by various T-cell specific monoclonal antibodies and flow cytometry, were analysed in 44 relapsing remitting multiple sclerosis (RRMS) patients (including 21 subjects in the acute phase and 23 in the stable phase), 40 chronic-progressive multiple sclerosis (CPMS) patients, and 24 patients with other neurological diseases (OND), in order to verify the presence of any abnormality in the lymphocyte subset pattern. A significant increase in the total number of T-lymphocytes and the CD4+ subpopulation was found in the PB of the MS patients in comparison with the OND group. Moreover, a not statistically significant increase in CD4⁺ cells was observed in the CSF of MS patients. A statistically significant increase was also found in the CD4⁺ Leu 8⁺ (suppressor inducer) cells in the CSF of all of the MS groups. Finally, the CD8⁺ (suppressor/cytotoxic) cell levels, were significantly lower in the CSF of CPMS and stable RMS patients than in the CSF of the OND patients. As a whole, our data suggest that the immunosuppressive deficit that seems to be a constant finding in MS is not due to a decrease in suppressor inducer cell levels, as previously suggested, but may be caused by a missed or altered signal from the suppressor inducer to CD8⁺ suppressor cells.This Work was partially supported by an IRCCS Current Research Grant 1994.     

首发抑郁症患者外周血CD4+CD25+CD127-调节性T细胞的研究

目的 探讨首发抑郁症患者治疗前后外周血中CD4⁺CD25⁺CD127^-占CD4⁺的比例及Treg细胞与抗抑郁治疗的相关性。方法 纳入在大庆市第三医院住院治疗的首发抑郁症患者共20例,均符合《精神障碍诊断与统计手册（第5版）》（DSM-5）关于抑郁障碍的诊断标准,汉密尔顿抑郁量表17项版（HAMD-17）总评分>20分;同期纳入在大庆市第三医院体检中心的健康成人作为对照组,共20例。对抑郁症患者治疗前及治疗12周后分别进行HAMD-17评定。对抑郁症患者治疗前、治疗12周后及健康对照组分别采取其外周血,利用流式细胞术（FCM）测定外周血CD4⁺CD25⁺CD127^-占淋巴细胞的百分比及CD4⁺CD25⁺CD127^-占CD4⁺T细胞的百分比,并作对照分析。结果 在CD4⁺CD25⁺CD127^-/CD4⁺的水平上,抑郁症患者治疗前、治疗后均高于健康对照组,差异均有统计学意义（P均<0.01）;抑郁症患者HAMD-17评分及血清CD4⁺CD25⁺CD127^-/CD4⁺的水平均下降,差异均有统计学意义（P均<0.05）,且抑郁症显效组CD4⁺CD25⁺CD127^-/CD4⁺的变化率与HAMD-17评分减分率呈正相关（r=0.716,P<0.05）。结论 抑郁症患者经SSRIs类药物治疗后,外周血CD4⁺CD25⁺CD127^-/CD4⁺水平的降低预示抗抑郁疗效较好,有效的抗抑郁治疗可能与调节T细胞有一定的相关性。     

Immunogenic dendritic cells primed by social defeat enhance adaptive immunity to influenza A virus

Dendritic cells (DCs) sample their surrounding microenvironment and consequently send immunogenic or regulatory signals to T cells during DC/T cell interactions, shaping the primary adaptive immune response to infection. The microenvironment resulting from repeated social defeat increases DC co-stimulatory molecule expression and primes DCs for enhanced cytokine responses in vitro. In this study, we show that social disruption stress (SDR) results in the generation of immunogenic DCs, capable of conferring enhanced adaptive immunity to influenza A/PR/8/34 infection. Mice infected with influenza A/PR/8/34 virus 24 h after the adoptive transfer of DCs from SDR mice had significantly increased numbers of D^bNP_366-74CD8⁺ T cells, increased IFN-γ and IFN-α mRNA, and decreased influenza M1 mRNA expression in the lung during the peak primary response (9 days post-infection), compared to mice that received DCs from naïve mice. These data demonstrate that repeated social defeat is a significant environmental influence on immunogenic DC activation and function.     

Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis

T cell sensitization to two myelin components, myelin basic protein (MBP) and myelin proteolipid protein (PLP), may be important to the pathogenesis of multiple sclerosis (MS). Using the limiting dilution assay, we demonstrated that the blood of MS patients had an increased frequency of MBP-reactive T cells compared with normal subjects and patients with other neurological diseases (OND) and rheumatoid arthritis. There was no difference in T cell frequency to a synthetic peptide, PLP139-151, or Herpes simplex virus. Within cerebrospinal fluid (CSF), 37% of IL-2/IL-4-reactive T cell isolates from MS patients responded either to MBP or PLP139-151 while only 5% of similar isolates from OND patients responded to these myelin antigens. The mean relative frequency of MBP-reactive T cells within CSF from MS patients was significantly higher than that of OND patients (22 x 10(-5) cells versus 1 x 10(-5) cells) and was similar to that of MBP reactive T cells within the central nervous system of rats with experimental autoimmune encephalomyelitis. These results lend new support to the hypothesis that myelin-reactive T cells mediate disease in MS.     

Soluble CD4 and CD8 in the peripheral blood of patients with multiple sclerosis and HTLV-1-associated myelopathy

We evaluated the presence of soluble (s) CD4 and sCD8, released from activated T cells, in the sera of patients with multiple sclerosis (MS) and human T lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM) using an enzyme-linked immunosorbent assay (ELISA). In addition, peripheral blood T cell subsets in patients with MS and HAM were analyzed by single and two color flow cytometry. The serum level of sCD8 was significantly elevated in MS patients as compared with controls (p less than 0.001). Sera from patients with an exacerbation of acute relapsing MS showed a higher sCD8 level than the patients in remission or controls (p less than 0.01 and p less than 0.001, respectively). The serum levels of both sCD4 and sCD8 were also significantly elevated in patients with HAM (p less than 0.001 and p less than 0.001, respectively). In addition, a significantly increased serum level of soluble interleukin-2 receptor (sIL-2R) was found in patients with HAM as compared with that of controls (p less than 0.001). These observations suggest that CD8 cells may be activated in the peripheral blood of patients with MS and sCD8 may be related to clinical activity, but that both CD4 and CD8 cells may be activated in the peripheral blood of patients with HAM.     

Increased levels of soluble vascular cell adhesion molecule-1 ( VCAM-1) in the cerebrospinal fluid and sera of patients with multiple sclerosis and human T lymphotropic virus type-1-associated myelopathy

We evaluated the relationship between the soluble form of vascular cell adhesion molecule-1 (sVCAM-1) and disease activity in patients with multiple sclerosis (MS) or with human T lymphotropic virus type 1-associated myelopathy (HAM), and measured levels of sVCAM-1 in their cerebrospinal fluid (CSF) and sera. Serum and CSF levels of sVCAM-1 were significantly increased in patients with acute relapsing MS during an exacerbation (P < 0.01 and P < 0.001), as well as in chronic progressive MS (P < 0.05 and P < 0.001), compared with healthy individuals and patients with other neurological diseases, respectively. Patients with acute relapsing MS during an exacerbation also exhibited significantly higher serum and CSF levels of sVCAM-1 vs. patients with acute relapsing MS in remission (P < 0.001). Significantly higher serum levels of sVCAM-1 were observed in patients with HAM vs. either healthy individuals (P < 0.01) or non-HAM carriers (P < 0.01). These results suggest that the determination of sVCAM-1 in the sera and CSF may be useful in monitoring the activity of MS and HAM.