Serum and CSF soluble CD26 and CD30 concentrations in healthy pediatric surgical outpatients.

Activated T-helper type 1 (Th1) lymphocytes induce a cellular type immune response, and Th2 lymphocytes, a humoral or antibody-mediated type immune response. Soluble CD26 (sCD26) and soluble CD30 (sCD30) are regarded as markers of Th1 and Th2 lymphocyte activation, respectively. Serum from 112 generally healthy pediatric surgical patients and cerebrospinal fluid (CSF) from 39, aged 1-17 years were measured for sCD26 and sCD30 using an enzyme-linked immunosorbent assay method. The detection limit for sCD26 was 6.8 ng/ml and for sCD30, 1.9 IU/ml. For serum sCD26 and sCD30, 2.5% and 97.5% percentiles constituted the reference limits, and the 95% credible intervals for the percentiles were calculated using regression models with a Bayesian approach. A significant between-gender difference was observed (P = 0.015) in serum sCD26 concentration, of which the lower limits ranged between 273 and 716 ng/ml for girls and 235 and 797 ng/ml for boys. The upper limits ranged between 1456 and 1898 ng/ml for girls and between 1419 and 1981 ng/ml for boys. Moreover, the concentrations of sCD26 increased in infants and children up to 10 years in girls and 12 years in boys. After this however, the values decreased. The serum sCD30 concentration was highest among the youngest infants aged 1 year (80-193 IU/ml), after which a consistent age-related decrease was found. The lowest values were found at the age of 17 years (10-89 IU/ml). A significant between-gender difference in sCD30 concentration was observed (P = 0.019). sCD26 and sCD30 concentrations were low in the CSF samples analyzed: 13.3 ng/ml (median); range 8.3-51.5 ng/ml and 7.6 IU/ml; 2.1-18.5 IU/ml, respectively. Reference limits for serum sCD26 in children aged 1-17 years were established as being 235-1800 ng/ml in toddlers and 400-1800 ng/ml in female adolescents and 700-2000 ng/ml in male adolescents. For sCD30; reference limits of 80-190 IU/ml were established in the youngest age group and 10-90 IU/ml in adolescents.

Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis.

Lyme neuroborreliosis is a complex disease with different clinical outcomes and where immunopathological mechanisms are probably involved. In this study, sera and cerebrospinal fluid (CSF) from 21 neuroborreliosis patients and 26 control patients were analyzed for the Th1-inducing cytokines, interleukin (IL)-12 and IL-18, and the Th2 associated, soluble CD30 (sCD30) by ELISA. The results showed an increased number of neuroborreliosis patients expressing IL-12 (p<0.05) and IL-18 (p<0.05) in the CSF when compared with the controls, but no indication of increased levels in the sera. Nor were there any differences regarding levels of sCD30 in the sera or the CSF, indicating a local Th1-generating milieu in the target organ of neuroborreliosis.

[Diffuse large B-cell lymphoma showing CNS invasion by CD30-positive multinuclear giant cells mimicking the clinical features of progressive multifocal leukoencephalopathy].

We report a 55-year-old woman with diffuse large B-cell lymphoma showing central nervous system (CNS) infiltration by CD30-positive lymphoma cells. The patient was admitted with pleural effusion, ascites and a large mass in the abdominal cavity. Southern blot analysis of DNA extracted from the ascites revealed IgJH rearrangement, and therefore she was initially diagnosed as B-cell neoplasia. She received combined chemotherapy (DICE and CHOP regimens), and achieved a transient clinical response. Three months later, she developed various neurological abnormalities, and brain magnetic resonance imaging revealed diffuse infiltration of the cerebral white matter. We considered the possibility of CNS involvement by the lymphoma or progressive multifocal leukoencephalopathy (PML), and began a course of anti-virus therapy and radiation therapy. Because multiple lumbar punctures demonstrated large multinuclear lymphoma cells in the cerebrospinal fluid, a diagnosis of metastatic CNS lymphoma was made. Immunohistochemistry revealed that these lymphoma cells were reactive with anti-CD30 antibody. Although the radiation therapy was temporarily effective against the CNS involvement, the patient died of systemic invasion of the lymphoma cells. The final diagnosis was diffuse large B-cell lymphoma on the basis of pathologic findings, immunohistochemistry, and Southern blot analysis using a mesenteric lymph node obtained at autopsy. Cytospin preparations and immunohistochemistry of specimens obtained from frequent lumbar punctures were useful for differentiating CNS lymphoma from PML.

Evaluation of the clinical utility of cerebrospinal fluid (CSF) indices of inflammatory markers in multiple sclerosis.

OBJECTIVES: Accumulating evidence indicates significant heterogeneity in MS and soluble (s) adhesion molecules are postulated as markers of disease activity. We sought to evaluate intrathecal production of these and other molecules across the clinical spectrum of MS. METHODS: CSF indices of IgG, sICAM-1, sVCAM-1, sE-selectin and sCD30 were calculated in 17 primary progressive (PPMS) patients, 15 secondary progressive patients (SPMS), 28 relapsing-remitting patients in relapse (RRMSR) and 14 RRMS patients in remission (RRMSNR) using commercially available ELISA kits. Patients had not received any immunomodulating therapy within the previous 6 months. MS patients were compared with 44 patients with non-inflammatory neurological diseases (NINDs). RESULTS: The most sensitive CSF index at a 90% level of specificity was for IgG which had 93% sensitivity in RRMSR and 92% sensitivity in RRMSNR. Corresponding sensitivity in PPMS and SPMS was 71% and 73% respectively. None of the other indices had sensitivity >50% apart from sVCAM-1 (64% in RRMSR and 52% RRMSNR) and sCD30 (53% in PPMS). CONCLUSIONS: Unsurprisingly the strongest association in MS was with the intrathecal production of IgG. Similar results in PPMS and SPMS may reflect comparable rates of progression in these 2 groups. Of the other molecules only intrathecal sVCAM-1 production is significantly associated with MS and only in relapsing-remitting disease.

Elevated serum and CSF levels of soluble CD30 during clinical remission in multiple sclerosis.

OBJECTIVE: To ascertain the presence of the Th2 response in MS patients by evaluating the level of soluble (s) CD30 across the clinical spectrum of MS and during relapse and remission. BACKGROUND: MS is considered a T-cell-mediated disorder with the immune attack dominated by a Thl cytokine response. Elevated levels of sCD30 have been associated with CD4+ cells that secrete Th2-type cytokines. METHODS: Levels of sCD30 were determined in the serum and CSF of patients with primary progressive MS, secondary progressive MS, relapsing-remitting MS (RRMS), both in relapse and remission, and in patients with other inflammatory neurologic disease (IND) and noninflammatory neurologic disease (NIND). None of the patients were on immunomodulatory treatment. RESULTS: Higher serum levels of sCD30 were detected in all MS subgroups and IND patients compared with NIND patients. RRMS patients in remission had significantly higher levels than those in relapse (median, 45.7 U/mL versus 18.3 U/mL; p = 0.04). Significantly higher CSF levels were also found in all groups, except those with RRMS in relapse compared with NIND patients. Again, RRMS patients in remission had higher CSF sCD30 levels compared with those in relapse (median, 4.0 U/mL versus 3.0 U/mL; p = 0.08). CONCLUSIONS: Serum and CSF levels of sCD30 are increased in MS, particularly during remission. The results provide additional evidence for the presence of a Th2 response and indicate that sCD30 may be of value as a marker of lesion resolution.