Background: There is currently no international reference preparation for IgG subclass (IgGSc) quantification. This situation has led to calibration differences among assays and a variety of reference interval values with consequential difficulties in comparing results. We therefore evaluated IgGSc concentrations in Certified Reference Material 470 (CRM 470). Methods: Pure, polyclonal IgG1, -2, -3, and -4 were prepared from a large serum pool for use as primary standards. The IgG mass in each preparation was calculated from amino-acid analysis data. IgGSc concentrations were assessed in CRM 470 by nephelometry with modern analytical techniques, using these reference preparations. Subsequently, IgGSc concentrations were measured in 380 healthy individuals (250 males and 130 females), and age-dependent reference intervals were established.

CXCL13 shows high sensitivity and specificity for acute, untreated LNB. This novel marker appears to be helpful in clinically atypical cases and, in particular, in early stages of the disease when the B burgdorferi AI is (still) negative.

MRZR is the most specific laboratory marker of MS reported to date. If present, MRZR substantially increases the likelihood of the diagnosis of MS. Prospective and systematic studies on the diagnostic and prognostic impact of MRZR testing are highly warranted.

Chronic intrathecal immunoglobulin (Ig) production is a hallmark of multiple sclerosis characterized by the presence of oligoclonal IgGs and, in addition, polyspecific recognition of different pathogens such as measles, rubella and herpes zoster virus. While the antigen specificity of the oligoclonal IgGs in multiple sclerosis is largely unknown, the oligoclonal IgGs arising during CNS infectious diseases are reactive against the specific pathogen. Recently, a link between Chlamydia pneumoniae and multiple sclerosis has been claimed. To test the possible role of C. pneumoniae in multiple sclerosis, we analysed (i) whether there is intrathecal IgG production against C. pneumoniae in multiple sclerosis and (ii) if the oligoclonal IgGs in the CSF of multiple sclerosis patients recognize C. pneumoniae. By studying paired serum-CSF samples from 120 subjects (definite multiple sclerosis, 46; probable multiple sclerosis, 12; other inflammatory neurological diseases, 35; other neurological diseases, 27) by enzyme-linked immunosorbent assay, we found that 24% of all patients with definite multiple sclerosis, but only 5% of patients with other inflammatory or non-inflammatory diseases, produced IgGs specific for C. pneumoniae intrathecally (definite multiple sclerosis versus other inflammatory neurological diseases: P = 0.027). The presence of intrathecal IgGs to C. pneumoniae was independent of the duration of disease and relatively stable over time. The major CSF oligoclonal IgG bands from multiple sclerosis patients with an intrathecal Ig production to C. pneumoniae did not react towards purified elementary bodies and reticulate bodies of C. pneumoniae on affinity-mediated immunoblot following isoelectric focusing (IEF-western blots). In contrast, the IgGs in the CSF of control patients with neuroborreliosis strongly reacted with their specific pathogen, Borrelia burgdorferi, by IEF-western blot analysis. Concomitant analysis of the CSF of 23 patients with a nested polymerase chain reaction for C. pneumoniae was negative in all cases. Together, our findings strongly suggest that the immune response to C. pneumoniae is part of a polyspecific intrathecal Ig production, as is commonly observed with other pathogens. This argues against a specific role for C. pneumoniae in multiple sclerosis.

Background: A polyspecific, intrathecal humoral immune response against neurotropic viruses such as measles, rubella and varicella zoster virus (MRZ reaction, MRZR) is present in 80-100% of patients with multiple sclerosis (MS), but has not to date been evaluated in patients with neuromyelitis optica (NMO). Aims: To evaluate whether MRZR distinguishes NMO and MS. Methods: 20 patients with NMO and 42 with MS were included. The intrathecal synthesis of antibodies against measles, rubella and varicella zoster virus was detected by calculation of the respective antibody indices (AI). Results: A positive MRZ reaction, as defined by a combination of at least two positive AIs, was found in 37/ 42 MS, but in only 1/20 NMO patients (p,0.0001).Median AI values differed significantly between the groups (p,0.0005). Conclusions: The polyspecific antiviral humoral immune response characteristic for MS is widely missing in NMO, irrespective of the NMO-IgG status of the patients. Our findings further strengthen the case for NMO being pathologically distinct from MS.Neuromyelitis optica (NMO, Devic syndrome) is a severe inflammatory disorder of the CNS of putative autoimmune aetiology, predominantly affecting the spinal cord and optic nerves. 1Whether NMO is distinct from multiple sclerosis (MS) or rather a variant of MS is currently under discussion.2 3 To further elucidate this question, we compared the antiviral, intrathecal antibody repertoire in MS and NMO. MS is well known to be characterised by a polyspecific, intrathecal B cell response against neurotropic viruses such as measles, rubella and varicella zoster virus (MRZ reaction, MRZR), which is detectable in 80-100% of patients with MS. [4][5][6][7][8][9] In this study, we investigated whether such a reaction is also present in NMO, and whether it might help to distinguish between NMO and MS. ) were detectable in 7/20 patients (35%; 4/7 NMO-IgG positive) during the course of disease. NMO followed a relapsing course in 18 patients and was monophasic in two. Median follow-up was 39 months (range 11-288). Serum and CSF samples were obtained 0-286 months from first myelitis (median 2 months; ,6 months in nine patients; .24 months in four) and 0-282 months from first optic neuritis (median 11 months; ,6 months in nine patients; .24 month in seven). As a control group, MRZR results from 42 consecutive patients with MS (28 with myelitis) from Germany were analysed, including 29 patients with relapsingremitting MS (RRMS), four patients with secondary progressive MS (SPMS) and nine patients with a clinically isolated syndrome suggestive of MS (CIS) at the time of lumbar puncture. Diagnosis of MS was established according to McDonald and colleagues. 12 The sex distribution was 1:3.2 (10 men, 32 women). Median age was 34.5 years (range 18-62). Serum and CSF samples were collected 0-294 months from first relapse (median 13 months; ,6 months in 17 patients; .24 months in 15). All lumbar punctures were performed for diagnostic purposes only. PATIENTS AND METHODSQuantita...

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To determine whether matrix metalloproteinase (MMP)-9 is a potential mediator involved in the frequently detected blood-brain barrier leakage in human immunodeficiency virus (HIV)-infected patients, zymography was used to detect MMP-9 activity in cerebrospinal fluid (CSF) samples of 80 HIV-infected patients and of 10 control patients. CSF MMP-9 activity was detected in 40% of HIV-infected patients (but not in controls) and was significantly more frequent in HIV-infected patients than in those without neurologic deficits (50% vs. 13.6%). The frequency of CSF MMP-9 activity did not significantly differ between neurologically symptomatic HIV-infected patients with or without opportunistic central nervous system disease (51.6% vs. 48.1%). Additionally, the presence of CSF MMP-9 activity in HIV-infected patients was associated with an increased CSF white blood cell count and an elevated CSF-to-serum albumin ratio, suggesting that it may play a role in blood-brain/CSF barrier leakage in HIV-infected patients.