Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mix- ture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI=4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS

Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin

BACKGROUND: An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. METHODOLOGY/PRINCIPAL FINDINGS: Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63. CONCLUSIONS/SIGNIFICANCE: While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes

Kappa free light chains is a valid tool in the diagnostics of MS : A large multicenter study

To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche

Current status of scrapie. CAB review for Perspectives in Agriculture

Despite being controlled in many developed countries, scrapie remains endemic in many parts of the world. Economic losses result from mortality and culling of small ruminants and from market restrictions. Moreover, it is difficult to develop all-inclusive guidelines that could establish a scrapie-free status for a country. Unfortunately, the global picture remains incomplete because in many countries confusion still remains regarding the clinical picture of scrapie and information is not available owing to the absence of adequate epidemiosurveillance networks. Currently, the predominant theory is that PrPSc is the infectious agent where host genetic factors play a central role. The precise transmission routes of scrapie and their relative contributions to the overall transmission intensity remain poorly documented and the physiopathology is not fully understood. However, it is evident that the purchase of female sheep from scrapie flocks, sharing pastures with scrapie flocks, sharing breeding rams and genetic host susceptibility are the main risk factors for the spread of the disease. A better understanding of the epidemiology of scrapie would greatly aid the development and evaluation of control and eradication strategies that were mainly based on selective depopulation of infected animals and genetically susceptible and/or related animals and also on the biosecurity and the use of selective genetic breeding programmes in healthy flocks. Some numbers of a new transmissible spongiform encephalopathy (TSE) form in small ruminants (atypical scrapie) have meanwhile been identified by TSE rapid testing using an assay, which also recognizes comparatively less proteinase K-resistant PrPSc. Uncertainties remain regarding the pathogenesis of this new TSE form, as well as regarding its potential transmissibility within the affected species and to other species. Thus far, no bovine spongiform encephalopathy (BSE) cases have been confirmed in sheep under natural conditions (a report of vertical transmission after experimental infection merits attention), but two historical cases of BSE in goats born in the 1990s have been identified. Currently BSE must also be considered in the differential diagnosis of scrapie. The development of prevention and control programmes should be assisted by new scientific findings

Detection and genotyping of bovine diarrhea virus by reverse transcription-polymerase chain amplification of the 5&#039; untranslated region.

&lt;p&gt;A reverse-transcription polymerase chain reaction (RT-PCR) was developed to differentiate the bovine diarrhea virus (BVDV) from other pestiviruses, and to determine the genotype of the BVDV isolates. For this purpose, primer pairs were selected in the 5&#039; untranslated region (5&#039;UTR). The primers BE and B2 were located in highly conserved regions and were pestivirus-specific. Two primer pairs named B3B4 and B5B6 were specific of BVDV genotypes I and II, respectively. With this technique, an amplification product of the expected size was obtained with either the B3B4 or the B5B6 primer pairs for the 107 BVDV isolates tested but not for BDV or CSFV. For some isolates that were grouped in the genotype II, sequence analysis of the PCR fragments confirmed their classification into this genotype.&lt;/p&gt;</p

Specific serum and local antibody responses against Cryptosporidium parvum during medication of calves with halofuginone lactate.

Fecal and serum anti-Cryptosporidium parvum immunoglobulin A (IgA), IgM, and IgG were monitored by an enzyme immunoassay in C. parvum-infected calves after medication with halofuginone lactate. In a first experiment, four groups of five 1-day-old colostrum-fed calves were inoculated with 10(6) oocysts of C. parvum. They were medicated with 0, 30, 60, or 120 micrograms of halofuginone lactate per kg from days 2 to 8 postinfection (p.i.). Unmedicated calves passed large numbers of oocysts between 3 and 14 days p.i. Treatment with 30 micrograms/kg did not completely inhibit oocyst output during medication, whereas 60 and 120 micrograms/kg did. The latter groups passed only a reduced number of oocysts when the drug was withdrawn. In a second experiment, 3- to 6-day-old colostrum-fed calves were divided into three groups of 16 or 17 animals each. All animals had acquired C. parvum infection before arrival at the fattening unit. They were medicated with 0, 60, or 120 micrograms/kg for 7 days beginning on the day of arrival. Unmedicated calves passed large numbers of oocysts from 0 to 21 days. Medication stopped oocyst output at day 7, but some of the calves again passed low numbers of oocysts 7 days after withdrawal of the drug. Experimental infection of unmedicated calves was followed by a rise in local anti-C. parvum IgA and IgM titers. Rising coproantibody levels coincided with falling oocyst output. In halofuginone-medicated and experimentally infected calves, only specific anti-C. parvum IgM levels rose during the first 5 days p.i. Specific IgA levels increased in association with oocyst output after withdrawal of the drug in the 60- and 120-micrograms/kg groups. In naturally infected calves, on the other hand, both specific IgA and IgM levels rose further during medication. Although titers were lower than in unmedicated controls, no significant differences were observed. Both medicated and unmedicated calves were equally protected from a challenge with 10(7) oocysts 16 weeks after the first contact with the parasite