Background: Oligoclonal bands (OCB) are detected in the cerebrospinal fluid (CSF) in more than 95% of patients with multiple sclerosis (MS) in the Western hemisphere. Here we evaluated the intrathecal, polyspecific antiviral immune response as a potential diagnostic CSF marker for OCB-negative MS patients.
Methodology/principal Findings: We tested 46 OCB-negative German patients with paraclinically well defined, definite MS. Sixteen OCB-negative patients with a clear diagnosis of other autoimmune CNS disorders and 37 neurological patients without evidence for autoimmune CNS inflammation served as control groups. Antibodies against measles, rubella, varicella zoster and herpes simplex virus in paired serum and CSF samples were determined by ELISA, and virus-specific immunoglobulin G antibody indices were calculated. An intrathecal antibody synthesis against at least one neurotropic virus was detected in 8 of 26 (31%) patients with relapsing-remitting MS, 8 of 12 (67%) with secondary progressive MS and 5 of 8 (63%) with primary progressive MS, in 3 of 16 (19%) CNS autoimmune and 3 of 37 (8%) non-autoimmune control patients. Antibody synthesis against two or more viruses was found in 11 of 46 (24%) MS patients but in neither of the two control groups. On average, MS patients with a positive antiviral immune response were older and had a longer disease duration than those without.
Conclusion: Determination of the intrathecal, polyspecific antiviral immune response may allow to establish a CSF-supported diagnosis of MS in OCB-negative patients when two or more of the four virus antibody indices are elevated.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392215 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040431 | PLOS |
Zhongguo Dang Dai Er Ke Za Zhi
January 2025
Department of Neonatology, Children's Hospital of Chongqing Medical University/National Clinical Research Center for Child Health and Disorders/Ministry of Education Key Laboratory of Child Development and Disorders/Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Chongqing 400014, China.
Neonates are susceptible to respiratory viral infections, with outbreaks reported in areas with a high population of neonates, such as postpartum care centers and neonatal wards. While specific antiviral drugs are currently available for influenza, symptomatic supportive treatment remains the primary approach for respiratory syncytial virus (RSV), making prevention particularly important. The article closely follows the "Expert recommendations for the prevention of common respiratory viral infections in neonates" and provides an in-depth interpretation of recent breakthroughs in RSV prevention.
View Article and Find Full Text PDFIntroduction: 58 million people worldwide are chronically infected with hepatitis C virus (HCV) and are at risk of developing cirrhosis and hepatocellular carcinoma (HCC). Direct-acting antivirals are highly effective; however, they are burdened by high costs and the unchanged risk of HCC and reinfection, making prophylactic countermeasures an urgent medical need. HCV high genetic diversity is one of the main obstacles to vaccine development.
View Article and Find Full Text PDFBMC Infect Dis
January 2025
Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China.
Objective: Long-term management of people living with HIV (PLWHs) often relies on CD4 T cell counts for assessing immune recovery, yet a single metric offers limited information. This study aimed to explore the association between the CD4/CD8 ratio and T lymphocyte activities in PLWHs.
Methods: 125 PLWHs and 31 HIV-uninfected controls (UCs) were enrolled and categorized into four groups based on their CD4/CD8 ratios: extremely low ratio (ELR) group: 0.
Nat Commun
January 2025
Department of Biochemistry and Structural Biology, UT Health San Antonio, San Antonio, TX, USA.
SAMHD1 is a dNTPase that impedes replication of HIV-1 in myeloid cells and resting T lymphocytes. Here we elucidate the substrate activation mechanism of SAMHD1, which involves dNTP binding at allosteric sites and transient tetramerization. Our findings reveal that tetramerization alone is insufficient to promote dNTP hydrolysis; instead, the activation mechanism requires an inactive tetrameric intermediate with partially occupied allosteric sites.
View Article and Find Full Text PDFNat Commun
January 2025
Université Paris Cité, Institut Cochin, CNRS, INSERM, Paris, France.
Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but the effect of IFN-α on the antigen repertoire of HLA Class I (HLA-I) in pancreatic β-cells is unknown. Here we characterize the HLA-I antigen presentation in resting and IFN-α-exposed β-cells and find that IFN-α increases HLA-I expression and expands peptide repertoire to those derived from alternative mRNA splicing, protein cis-splicing and post-translational modifications. While the resting β-cell immunopeptidome is dominated by HLA-A-restricted peptides, IFN-α largely favors HLA-B and only marginally upregulates HLA-A, translating into increased HLA-B-restricted peptide presentation and activation of HLA-B-restricted CD8 T cells.
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