Den tvivlsomme vaccine - BCG-vaccinen og den globale tuberkulose-epidemi, 1948-65

I årene efter anden verdenskrig truede tuberkulose med at antage epidemiske proportioner, ikke mindst i Afrika, Asien og Latinamerika. I den situation valgte WHO – ansporet af et skandinavisk vaccinationsinitiativ – at anbefale den kontroversielle BCG-vaccine. Ført i 1959 foretog WHO en systematisk undersøgelse af de tilgængelige og modstridende oplysninger om vaccinens effektivitet. I undersøgelsen nedprioriterede WHO imidlertid oplysninger, der stillede spørgsmål ved vaccinens værdi i bekæmpelsen af tuberkulose og fortsatte ufortrødent med at anbefale vaccinen. Artiklen illustrerer, hvordan fornemmelsen af at stå over for en epidemi tvang WHO til at handle på utilstrækkeligt grundlag, men også medicinsk stædighed og institutionel inerti

Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-α and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis

B cells are involved in driving relapsing-remitting multiple sclerosis (RRMS), as demonstrated by the positive effect of therapeutic B-cell depletion. Aside from producing antibodies, B cells are efficient antigen-presenting and cytokine-secreting cells. Diverse polyclonal stimuli have been used to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide. The proportions of B cells producing TNF-α or IL-6 after stimulation with MBP were higher in RRMS patients than in healthy donors, indicating a pro-inflammatory profile for self-reactive patient B cells. In contrast, polyclonal stimulation with PMA + ionomycin and MBP revealed no difference in cytokine profile between B cells from RRMS patients and healthy donors. Expanded disability status scale (EDSS) as well as multiple sclerosis severity score (MSSS) correlated with reduced ability of B cells to produce IL-10 after stimulation with MBP, indicative of diminished B-cell immune regulatory function in patients with the most severe disease. Moreover, EDSS correlated positively with the frequencies of TNF-α, IL-6 and IL-10 producing B cells after polyclonal stimulation. Patient-derived, IL-10-producing B cells presented MBP85-99 poorly, as did IL-6-producing B cells, particulary in the healthy donor group. B cells from MS patients thus present antigen to T cells in a pro-inflammatory context. These findings contribute to understanding the therapeutic effects of B-cell depletion in human autoimmune diseases, including MS

BEYOND THE HIGH MODERNIST MOMENT – AN INTERVIEW WITH JAMES C. SCOTT

Interview with James C. Scott on 'Seeing like a State

MODERNITETSFORESTILLINGER OG MODERNISERINGSBESTRÆBELSER I GLOBALT PERSPEKTIV

Indledning til temp nr. 12 - temanumme