In summary, we were able to demonstrate unique reactivity to SPEB in human sera and kidney biopsies of APSGN suggesting a significant role of this toxin in the pathogenesis of acute post-streptococcal glomerulonephritis.
SummaryExamination of the extracellular products of nephritis(+) and nephritis(-) group A streptococci revealed the presence of a 46-kD protein secreted by nephritogenic strains that binds to human plasmin. Immunological data revealed that this protein, called nephritis plasmin binding protein (NPBP), is not related to group A streptokinase nor to a recently described streptococcal dehydrogenase protein. The binding of human plasmin to this protein can be blocked by e-amino caproic acid, indicating the importance of lysine groups in the binding process. Mutanolysin extracts of cell walls from these nephritogenic strains probed with anti-NPBP antibody were negative for cell wall-bound NPBP. Serological data with acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever sera indicated that the protein reacts preferentially with APSGN sera. Amino acid sequence analysis and immunological reactivity suggest NPBP is the streptococcal pyrogenic exotoxin B precursor, also previously described as zymogen (streptococcal proteinase precursor). The secretion of both group A streptokinase and a secreted plasmin binding protein in the same nephritogenic strain raises an intriguing hypothesis of the mechanism of action of this protein in APSGN.
Given the clinical and pathological nature of Multiple Sclerosis (MS), a viral infection has long been hypothesized as part of the etiology. In this study we investigated the possibility that the human herpesvirus-6 (HHV-6) is present in a dormant or active phase in the tissue of MS patients, specifically oligodendrocytes. Using PCR assays of MS and non-MS brain sections with primers prepared against the HHV-6 structural protein 101, the results demonstrated that 36% of MS brains were positive for the virus, while 13.5% of non-MS brains were positive. Antibody to the HHV-6 structural protein was also used in immunohistochemical experiments in brain tissue. 47% (7/15) of MS brains were positive for HHV-6, whereas 0/16 controls were positive. In addition, MS patients demonstrated high immune reactivity to this virus, even when compared to auto-immune diseases, which might cause polyclonal activation. Sera obtained from MS and control patients revealed that the IgM response to the HHV-6 virus was significantly elevated in 80% patients compared to 16% non-MS controls, P<.001. The above experiments strongly suggest that a significant number of MS brain samples contain HHV-6 antigens and genomic fragments in a dormant or active phase compared to control specimens and that MS patients mount a brisk, early IgM response.
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