Background
A positive MRZ reaction, as defined by intrathecal IgG production against at least two of its constituents, measles virus (M), rubella virus (R) and varicella zoster virus (Z), is detectable in ~ 63% of patients with multiple sclerosis (MS) and is currently considered the laboratory marker with the highest specificity and positive likelihood ratio for MS. However, M, R and Z are only the most well-established constituents of a broader intrathecal humoral immune response in MS.
Objective
To identify additional anti-microbial antibodies inclusion of which in the classical MRZ panel may result in increased sensitivity without compromising the marker’s high specificity for MS.
Methods
We determined the antibody indices (AIs) for 11 viral and bacterial agents (M, R, Z, herpes simplex virus, Epstein–Barr virus, mumps virus, cytomegalovirus, parvovirus B19, Bordetella pertussis, Corynebacterium diphtheriae, and Clostridium tetani) in paired cerebrospinal fluid and serum samples from patients with MS and disease controls.
Results
A positive ‘classical’ MRZ reaction was found in 17/26 (65.4%) MS patients. The five most frequently positive AIs among patients with MS were M (76.9%), Z (61.5%), R (57.7%), parvovirus B19 (42.3%), and mumps (28%). Addition of parvovirus B19 and mumps virus to the MRZ panel resulted in an increase in sensitivity in the MS group from 65.4% to 73.1%, with 22% of the initially MRZ-negative patients exhibiting a de novo-positive response. The extended MRZ panel (‘MRZplus’) distinguished sharply between MS (≥ 3 AIs in 90% of all positives) and controls (varying diagnoses, from migraine to vasculitis; 0-1 AIs; p < 0.000001). The highest median AI in the MS group was found for parvovirus B19 (3.97), followed by measles virus (2.79).
Conclusion
Inclusion of parvovirus B19 and mumps virus in the test panel resulted in an increase in the sensitivity and discriminatory power of MRZ. Our results provide a strong rational for prospective studies investigating the role of extended MRZ panels in the differential diagnosis of MS.
Experiments on aerobic glycolytic metabolism in tissue cultures during the multiplication of poliomyelitis virus led to varying results. Some authors found the rate unaltered, others observed a transitory, but considerable increase.In this series of experiments aerobic glycolysis was measured after infection of monkey kidney and HeLa cell cultures with all three serotypes of poliomyelitis virus and with ECHO-Virus type 9. Virus multiplication was measured and the cytopathogenic effect observed in the same cultures.At the time of inoculation the cell cultures had varying rates of glycolysis, some none at all. In none of the experiments was virus multiplication associated with a change in glycolytic rate. In some cases a transitory rate increase could be observed after the completion of virus liberation. This phenomenon is not a result of virus multiplication but probably of cytolysis. The capability of glycolytic rate increase in the cell-cultures used was proved with 2.4-dinitrophenol.After the end of the virus multiplication cycle the rate of aerobic glycolysis does not drop suddenly, as does that of respiration and anaerobic glycolysis. This finding is considered to show that respiration and anaerobic glycolysis play the essential part in the energy-donating metabolism of cell-cultures.The increase of the glycolytic rate during enterovirus infection described in the literature is nonspecific with respect to virus multiplication.
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