HHV‐6 A‐ or B‐specific P41 antigens do not reveal virus variant‐specific IgG or IgM responses in human serum

Abstract

The etiology of multiple sclerosis (MS) remains unknown, but there are indications of a role of human herpesvirus 6 (HHV-6), especially variant A, in the pathogenesis. Higher serum antibody reactivity against an HHV-6 early protein, p41, has been found in MS cases than in controls. The antigen, however, was purified from infected cells with a monoclonal antibody also reactive with a protein (p38) likely to be of cellular origin. To avoid serological crossreactivity with the cellular protein, recombinant p41 proteins from HHV-6A strain GS and HHV-6B strain Z29 were expressed as glutathione-S-transferase fusion proteins (p41-GST), and used as antigens in an enzyme-linked immunosorbent assay (ELISA). p41 variant specific monoclonal antibodies reacted strongly with the respective recombinant proteins. Serum IgM and IgG reactivities with the recombinant p41 antigens were analysed in patients with manifest MS, patients with optic neuritis, patients with other neurological diseases, and in one group of healthy controls. All sera were HHV-6 IgG seropositive by immunofluorescence. The serum IgM or IgG reactivities against the recombinant p41 antigens did not differ significantly between the groups, and the reactivities against the variant A and B antigens were identical. In many samples, the reactivity was very low. The results indicate that p41 is not an optimal target for HHV-6 serology studies, and that the data obtained with the p41 antigen prepared from infected cells (possibly including also p38) should be interpreted with caution.

Recombinant VP6-based enzyme-linked immunosorbent assay for detection of immunoglobulin G antibodies to Eyach virus (genus Coltivirus)

“…In addition, the testing with anti-GST antibodies has ruled out the presence of any contaminating GST following cleavage of the GST moiety prior to coating. Accordingly, there is no need to run a control GST ELISA (Brénière et al, 2002;Xu et al, 2002).…”

Human Herpesvirus 6 Infection as a Trigger of Multiple Sclerosis

“…14, 15,17,28 Four studies were classified as A quality but did not reach statistical significance. 13,16,18,19 Of those 4 studies, 2 considered mean antibody titers rather than an arbitrary positive titer. 18,19 Four studies were classified as intermediate quality (B), and none of them showed a statistically significant difference between MS patients and controls.…”

“…13,16,18,19 Of those 4 studies, 2 considered mean antibody titers rather than an arbitrary positive titer. 18,19 Four studies were classified as intermediate quality (B), and none of them showed a statistically significant difference between MS patients and controls. 20,[24][25][26] One of those studies considered mean antibody titers, 20 and another reported only that the IgG titers of MS patients were higher than those of controls without providing absolute values.…”

“…Two studies were classified as A quality and reached statistical significance when correlating IgM anti-HHV-6 antibodies with MS. 16,28 Three more studies were classified as A quality but did not reach statistical significance when comparing MS patients and controls. 13,19,20 Of these 3 studies, 2 reported mean antibody titers. 19,20 Two studies were classified as B quality.…”

“…13,19,20 Of these 3 studies, 2 reported mean antibody titers. 19,20 Two studies were classified as B quality. 24,25 Ongradi et al 24 reached statistical significance and reported only "high" and "low" antibody titers in MS patients and controls without providing actual values, whereas Ablashi et al 25 did not find significant differences in titers.…”