Increased IGM and IGG anti-NEU5GC antibodies in infectious mononucleosis (IMN): link with multiple sclerosis (MS)?
Abstract
Introduction: Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease which displays an autoimmune component at its overt clinical stage. Among etiological hypotheses, the potential initiating role of EBV in the disease has been raised following works linking EBNA levels and the risk of MS occurrence [1] showing a linkage between the occurrence of IMN and MS. Our hypothesis is that a vigorous production of anti-Neu5Gc in IMN (as indirectly measured by Paul-Bunnell Davidson reaction) may induce brain blood barrier alterations when the EBV primo-infection is contemporary of an extraordinary high frequency of EBV committed T cells and of circulating EBV+ memory B cells[2]. Our aim was to measure anti-Neu5Gc IgG and IgM levels during the IMN and to investigate whether levels of anti-NeuGc could be also increased in MS. Material and Methods: Sera from 49 patients with overt IMN were collected from the University Hospital of Grenoble and Nantes. The gender ratio was 22F/ 27M. The age average was 24 years (range: 7- 65). Two cohorts of EBV negative individuals (n= 45) and healthy individuals (n= 120) were used as controls. A second cohort of 46 patients with proven MS was collected from the University Hospital of Nantes. The gender ratio was 30F/ 16M. The age average was 48 years (range: 22-73). This cohort contained 30 patients presenting a Remitting Relapsing (RR) form (65.2%) and 16 with a Secondary or Primary Progressive (SP-PP) one (34.7%). A cohort of healthy individuals (n= 37) matched for gender and age was used as controls. On these samples, we performed two Elisa [3][4] to quantify anti-Neu5Gc IgG and IgM antibodies. Results: We showed a highly significant increase in anti-Neu5Gc IgM in IMN patients in comparison to EBV negative controls (0.82±0.16 vs. 0.15±0.05 ng/ul; p<0.0001). Anti-Neu5Gc IgG were also, though less dramatically, increased (3.64±0.6 vs. 2.78±0.57ng/ul; p=0.04). The values obtained in IMN differed significantly to healthy individuals (0.82±0.16 vs. 0.2±0.03 ng/ul;p<0.0001 for IgM and 3.63±0.6 vs. 2.74±0.3 ng/ul; p= 0.01 for IgG). The levels of anti-α1-3Gal epitopes, an other type of «xeno» antibody against a sugar not synthesized by normal individuals were also increased during IMN (12.4±1.1 vs. 9.67±1.46 ng/ul for EBV negative controls and vs. 11.7±3.4 ng/ul for healthy individuals; p<0.0001 for both). We found neither increase in anti-Neu5gc antibodies in this small MS patient cohort (p=0.8 for IgM and p=0.84 for IgG), nor in RR or SP-PP subgroups. We found no correlation between the anti-Neu5Gc titers and age or gender of IMN or MS patients, or of healthy individuals. Conclusion: Despite the fact that EVB does not express Neu5Gc, anti-Neu5Gc antibodies are strongly increased in IMN patients, suggesting that uptake of Neu5Gc from dietary sources by EBV infected cells induces them to become more immunogenic during the acute disease. However our data did not evidence higher anti-Neu5Gc antibodies in established MS.