Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings.

BACKGROUND: Two human herpesviruses, human herpesvirus 6 (HHV-6), and Epstein-Barr virus (EBV), have been repeatedly linked to multiple sclerosis (MS). OBJECTIVE: The aim of this study was to investigate HHV-6 and EBV reactive oligoclonal bands (OCBs), and viral DNA in the intrathecal compartment in MS. METHODS: The reactivity of OCBs in cerebrospinal fluid (CSF) for EBV and HHV-6 antigens and stability of virus reactive OCBs over time were studied in a well-characterized MS patient cohort. Associations between virus reactive OCBs and viral DNA in CSF (and any clinical and/or radiological findings) were investigated. RESULTS: Of patients with MS, 38% had OCBs reactive to either one of the viruses studied, compared to none in the patients with other inflammatory neurological diseases (p=0.005). The banding pattern of virus reactive OCBs remained the same over time. Furthermore, MS patients with viral DNA in CSF had more contrast enhancing lesions (CELs). CONCLUSION: The stable presence of herpesvirus reactive OCBs in CSF further strengthens the association of MS with these viruses. The finding that herpesviruses might be linked to the appearance of active lesions warrants investigation of new therapeutic strategies to treat these viruses in MS.

HHV-6 infection in multiple sclerosis. A clinical and laboratory analysis.

BACKGROUND AND PURPOSE: To elucidate the role of human herpesvirus-6 (HHV-6) in the development of multiple sclerosis (MS). PATIENTS AND METHODS: Nine patients with MS and with acute or chronic HHV-6 infection were evaluated. RESULTS: Intrathecal antibody production to HHV-6 and oligoclonal IgG bands in the cerebrospinal fluid (CSF) was observed in two patients with a clinically definite MS and chronic HHV-6 infection (based on the presence of HHV-6 specific antibodies in the CSF). A temporal association between the symptoms of clinically possible MS and acute primary HHV-6A infection (based on avidity of HHV-6 specific antibodies) was observed in two patients. CONCLUSIONS: Human herpesvirus-6 infection may be an associated agent in some MS cases. Viral studies are needed to identify a possible viral etiology and give specific therapy.

Early thrombin generation and impaired fibrinolysis after SCT associate with acute GVHD.

The evolution of coagulation and fibrinolysis has not been thoroughly evaluated in allogeneic SCT. In this pilot study, we characterized the adaptive mechanisms of coagulation and fibrinolysis during allogeneic SCT and 3-month follow-up and studied possible associations with outcome, including acute GVHD. Thirty patients underwent SCT for a haematological malignancy after myeloablative conditioning. Nineteen patients received the transplant from an HLA-identical sibling and 11 from an unrelated donor. GVHD prophylaxis consisted of CYA and MTX, with methylprednisolone in sibling transplants. Serial coagulation and fibrinolytic activity markers were assessed, including prothrombin fragments 1+2 (F1+2), thrombin time, D-dimer, tissue-type plasminogen-activator (tPA) and plasminogen-activator inhibitor (PAI-1). Early during conditioning therapy, F1+2 and D-dimer increased threefold indicating thrombin generation and fibrin turnover. TPA activity peaked before engraftment, concurring with diminished PAI-1. At 10 days after transplantation shortened thrombin time (<15 s), F1+2 exceeding 0.7 nmol/L and PAI-1 3.0 IU/mL were associated with the development of GVHD. In conclusion, early maladaptation, that is, upregulated thrombin generation and inhibition of fibrinolysis, occurred in one-third of the SCT patients associating with the development of GVHD, a finding suggesting an interplay between coagulation and immunology during SCT.

Confirmed primary HHV-6 infection in children with suspected encephalitis.

HHV-6 infection has been associated with neurological symptoms in children. Two variants of human herpes virus 6, HHV-6A and HHV-6B, have been identified. Their role in neurological infections is poorly understood. We studied 53 children with suspected encephalitis for HHV-6A (strain GS) and HHV-6B (strain Z29) antibodies using an indirect immunofluorescence test. Primary infection was separated from past infection by an IgG-avidity test. The identified primary infections were studied for HHV-6 specific DNA by PCR. Forty-one children of 53 had IgG antibodies to HHV-6. Six children had low avidity of HHV-6 IgG antibodies indicating acute primary infection; four to type A, one to B, and one to both types. By serology, HHV-6 viral etiology was suggested in 6/53 (11.3%) of cases. One of the six patients with primary infection had HHV-6 DNA in serum and two in CSF. The children with primary HHV-6 infection were significantly younger than the whole series, 2.3 years vs. 6.4 years. We conclude that primary HHV-6 infection appears to be an important associated or causative agent in neurological infections of young children, and it can be confirmed from a single serum specimen using the IgG-avidity test.

Evidence for human herpesvirus 6 variant A antibodies in multiple sclerosis: diagnostic and therapeutic implications.

Human herpesvirus 6 (HHV-6) has been linked to the pathogenesis of multiple sclerosis (MS). HHV-6 antibodies in serum and cerebrospinal fluid (CSF) of 27 patients with clinically definite MS (CDMS) were compared with age- and sex-matched controls, including various other neurological diseases and symptoms (OND). In addition, we studied a series of 19 patients with clinically or laboratory supported possible MS (CPMS). Seroprevalence to HHV-6A was 100% in patients with MS, both in CDMS and CPMS, compared to 69.2% in patients with OND (P = .001 and .007). The mean immunoglobulin G (IgG) titers were significantly higher in patients with CDMS and CPMS than in controls (P = .005 and .00002). The proportion of acute primary infections without CSF involvement was similar in all groups; however, primary infections with intrathecal HHV-6 antibody production were more frequent in MS. In CSF, HHV-6A-specific antibodies were present in three (11.5%) and four (21.1%) patients with CDMS and CPMS, compared to none with OND (P = .06 and .01, respectively). Serological suggestions to HHV-6A infection occurred more often in both CDMS and CPMS than in OND (14.8% versus 21.1% versus 3.8%). We conclude that a subpopulation of MS patients, and even a greater proportion of possible MS subjects, has serological evidence of HHV-6A infection, which might provide new markers for diagnosis and therapy.