Non invasive surveillance of JCV reactivation in blood and urine from natalizumab treated MS patients, blood donors and immunocompromised patients identifies two PML cases in HIV and congenital immunodeficiency patients

A longitudinal screening for JC polyomavirus (JCV) was performed in natalizumab-treated multiple sclerosis (MS) patients, immunocompromised patients and immunecompetent subjects to identify the incidence of JCV reactivation in these different groups. Thirty-eight MS patients were selected for natalizumab-treatment: 23 patients were treated for 12 months, 9 for 24 months and 4 for up to 28 months. Samples were collected from 51 untreated MS patients, 105 patients with other neurological diseases (OND), 186 kidney transplant recipients, 67 haemopoietic stem cell transplant (HSCT) patients, 71 outpatients and 63 blood donors. JCV DNA was detected by Real Time PCR. Cell mediated immunity by ImmuKnow was determined in 70 samples from 36 subjects by measuring the ATP levels in PHA-activated CD4 T-lymphocytes. All 115 sequential blood samples from the 38 natalizumab-treated MS patients resulted JCV negative. Instead, JCV DNA was quantified in 20 blood samples from 3 patients with haemorrhagic cystitis caused by BKV reactivation, 1 patient with a JCV associated nephropathy, 1 AIDS patient and a patient with congenital immunodeficiency. Two blood samples, with 3x10^5 and 2.5x10^3 JCV DNA copies/ml, provided the etiologic diagnosis of PML in the AIDS patient and the patient affected with congenital immunodeficiency. The ATP concentration in this patient's CD4+ cells was repeatedly barely detectable indicating severe depression of cell mediated immunity. PCR detection of JCV DNA in a cerebral spinal fluid sample (AIDS patient) and a brain biopsy (congenital immunodeficient patient) and magnetic resonance imaging completed the PML diagnosis. JCV viruria was prevalent in all groups with 27% in blood donors, 18% in kidney transplant recipients, 30% in HSCT patients and similar values in OND and natalizumab-treated MS patients, 40% and 37%, respectively. JCV DNA was detected in urine in 11 of the 38 natalizumab-treated MS patients at baseline, 8/23 patients treated for 12 months, 4/9 patients treated for 24 months. Of the 4 MS patients natalizumab-treated for 28 months, 2 were constantly JCV negative and 2 were intermittently JCV positive. This preliminary report shows that there is no evidence that JCV increases in natalizumab treated MS patients and that the incidence of JCV reactivation in blood and urine in MS patients natalizumab treated up to 28 months is comparable with the incidences in OND patients.