Friday, June 24, 2011

Innate vs Adaptive Immune system

Check out the above website. Especially the nice break down of innate vs adaptive immune system.

Friday, June 17, 2011

FDA approves Belatacept (NULOJIX) for use in kidney transplantation.

It’s been a long time since the FDA approved a new drug for transplantation which makes this news very exciting.  On June 16th Bristol-Myers Squibb announced that the FDA approved the use of NULOJIX (Belatacept) for use in kidney transplantation as an induction and maintenance agent in combination with mycophenolate mofetil and corticosteroids.  The FDA reviewed the Benefit and Benefit EXT trials prior to coming to their conclusion. 
Belatacept is a selective T-cell co-stimulation blocker that is administered IV which offers comparable results to cyclosporine.  Though the acute rejection rate seems to be slightly higher with Belatacept than cyclosporine, trials reveal a higher GFR in the Belatacept arms at 3 years of follow up.  The obvious hope is that the use of Belatacept will avoid calcineurin inhibitor nephrotoxicity in kidney transplant recipients improving long term allograft outcome.  The major concern with Belatacept is an increased risk for PTLD seen in many of the trials.  For this reason it is contraindicated in EBV seronegative patients or patients with unknown EBV serostatus.  To address the concern of PTLD Bristol-Myers Squibb established the ENLiST Registry.  The registries purpose is to determine the incidence of PTLD, CNS PTLD, and PML in US adult EBV seropositive kidney transplant recipients treated with Belatacept.
Belatacept is administered IV over 30 minutes and the recommended dosing is 10 mg/kg on the day of transplantation then on day 5, then at the end of weeks 2, 4, 8, and 12. After week 16 it is recommended that the maintenance dose be 5 mg/kg every 4 weeks.

by Dr. Vinay Nair

Wednesday, June 15, 2011

Human Herpes Virus – 6: An uncommon but potentially treatable infectious agent in transplant recipients

HHV-6 is a DNA virus part of the beta-herpesvirus family and can be divided into HHV-6 A and B.  Primary infection is mild and occurs usually in childhood; therefore the majority of healthy adults have serologic evidence of prior infection.  HHV-6 can re-activate in the immunocompromised transplant recipient leading to asymptomatic viral replication or less commonly active infection.  The highest prevalence by pcr has been shown to occur in bone marrow transplant recipients (28% to 75%) but viral replication has also been shown to occur in liver (28% to 32%) and renal transplant recipients (23% to 36%).  Although asymptomatic viremia is common, clinically active infection carries a high mortality and may be susceptible to specific antiviral treatments.   
How does HHV-6 infection present?
HHV-6 infection commonly presents with high fever often associated with leukopenia, and encephalitis between 2-4 weeks post transplantation.  Other clinical manifestations include pneumonitis, hepatitis, colitis and bone marrow suppression.  Rash typical of a leukocytoclastic vasculitis can also be seen.  Encephalitis may be associated with seizure activity and hyponatremia.  Encephalitis is more commonly seen in BMT patients but has been described in solid organ transplant patients as well.  HHV-6 infections commonly co-exist with other viral infections including CMV. 
HHV-6 reactivation has also been associated with drug induced hypersensitivity syndromes, malignancies, multiple sclerosis, fulminant hepatitis and mycocarditis though causality has not been demonstrated.
What are the associated laboratory and imaging findings?
CBC: Bone marrow suppression, leucopenia, thrombocytopenia
Chemistry: Transaminitis, hyponatremia
CSF:  High lymphocyte cell count with elevated protein.  HHV-6 can be detected in CSF by pcr. 
MRI of brain:  Symmetric non-enhancing white matter lesions.  MRI may be normal in patients infected with HHV-6.
How can you diagnose active infection?
Serologic testing:  Sensitivity varies and most tests cross react with HHV-7.  A fourfold increase in titers or seroconversion is considered diagnostic.
Virus culture from affected tissue or blood can be done but are difficult to perform.
Viral detection:  Virus may be present in PMBC’s of patients with latent infection leading to a “false” positive pcr.   Therefore HHV-6 should be identified in affected tissue or acellular plasma or serum. 
What are the treatment options?
No therapy has been clearly documented to treat HHV-6 although several agents with in-vitro activity have been tried.  Ganciclovir is effective against HHV-6B but may not be active against HHV-6A (minority of infections).  Foscarnet has activity against both A and B however; its use is complicated by nephrotoxicity.  In severe cases both agents can be tried and whenever possible a reduction in immunosuppression should be considered.


Dr. Vinay Nair

Tuesday, June 7, 2011

Sunday, June 5, 2011

BANFF 2011

The agenda for the meeting of Banff in Paris