http://allergycases.org/2005/10/innate-immune-system-short-review.html
Check out the above website. Especially the nice break down of innate vs adaptive immune system.
Friday, June 24, 2011
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.
Read the full press release by BMS: http://www.bms.com/news/press_releases/pages/default.aspx?RSSLink=http://www.businesswire.com/news/bms/20110616006683/en&t=634438496608678094
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.
References:
By
Dr. Vinay Nair
Tuesday, June 7, 2011
Monday, June 6, 2011
Sunday, June 5, 2011
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