Brief Communications in 2009

A serious complication of blood transfusions is transfusion-related acute lung injury, which can be caused by antibodies in the donor blood that recognize and activate host neutrophils. Andreas Greinacher and his colleagues now determine the molecular identity of the antigen recognized by one of these antibodies, termed human neutrophil alloantigen-3a, as a variant of the choline transporter-like protein-2. This finding opens the door to systematic screening of blood donors and recipients.

Giovanni Monteleone and his colleagues show that the T cell-derived cytokine interleukin-21 is a new potential therapeutic target for psoriasis. Interleukin-21 seems to act directly on keratinocytes, stimulating them to proliferate and causing epidermal hyperplasia.

There are three established HIV-1 lineages, M, N and O, which arose after cross-species transmission of simian immunodeficiency virus circulating in chimpanzees. An unusual variant of HIV-1 has now been identified that seems to be the prototype of a new lineage derived from gorillas.

The phase 2b trial of Merck's recombinant adenovirus type 5–based HIV-1 vaccine was halted as the vaccine seemed to have increased HIV-1 acquisition in vaccine recipients who had preexisting immunity to the adenovirus vector. One theory to explain these results is that the preexisting antibody response to the vector may have been a surrogate for increased vector-specific CD4⁺ T cells, which would have been amplified after vaccination and may have served as increased target cells during subsequent HIV-1 exposure. Daniel Barouch and his colleagues and Michael Betts and his colleagues now challenge this view.

The phase 2b trial of Merck's recombinant adenovirus type 5-based HIV-1 vaccine was halted as the vaccine seemed to have increased HIV-1 acquisition in vaccine recipients who had preexisting immunity to the adenovirus vector. One theory to explain these results is that the preexisting antibody response to the vector may have been a surrogate for increased vector-specific CD4⁺ T cells, which would have been amplified after vaccination and may have served as increased target cells during subsequent HIV-1 exposure. Daniel Barouch and his colleagues and Michael Betts and his colleagues now challenge this view.

Immunosuppressive regimens used to prevent rejection of transplanted organs are associated with many adverse side effects. Weaver et al. report that by combining the use of a CD2-targeting reagent (alefacept) with a co-stimulation blockade–based protocol, they can prolong survival of kidney allografts in macaques while avoiding the use of standard immunosuppressive agents.

It has been a long-held belief that the hormone ghrelin is activated when an animal is hungry, inducing the brain to increase food intake. Now, Matthias Tschöp and his colleagues show in vivo that it is not the deficiency of calories per se that activates ghrelin, but rather the presence of energy-rich medium-chain dietary fats.

Neutrophils release neutrophil extracellular traps (NETs), chromatin fibers that can ensnare bacteria. In small-vessel vasculitis (SVV), a chronic inflammatory condition linked to antineutrophil autoantibodies, these NETs express SVV-associated autoantigens, accumulate in inflamed kidneys and promote the autoimmune response against neutrophils in people with SVV.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome that is often difficult to treat. Hiroshi Watanabe and coworkers now show that flecainide, an approved drug known to inhibit sodium channels, is able to target the underlying cause of CPVT by inhibiting calcium release through the ryanodine receptor. Flecainide prevented arrhythmia in a mouse model of CPVT and was also effective when tested in two individuals with CPVT.

The neurotoxic Aβ peptide is produced after traumatic brain injury. Mark P. Burns and his colleagues show that inhibiting the enzymes involved in Aβ production can block the neuron death and neurological dysfunction that occurs after traumatic brain injury.

Studies of hepatitis C virus replication in cell culture have suggested that certain microRNAs are required for efficient virus replication and that they may be involved in the antiviral effect of interferon. A study in humans infected with the virus provides a new perspective.