Sunday, December 05, 2010

H1N1 & The Non-Protective Antibody Response

 

 

 

# 5117

 

 

Normally, with seasonal influenza, it is the elderly and frail that make up 90% of the hospitalizations and deaths each year. The average age of death from seasonal flu in the US has been estimated to be about 76.

 

The mean age of death from the 2009 H1N1 virus,  has been calculated to be half that, or 37.4 years (see Study: Years Of Life Lost Due To 2009 Pandemic).

 

Although the 2009 pandemic was `mild’ in terms of the total number of people killed, it was anything but mild in the way it attacked a small percentage of – mostly young adult – patients.

 

A few blogs from the past year on how novel H1N1 presented differently than seasonal flu:

 

Canada: H1N1 Sent More To ICU Than Seasonal Flu
NIH: Post Mortem Studies Of H1N1
Pathology Of Fatal H1N1 Lung Infections

 

While the reasons why were not clear, it was apparent that in a small subset of patients, H1N1 produced severe – sometimes fatal – lung damage.

 

We’ve an intriguing study published today in the journal Nature Medicine that theorizes why those between the ages of 20 and 50 saw more severe illness from the pandemic than those who were either younger or older.

 

The culprit, researchers suggest, was a non-protective antibody response, that they believe attacked the patient instead of the virus.

 

First a link to the study (which is behind a pay wall) & abstract, followed by a few short excerpts from a press release describing some of the findings.  After that, a link to a sciencemag.org story on the study, and lastly, a link to a Nature News feature story about this study.

 

 

Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

Ana Clara Monsalvo,Juan P Batalle,M Florencia Lopez,Jens C Krause,Jennifer Klemenc,Johanna Zea Hernandez,Bernardo Maskin,Jimena Bugna,Carlos Rubinstein,Leandro Aguilar,Liliana Dalurzo, Romina Libster, Vilma Savy,Elsa Baumeister,Liliana Aguilar, Graciela Cabral,Julia Font,Liliana Solari,Kevin P Weller,Joyce Johnson,Marcela Echavarria,Kathryn M Edwards,James D Chappell,James E Crowe Jr,John V Williams,Guillermina A Melendi& Fernando P Polack et al.

 

The press release (which I’ve only excerpted), comes from Vanderbilt University Medical Center.

 

Over-reactive immune system kills young adults during pandemic flu

(Excerpts)

In a paper published Dec. 5 in Nature Medicine, Fernando Polack, M.D., the Cesar Milstein Associate Professor of Pediatrics at Vanderbilt, and colleagues in Argentina and Nashville provide a possible explanation for this alarming phenomenon of pandemic flu. The study's findings suggest people are made critically ill, or even killed, by their own immune response.

 

"Every time there is an influenza pandemic there is a large proportion of younger, or middle-aged adults who die. We have always explained these deaths, based on presumed virulence of virus, or getting bacterial infection at the same time. We now have vaccines and antibiotics, but still we see middle-aged individuals who die," Polack said.

 

<SNIP>

 

"We have seen this before. Where non-protective antibody responses are associated with an immune-based disease in the lung," Polack said.

 

Polack has previously published evidence that a first-line immune response, primed by an imperfect antibody, can overreact in a violent and uncontrolled fashion. Patients die from lung damage inflicted by their own immune system. A molecule called C4d, a product of this biochemical cascade (the complement system), is a marker for the strength of the response.

 

In adults who died during the 2009 H1N1 pandemic, high levels of C4d in lung tissues suggest a massive, potentially fatal activation of the complement system.

(Continue . . . )

 

 

You can find a pretty good overview of this study in an article that appears today in Science Magazine.

 

How Swine Flu Killed the Healthy

by Kristen Minogue on 5 December 2010, 1:00 PM

But perhaps the most complete summary can be found in this Nature News story, which also contains an interesting caveat about what all of this could mean for the development of `universal’ flu vaccines. 

Exposure to seasonal flu weakened armour against H1N1

Faulty antibodies from previous infections boosted severity of swine flu in the middle-aged.