During the early days of the AIDS pandemic, there was considerable concern that the virus which causes the disease, HIV, could change from a pathogen that required close physical contact to spread to one that could spread by respiratory droplets like a cold or the flu. Had this occurred, there almost certainly would have been a catastrophic depopulation of large sections of the earth. Although HIV did cause a devastating pandemic, our worst fears for this virus were never realised.
The 2009 pandemic H1N1 virus does spread via respiratory droplets. The percent of people who are infected who die from this virus is not clear. Despite repeated media reports (and one underpowered study) that claim that this virus is no worse than “regular” flu, there is substantial evidence that it has killed many people who would have been considered at low risk of death by influenza.
I previously wrote about an Australian study which suggested that a subset of patients infected with pandemic H1N1 exhibited a form of immune system dysfunction – a deficiency of IgG2. Now, a new study from Italy (hat-tip DryHeat and Pixie) identifies a different immune system dysfunction in some patients who had been infected with pandemic H1N1 – a deficiency of plasmacytoid dendritic cells. In both the Australian and Italian studies, patients with immune deficiency were more likely to suffer severe symptoms. Thus, we now have two independent studies suggesting a correlation between pandemic H1N1 infection, immune deficiency and severe disease.
It is an old saying in science that correlation does not equal causation. Neither the Australian nor the Italian studies were designed to determine whether pandemic H1N1 caused immune deficiency. It is possible that the patients in the studies had a pre-existing immune deficiency which made them more susceptible to adverse outcomes from the pandemic H1N1 virus. However, it is important to point out that no genetic condition has been identified as causative for either of these deficiencies. It is also worth pointing out that there is another virus which causes the same deficiency associated with pandemic H1N1 – HIV.
From Chehimi et al. (2002):
Dendritic cells (DC) have an instrumental role in the activation and function of both innate and adaptive immune responses. In humans, at least two distinct DC subsets have been characterized based on phenotypic markers: the myeloid DC (MDC) and the plasmacytoid DC (PDC). Both subsets are critical producers of cytokines (IL-12 for MDC and type I/II IFNs for PDC) and are functionally different. We show in this study that HIV+ individuals have a significant decrease in the number of the Lin–HLA-DR+CD123+ and BDCA-2+ PDC compared with uninfected donors (p = 0.0001). HIV+ individuals also have a sustained impairment in viral-induced IFN- production (p < 0.0001). The decrease of the PDC subsets did not correlate with CD4 count or viral load and was not reversed in subjects under virally suppressive treatment, suggesting an irreversible change after infection.
Compare these results with those recently reported for pandemic H1N1. From Lichtner et al. (2010):
The aim of our work was to characterize the immunological response in patients affected by H1N1 flu pneumonia. In particular natural immunity was studied and a long follow-up was performed. Plasmocytoid dendritic cells (pDC), which are the main producers of antiviral natural substances such us alpha interferon, were dramatically impaired in the acute phase of the disease in all patients. The most interesting founding was that these cells persisted very low also several months after the recovery of the disease.
The two studies found that the same cell type, plasmacytoid dendritic cells (PDCs), were reduced in patients after infection with either HIV or pandemic H1N1. In the case of HIV, there is little doubt that the virus caused the deficiency. In the case of pandemic H1N1, we don’t know for sure that the virus is causing the deficiency.
One of the insidious features of AIDS is that we did not know how bad it would be until years after HIV had started spreading. This is because the immune deficiency did not kill directly, but rather, killed by leaving people open to opportunistic infections which were the reported causes of death. Serious symptoms are often not observed until years after infection. It is also important to realise that the progression of AIDS from infection to significant disease is extremely variable among different people – from two weeks to more than 20 years.
One study associating pandemic H1N1 with immune deficiency was troubling. Two studies associating pandemic H1N1 with immune deficiency is alarming. If pandemic 2009 H1N1 is capable of causing long term immune deficiency, the implications are staggering. So, also, may be the ultimate death toll.
Lichtner, et al. (2010) Blood Circulating Dendritic Cells, Are Important Effectors Of Immune System, Are Impaired In Patients With H1n1 Flu Pneumonia: A Cause Or A Consequence Of The Disease? Interscience Conference on Antimicrobial Agents and Chemotherapy. Boston, MA. September 15, 2010.
Chehimi et al (2002) Persistent Decreases in Blood Plasmacytoid Dendritic Cell Number and Function Despite Effective Highly Active Antiretroviral Therapy and Increased Blood Myeloid Dendritic Cells in HIV-Infected Individuals. J. Immunol. 168: 4796-4801.