The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility. We carried out a case–control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69–4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64–4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63–4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89–5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium. These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.

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A general method is described for enumerating antigen-sensitive lymphocytes obtained from individuals having delayed hypersensitivity, in this case from highly tuberculin-sensitive guinea pigs. The method is based on the observation that resting lymphocytes are generally unable to support replication of RNA viruses, whereas antigen-"activated" lymphocytes can. Lymph node lymphocytes from individual animals were cultured in the presence or absence of tuberculin purified protein derivatives (PPD). After various periods of time, the cells were infected either with Newcastle disease virus or vesicular stomatitis virus, and plated in agar over a monolayer of cells susceptible to the virus. Wherever a lymphocyte yielded infectious virus, a discrete plaque in the monolayer could be seen. The increase in plaques of the antigen-stimulated cells over the background of the control sample was taken as the number of antigen-sensitive cells in the population. When lymphocytes from normal guinea pigs or from guinea pigs immunized to produce only circulating antibody to PPD were similarly tested, no increase in plaque-forming units (PFU) was observed. The average increase in PFU due to antigenic stimulation varied from 1 per 1000 lymphocytes at 24 hr to 16 per 1000 lymphocytes at 96 hr. By employing inhibitors of mitosis (colchicine, vinblastine, and thymidine) it was evident that the increase in PFU at least up to 48 hr was primarily due to initial antigen-reactive cells and not their progeny.

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