Kate Johnson

September 19, 2014

WASHINGTON — Invasive pneumococcal disease in patients with no known risk factors may be linked to genetic susceptibility, according to a new study.

"These findings may — in the future — help us tailor care in invasive pneumococcal disease and help in prevention of the disease through vaccination," lead investigator Anna SanGil Betriu, MD, from the Hospital Universitari MútuaTerrassa in Terassa, Spain, told Medscape Medical News.

But although testing for the genes is possible in clinical practice, "it is very expensive, and we need more trials to confirm our results," she said.

Invasive pneumococcal disease is rare, occurring mostly in children and the elderly and only sporadically in middle-aged individuals, explained coinvestigator Esther Calbo Sebastián, MD, also from the Hospital Universitari MútuaTerrassa, who presented the study here at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

Known risk factors for the disease include coinfection with HIV, splenectomy, cancer, hepatic cirrhosis, and traumatic cerebrospinal fluid fistula.

Genetic factors such as primary immunodeficiencies, congential asplenia, complement deficiency, and antibody deficiency have been associated with risk for invasive pneumococcal disease, but the pathogenesis remains largely unknown. Evidence points to the involvement of many immunologic genes in susceptibility, said Dr. Calbo Sebastián.

The study investigated the influence of ten genes involved in the immunologic response that have previously been associated with risk for infection.

White patients (n = 153; mean age, 37 years; 42% women) who had been diagnosed with invasive pneumococcal disease at 6 hospitals were ethnically matched to 302 healthy control individuals (mean age, 60 years; 61% women).

Most patients had been diagnosed with pneumonia (96%), and a few with either meningitis (3%) or bacteremia only (1%). Known risk factors were absent in 31%.

Blood was drawn from participants at the beginning of the study.

Polymorphism NFKBIZ and ILIRI

Investigators found a significant association between risk of invasive pneumococcal disease and a polymorphism of the NFKBIZ gene (P = .02).

Additionally, there was a trend toward an association between risk for the disease and a polymorphism of the IL1R1 gene (P = .08), said Dr. Calbo.

When only patients without risk factors were compared with control persons, these associations were stronger (P = .01 and P = .05).

"Our data suggest that genetic polymorphisms in the IL1R1 and NFKBIZ genes may contribute to risk [of infection], and patients with no known risk factors have a higher load of invasive pneumococcal disease–associated mutations, which may explain their susceptibility," she concluded.

"Finding the genes and pathways involved in the susceptibility of complex traits, such as the one analyzed, is a major challenge nowadays," said Carlos Flores, PhD, a molecular geneticist from Hospital Universitario NS de Candelaria, Tenerife, Spain, who specializes in genetic susceptibility to infections, particularly sepsis and acute respiratory distress syndrome.

"Studies like this one constitute initial steps towards the identification of mechanisms underlying disease susceptibility, which will lead to improved diagnosis and to development of novel interventions," he told Medscape Medical News.

Dr. Betriu, Dr. Calbo, and Dr. Flores have disclosed no relevant financial relationships.

54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract B2002. Presented September 9, 2014.

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