Open AccessClinical and genetic risk factors for pneumonia in systemic lupus erythematosus
Author(s) -
Kinder Brent W.,
Freemer Michelle M.,
King Talmadge E.,
Lum Raymond F.,
Nititham Joanne,
Taylor Kim,
Edberg Jeffrey C.,
Bridges S. Louis,
Criswell Lindsey A.
Publication year - 2007
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.22804
Subject(s) - pneumonia , immunology , medicine , leukopenia , risk factor , odds ratio , haplotype , genotyping , genotype , biology , genetics , gene , chemotherapy
Objective To define the contribution of polymorphisms in genes encoding tumor necrosis factor ( TNF ), mannose‐binding lectin ( MBL ), and Fcγ receptor IIa ( FCGR2A ) as well as clinical factors, to the development of pneumonia in patients with systemic lupus erythematosus (SLE). Methods We studied 282 SLE patients from a multiethnic cohort. Pneumonia events and clinical risk factors for pneumonia were identified through medical record review. Genotyping was performed for MBL (+223, +230, and +239), TNF (–308, –238, and +488), and FCGR2A (–131H/R) polymorphisms. Univariate analyses were performed to identify clinical and genetic risk factors for pneumonia. Covariates for multivariate analysis included sex, ethnicity, treatment with immunomodulators, and leukopenia. Results Forty‐two patients (15%) had at least 1 episode of pneumonia. Polymorphism of the TNF gene, particularly the –238A allele and a related haplotype, revealed the most striking and consistent association with pneumonia in univariate analyses. Results of multivariate analyses indicated an odds ratio (OR) for the TNF –238A allele of 3.5 ( P = 0.007) and an OR for the related haplotype of 5.4 ( P = 0.001). Male sex, treatment with immunomodulators, and leukopenia also influenced the risk of pneumonia. Conclusion These findings suggest that specific TNF variants may identify SLE patients who are at particularly high risk of developing pneumonia. Given the prevalence and excessive morbidity associated with pneumonia in SLE, these findings have clinical relevance and provide insight into the pathogenesis.