Clinical and genetic risk factors for pneumonia in systemic lupus erythematosus.
OBJECTIVE
To define the contribution of polymorphisms in genes encoding tumor necrosis factor (TNF), mannose-binding lectin (MBL), and Fcgamma 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.


CONCLUSIONS
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.
Division of Rheumatology, University of California-San Francisco, 374 Parnassus Avenue, San Francisco, CA 94143, USA.
Brent W
BW
Kinder
Michelle M
MM
Freemer
Talmadge E
TE
King
Raymond F
RF
Lum
Joanne
J
Nititham
Kim
K
Taylor
Jeffrey C
JC
Edberg
S Louis
SL
Bridges
Lindsey A
LA
Criswell
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002140:California / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D011014:Pneumonia / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017452:Receptors, IgG / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C445323:FCGR2A protein, human; D037601:Mannose-Binding Lectin; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha