title: Polymorphisms of Toll-like receptor-4 and CD14 in systemic lupus erythematosus and rheumatoid arthritis.
abstract: BACKGROUND
  Toll-like receptor 4 (TLR4) and its co-receptor CD14 play a major role in innate immunity by recognizing PAMPs and signal the activation of adaptive responses. These receptors can recognize endogenous ligands mainly auto-antigens. In addition, TLR4 (Asp299Gly) and CD14 (C/T -159) polymorphisms (SNPs) may modify qualitatively and/or quantitatively their expression. Therefore, they could be implied in autoimmune diseases and can influence both susceptibility and severity of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).
  
  
  METHODS
  TLR4 (Asp299Gly) and CD14 (C/T -159) SNPs were genotyped using polymerase chain reaction (PCR)-RFLP in 127 SLE patients, 100 RA patients, and 114 healthy controls matched in age and gender.
  
  
  RESULTS
  CD14*T allele was significantly more frequent in SLE patients (0.456) comparatively to controls (0.355), p = 0.02 OR (95% CI) = 1.53 [1.04-2.24]. In RA patients, the higher frequency of CD14*T allele (0.405) failed to reach significance, p = 0.28. Investigation of the TLR4 (Asp299Gly) SNP showed no significant association neither with SLE nor with RA.Analysis of these SNPs according to clinical and biological features showed a significant higher frequency of arthritis in SLE patients carrying CD14*T/T genotype (92%) comparatively to those with C/C and C/T genotypes (72.5%), p = 0.04. Moreover, SLE patients carrying CD14*T/T/TLR4*A/A haplotype had significantly more arthritis (91.3%) than the rest of SLE group (73%), p = 0,044 and confirmed by multivariable analysis after adjustment according to age and gender, p = 0.01.
  
  
  CONCLUSIONS
  The CD14 (-159)*T allele seems to be associated with susceptibility to SLE and arthritis occurrence.
authors.affiliation: Laboratory of Research in Immunology of Renal Transplantation and Immunopathology (LR03SP01) Charles Nicolle Hospital, Tunis El Manar University, Bd 9 Avril, 1006 Bab Saadoun, Tunis, Tunisia. gorgi.yousr@gmail.com.
authors.forename: Tarak
authors.initials: T
authors.lastname: Dhaouadi
authors.forename: Imen
authors.initials: I
authors.lastname: Sfar
authors.forename: Youssra
authors.initials: Y
authors.lastname: Haouami
authors.forename: Leila
authors.initials: L
authors.lastname: Abdelmoula
authors.forename: Sami
authors.initials: S
authors.lastname: Turki
authors.forename: Lamia Ben
authors.initials: LB
authors.lastname: Hassine
authors.forename: Rafik
authors.initials: R
authors.lastname: Zouari
authors.forename: Adel
authors.initials: A
authors.lastname: Khedher
authors.forename: Narjess
authors.initials: N
authors.lastname: Khalfallah
authors.forename: Taieb Ben
authors.initials: TB
authors.lastname: Abdallah
authors.forename: Yousr
authors.initials: Y
authors.lastname: Gorgi