Rheumatoid Arthritis: Gandjbakhch F

Gandjbakhch F, Fajardy I, Ferré B, Dubucquoi S, Flipo RM, Roger N, Solau-Gervais E. · Department of Rheumatology, Lille University Hospital, Lille, France. · J Rheumatol. · Pubmed #19332633 No free full text.

Abstract: OBJECTIVE: A functional haplotype of peptidyl arginine deiminase 4 (PADI4) was associated with susceptibility to rheumatoid arthritis (RA) in Asian populations, but the results are contradictory in Europeans. We investigated (1) the association of 2 single-nucleotide polymorphisms (SNP) located in exon 2 of PADI4 with RA in another Caucasian population; and (2) the association between PADI4 and anti-citrullinated protein (anti-CCP) antibodies. METHODS: DNA samples were obtained from 405 French RA patients and 275 controls. All RA patients met the revised criteria of the American College of Rheumatology. PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP were genotyped using a PCR-RFLP method confirmed by direct sequencing. All patients and controls were genotyped for HLA-DRB1. The presence of anti-CCP antibodies was tested in 243 RA patients using an ELISA technique. RESULTS: We focused on PADI4_89 163(G-->A) and PADI4_90 245(T-->C) SNP that distinguished 2 main haplotypes: AC haplotype (PADI4_89*A PADI4_90*C) and GT haplotype (PADI4_89*G PADI4_90*T), described, respectively, as "nonsusceptible" and "susceptible." A positive association between RA and presence of the GT haplotype was found in the heterozygous state (p = 0.002) and the homozygous state (RA patients 22%, controls 13%; p = 0.005). A correlation was observed between the presence but not the level of anti-CCP antibodies and the GT heterozygous (p = 0.03) and homozygous (p = 0.05) haplotypes. No correlation was found between the HLA-DRB1 shared epitope and any of the PADI4 haplotypes. CONCLUSION: Our findings confirm those of Japanese, Korean, and Canadian studies and suggest that PADI4 may be a new susceptibility gene independent of HLA-DRB1 for RA in Caucasian populations.

Karie S, Gandjbakhch F, Janus N, Launay-Vacher V, Rozenberg S, Mai Ba CU, Bourgeois P, Deray G. · Department of Nephrology, Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'hôpital, 75013 Paris, France. · Rheumatology (Oxford). · Pubmed #18238787 No free full text.

Abstract: OBJECTIVES: The prevalence of kidney disease (KD) indicators together with the profile of RA drugs prescribed in RA patients was investigated in the MATRIX study (MeThotreXate And Renal Insufficiency). METHODS: Renal function (RF) was assessed using Cockcroft-Gault (CG) and abbreviated Modification of Diet in Renal Disease (aMDRD) study formulae. RESULTS: Serum creatinine (SCr) was normal in 81.4% of the 129 patients included. According to the National Kidney Foundation (NKF) classification, the distribution by stage of KD was, using the aMDRD and CG formulae, as follows: stage 1: 11.3% and 11.4%; stage 2: 20.0% and 20.3%; stage 3: 15.0% and 24.1%; stage 4: 0% and 1.3%; stage 5: 0%. Proteinuria, haematuria and leucocyturia were observed in 16%, 17% and 20% of the patients, respectively. Using the aMDRD and CG formulae, 36% and 38% of the prescriptions made in patients with glomerular filtration rate (GFR) <60 ml/min required a dosage adjustment. Among the patients with GFR <60 ml/min, 83-90% received at least one drug that required a dosage adjustment and 67-70% received at least one drug that was potentially nephrotoxic, according to aMDRD or CG formulae, respectively. Five (50%) and 8 (47%) patients did not have appropriate MTX dosage adjustment according to their stage of KD with aMDRD or CG formulae, respectively. CONCLUSION: Systematic estimation of RF with CG or aMDRD formulae and urine dipstick are necessary in RA patients. In patients with KD at high risk for drug toxicity, dosage should be adapted to RF.