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Objective: To compare psychometric properties of Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Shoulder Pain and Disability Index (SPADI) and Constant–Murley scale, in patients with degenerative rotator cuff disease (DRCD). Design: Longitudinal cohort. Setting: One French university hospital. Methods: The scales were applied twice at one-week interval before physiotherapy and once after physiotherapy two months later. The perceived improvement after treatment was self-assessed on a numerical scale (0–4). The test–retest reliability of the DASH, SPADI and Constant–Murley scales was assessed before treatment by the intraclass correlation coefficient (ICC). The responsiveness was assessed by the paired t-test (P < 0.05) and standardized mean difference (SMD). The correlation between the percentage of variation in scale scores and the self-assessed improvement score after treatment was measured by the Spearman coefficient. Results: Fifty-three patients were included. Twenty-six only were available for reliability. The test–retest reliability was very good for the DASH (ICC = 0.97), SPADI (0.95) and Constant–Murley (0.92). The scale score was improved after treatment for each scale (P < 0.05). The SMD was moderate for the DASH (0.56) and SPADI (0.56) scales, and small for the Constant–Murley (0.44). The correlation between the percentage of variation in scores and self-assessed improvement score after treatment was high, moderate and not significant for the SPADI (0.59, P < 0.0001), DASH (0.42, P < 0.01) and Constant–Murley scales, respectively. Conclusion: The test–retest reliability of the DASH, SPADI and Constant–Murley scales is very good for patients with DRCD. The highest responsiveness was achieved with the SPADI. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether frequency of rheumatoid arthritis (RA) and/or other autoimmune (AI) disorders was increased in RA French Caucasian families among the first- (FDR) and second-degree relatives (SDR), and to test whether the presence of AI disease family history identified a specific RA subset., Methods: We conducted telephone interviews to obtain histories of AI diseases among the FDR and SDR of 368 RA probands, belonging either to trio or affected sib-pair (ASP) families. All the AI diagnoses were confirmed by the physician of the affected relative., Results: Probands of the ASP families were characterized by older age at RA onset, longer disease duration, and larger family size versus trio families. In the trio families, the prevalence of AI diseases was 6.05% (4.76%-7.57%) in FDR and 2.40% (1.85%-3.06%) in SDR. In ASP families, the prevalence of AI diseases was, respectively, 10.24% (8.68%-11.97%) and 1.79% (1.41%-2.25%). The most frequent AI diseases among relatives were RA, thyroid AI diseases, and vitiligo. In trio families, a proband with a mean age of RA onset < 30 years was associated with AI disease prevalence in the relatives, and male gender was associated with prevalence of RA among the FDR., Conclusion: The prevalence of AI diseases is increased, particularly among FDR, in French RA families, and some characteristics of the RA proband seem to be associated with prevalence of AI diseases in families.

We study the association between three protein kinase C, eta gene polymorphisms (+8134C/T, rs912620, rs959728), and susceptibility to rheumatoid arthritis. One hundred French Caucasian rheumatoid arthritis trio families were genotyped. Relative quantification of protein kinase C, eta mRNA expression was performed from whole blood in 24 unrelated rheumatoid arthritis patients and in 16 healthy controls. Our results showed no significant association or linkage between the protein kinase C, eta polymorphisms, and rheumatoid arthritis. The protein kinase C, eta mRNA was expressed at lower level in rheumatoid arthritis unrelated patients than in healthy controls. This study shows that protein kinase C, eta gene is not a Rheumatoid Arthritis major susceptibility genetic factor in the French Caucasian population. Furthermore, the lower expression of this gene in rheumatoid arthritis patients comparing to healthy controls suggests that protein kinase C, eta could be associated with the patho-physiologic mechanism of rheumatoid arthritis.

Recently, we proposed a classification of HLA-DRB1 alleles that reshapes the shared epitope hypothesis in rheumatoid arthritis (RA); according to this model, RA is associated with the RAA shared epitope sequence (72-74 positions) and the association is modulated by the amino acids at positions 70 and 71, resulting in six genotypes with different RA risks. This was the first model to take into account the association between the HLA-DRB1 gene and RA, and linkage data for that gene. In the present study we tested this classification for validity in an independent sample. A new sample of the same size and population (100 RA French Caucasian families) was genotyped for the HLA-DRB1 gene. The alleles were grouped as proposed in the new classification: S1 alleles for the sequences A-RAA or E-RAA; S2 for Q or D-K-RAA; S3D for D-R-RAA; S3P for Q or R-R-RAA; and X alleles for no RAA sequence. Transmission of the alleles was investigated. Genotype odds ratio (OR) calculations were performed through conditional logistic regression, and we tested the homogeneity of these ORs with those of the 100 first trio families (one case and both parents) previously reported. As previously observed, the S2 and S3P alleles were significantly over-transmitted and the S1, S3D and X alleles were under-transmitted. The latter were grouped as L alleles, resulting in the same three-allele classification. The risk hierarchy of the six derived genotypes was the same: (by decreasing OR and with L/L being the reference genotype) S2/S3P, S2/S2, S3P/S3P, S2/L and S3P/L. The homogeneity test between the ORs of the initial and the replication samples revealed no significant differences. The new classification was therefore considered validated, and both samples were pooled to provide improved estimates of RA risk genotypes from the highest (S2/S3P [OR 22.2, 95% confidence interval 9.9-49.7]) to the lowest (S3P/L [OR 4.4, 95% confidence interval 2.3-8.4]).

The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes for lymphoid tyrosine phosphatase LYP, involved in the negative regulation of early T-cell activation. An association has recently been reported between the PTPN22-620W functional allele and rheumatoid factor-positive (RF+) rheumatoid arthritis (RA), among other autoimmune diseases. Expected linkage proof for consistency cannot be definitely produced by an affected sib-pair (ASP) analysis. Our aim was therefore to search for linkage evidence with the transmission disequilibrium test. DNA from the French Caucasian population was available for two samples of 100 families with one RA patient and both parents, and for 88 RA index cases from RA ASP families. Genotyping was carried out by PCR-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, genotype relative risk and ASP-based analysis. The transmission disequilibrium test of the PTPN22-620W allele revealed linkage and association for RF+ RA (61% of transmission, P = 0.037). The genotype relative risk showed the risk allele in 34% of RF+ RA patients and in 24% of controls derived from nontransmitted parental chromosomes (P = 0.047, odds ratio = 1.69, 95% confidence interval = 1.03-2.78). The ASP investigation showed no enriched risk allele in RA multiplex families, resulting in a lack of power of ASP analysis, explaining the published negative results. This study is the first to show linkage of PTPN22 to RF+ RA, consistent with PTPN22 as a new RA gene.

Objective: Results of genome scans in rheumatoid arthritis (RA) have suggested that the tumor necrosis factor receptor I (TNFRI) and TNFRII loci (TNFR1 and TNFR2) are susceptibility loci. A TNFR2 polymorphism was found to be associated with familial RA. TNFR1 is mutated in TNFR-associated periodic syndrome (TRAPS). We undertook this study to test the TNFR1 exonic polymorphism closest to the TRAPS mutations site (+36 A/G) for association with RA., Methods: DNA samples were available from two groups of the French Caucasian population: 1) 100 families with 1 RA patient and both parents and 2) 86 RA index patients from families with at least 2 siblings with RA (affected sibpairs [ASPs]). The +36 A/G polymorphism of TNFR1 was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The analysis was performed using the transmission disequilibrium test, the genotype relative risk, and a linkage-based test previously described., Results: A negative association between RA and the +36 A/A genotype, suggested in the first sample (P = 0.084), was demonstrated in the second (ASP RA) sample (odds ratio [OR] 0.465; P = 0.012) and confirmed by the linkage-based test (OR 0.17; P = 0.008). The protective genotype, present in 41% of controls, was less frequent in RA patients: 33% in the first sample, 24% in the ASP RA sample, and 11% in the linkage-derived subgroup. Distribution of both TNFR2 196 R/R and TNFR1 +36 A/A genotypes in the ASP RA sample showed that both suspected genotypes were exclusive., Conclusion: We found evidence for an association between RA and a TNFR1 protective genotype, restricted to familial RA. Distribution of the TNFR2 196 R/R and TNFR1 +36 A/A genotypes in familial RA could suggest an interaction between TNFR1 and TNFR2 in the genetic susceptibility for RA.