Arthro-distension with early and intensive mobilization for shoulder adhesive capsulitis: A randomized controlled trial.

BACKGROUND: There are several therapeutic options for the management of shoulder adhesive capsulitis (AC). The superiority of arthro-distension over intra-articular steroid injection (ISI) for AC remains controversial. OBJECTIVES: To evaluate the efficacy of a single arthro-distension procedure combined with early and intensive mobilization (ADM) and physiotherapy, versus ISI and physiotherapy, in people with AC lasting ≥3 months. METHODS: This was a prospective, 2 parallel-group, 2-center, observer-blind randomized controlled trial conducted in tertiary care settings. Adults with AC were randomly assigned to the treatment or control group. Efficacy was assessed using the self-administered Shoulder Pain and Disability Index (SPADI). Total, pain and disability SPADI scores 15 days, 6 weeks, and 3, 6 and 12 months after the procedure (total SPADI at 15 days: primary outcome; other outcomes were secondary) were compared between groups using analysis of covariance (ANCOVA). A post hoc analysis stratified on the initial range of passive glenohumeral abduction, which had not been pre-specified, was conducted. RESULTS: There were 33 participants in each group. Both groups improved over time. Mean (SD) total SPADI score at 15 days was 33.8 (19.6) in the treatment group and 32.8 (17.5) in the control group, p = 0.393. There were no significant differences for any variables in the overall sample. The post hoc analysis found ADM to be associated with a significant decrease in total SPADI score at 15 days compared with ISI (p = 0.049) in individuals with initial passive glenohumeral abduction >45°. CONCLUSIONS: The effects of ADM on pain and function were not statistically different from those of ISI. However, ADM may be useful in individuals with initial passive glenohumeral abduction >45°. DATABASE REGISTRATION: NCT00724113.

Value of a clinical test of sub-acromial impingement to predict response to physiotherapy with dynamic humeral centering: A preliminary study.

BACKGROUND: Dynamic humeral centering (DHC) is a physiotherapy modality that aims to prevent sub-acromial impingement of rotator cuff tendons. We recently developed a new clinical manoeuver - the Viggo-Cochin test - to enhance the ability of the Neer test to detect sub-acromial impingement. Here we hypothesised whether the DHC effect may differ between individuals with positive and negative Viggo-Cochin test results. OBJECTIVE: To assess the association between DHC and Viggo-Cochin test results. METHODS: Individuals with shoulder pain due to sub-acromial impingement underwent the Neer and Viggo-Cochin tests at baseline. They were assessed before and after DHC by the Shoulder Pain and Disability Index (SPADI). A positive response to DHC was defined as a 20% reduction in the SPADI. RESULTS: We included 50 individuals (53 shoulders). The response to DHC did not differ by Neer test result at baseline: OR 0.73 [95% CI 0.22-2.38] (p= 0.601). By contrast, the response to DHC was 5-fold higher with a positive than negative Viggo-Cochin test result: OR 5.11 [95% CI 1.47-17.78] (p= 0.010). CONCLUSIONS: We found a higher clinical response to DHC with a positive than negative Viggo-Cochin test result at baseline in individuals with shoulder pain due to rotator cuff disease.

Shoulder adhesive capsulitis: diagnostic value of active and passive range of motion with volume of gleno-humeral capsule as a reference.

BACKGROUND: The diagnosis of adhesive capsulitis is currently based on restricted range of motion (ROM) but its diagnostic value has only been rarely investigated. AIM: The aim of this study is to assess the diagnostic value of active global and passive gleno-humeral ROM to diagnose shoulder adhesive capsulitis. DESIGN: Cross-sectional descriptive study. SETTING: One French center for Rehabilitation Medicine. POPULATION: Patients referred for treatment of shoulder adhesive capsulitis in our center were included. Inclusion criteria were: shoulder pain; limitation of active global ROM (abduction or flexion <180°); limitation of passive gleno-humeral ROM (abduction or flexion <90° or 25% reduction at less of lateral rotation versus the opposite shoulder); no gleno-humeral arthropathy on radiography. METHODS: The volume of the gleno-humeral capsule was assessed during a procedure of arthro-distension. The reference criterion for adhesive capsulitis was a volume <12 mL. We analyzed the correlation between the parameters of mobility and the volume of the gleno-humeral capsule; and the positive predictive value (PPV) of inclusion criteria, with the reference criterion for the diagnosis of adhesive capsulitis. RESULTS: We included 38 patients. Passive gleno-humeral ROM in abduction only was correlated with volume of the gleno-humeral capsule: r=0.33, P=0.043. The PPV of inclusion criteria was 82% for the diagnosis of shoulder adhesive capsulitis. Rather than 90°, when we considered 80°, 60° and 40° as the threshold of passive gleno-humeral ROM in abduction, the PPV increased from 83% to 100%. CONCLUSIONS: Passive gleno-humeral ROM in abduction is correlated with volume of the gleno-humeral capsule. The PPV is high for active global and passive gleno-humeral ROM for diagnosis of shoulder adhesive capsulitis. CLINICAL REHABILITATION IMPACT: Limitation of active and passive shoulder ROM, especially passive abduction gleno-humeral, is a good criterion to diagnose shoulder adhesive capsulitis, in patients with shoulder pain and no gleno-humeral arthropathy on radiography.

Comparative study of psychometric properties of three assessment tools for degenerative rotator cuff disease.

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.

Reproducibility of sub-acromial impingement tests, including a new clinical manoeuver.

BACKGROUND: The Neer, Hawkins, and Yocum clinical tests detect sub-acromial impingement as a pathogenic process of degenerative rotator cuff disease. Their reproducibility has been little investigated. OBJECTIVES: We tested the reproducibility of the Neer, Hawkins, and Yocum clinical tests for detecting this sub-acromial impingement and also an original clinical manoeuver, the countertest with elevation with lateral rotation (CELR), which is a test of sub-acromial impingement. METHODS: Patients with shoulder pain due to degenerative rotator cuff disease were prospectively included. They were assessed with the Neer, Hawkins and Yocum tests as well as the CELR twice at a 1 week interval. Intra- and inter-observer reproducibility was assessed by percentage agreement and the kappa coefficient of concordance with 95% confidence intervals (CIs). Concordance was poor with kappa ≤0.4, moderate >0.4, and good >0.61. It was considered suitable for clinical use with kappa >0.4. RESULTS: We included 34 patients (mean [SD] age 60 [11] years; 26 females). For intra-observer reproducibility, agreement was 80% to 88%. By the kappa coefficient, intra-observer reproducibility was poor for the Neer test and moderate for the Hawkins test (0.56 [95% CI 0;0.9]) and Yocum test (0.48 [0;0.8]) and CELR (0.6 [0.2;0.9]). For inter-observer reproducibility, agreement was 73% to 88%. By the kappa coefficient, inter-observer reproducibility was poor for the Yocum test, moderate for the Hawkins test (0.54 [0.2;0.8]) and CELR (0.58 [0.2;0.8]), and good for the Neer test (0.64 [0.2;0.9]). CONCLUSION: The Hawkins test and CELR had a balanced profile of reproducibility suitable for clinical practice. We underline the potential interest of CELR, an original manoeuver.

Efficacy of dynamic humeral centering according to Neer test results: a stratified analysis of a randomized-controlled trial.

The aim of this study was to assess the efficacy of dynamic humeral centering (DHC) according to Neer test results. The study was a stratified analysis of a previously reported randomized trial. The patients included had shoulder pain with impingement syndrome. Interventions were DHC or nonspecific mobilization for control. The primary outcome was the Constant score including subscores for pain, activity, mobility, and strength at 3 months. All patients improved at follow-up, with better results after DHC. There was no interaction between Neer test results, treatments, and time. However, a trend toward higher effect sizes was observed after DHC in patients with a positive Neer test in comparison with negative patients. Patients with a positive Neer test showed improvement after DHC for rotator cuff disease compared with nonspecific mobilization.

Effect of dynamic humeral centring (DHC) treatment on painful active elevation of the arm in subacromial impingement syndrome. Secondary analysis of data from an RCT.

BACKGROUND: The physiotherapy dynamic humeral centring (DHC) aims to prevent subacromial impingement of rotator cuff tendons during elevation of the arm. The objective of the study was to determine whether DHC acts via an effect on subacromial impingement mechanism by assessing its effect on painful elevation of the arm in subacromial impingement syndrome. METHODS: This is a secondary analysis of results of a randomised controlled trial of the effectiveness of DHC. Sixty-nine patients with subacromial impingement syndrome were prospectively included. Patients and the assessor were blinded to the study hypothesis and treatment, respectively. Patients underwent DHC or non-specific mobilisation as a control for 6 weeks in 15 supervised individual outpatient sessions with home exercises. Outcomes were pain-free range of motion and presence of painful arc of the shoulder, both in active flexion and abduction of the arm at 3 months. RESULTS: At 3 months, pain-free range of motion, both flexion and abduction, was greater in the DHC group than in the mobilisation group. The number of patients with painful arc during flexion was decreased in the DHC group. CONCLUSIONS: DHC improves painful active elevation of the arm. We suggest that DHC may act via a specific effect on subacromial impingement mechanism.

URAM scale for functional assessment in Dupuytren's disease: a comparative study of its properties.

OBJECTIVE: To test the convergent validity and ease of use of the Unité Rhumatologique des Affections de la Main (URAM) scale for patients with Dupuytren's disease. METHODS: Patients were prospectively included. We compared the convergent validity of the URAM scale, the Cochin Hand Function Scale (CHFS) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, in terms of their correlation with the Tubiana score and self-assessed disability on a visual analog scale (VAS). Pearson's correlation was used for the convergent validity study. The response time for questionnaire completion was the outcome for ease of implementation. RESULTS: We included 53 patients with Dupuytren's disease in the convergent validity study and 30 other patients with the disease in the time-response assessment. The URAM scale showed strong convergence with the Tubiana scale (r=0.64) and self-assessed disability on a VAS (r=0.69). Convergence with the Tubiana and self-assessed disability was higher for the URAM scale than the CHFS or DASH questionnaire. The mean [SD] response time was shorter for the URAM scale than the CHFS or DASH questionnaire (42 [20] vs 71 [35] and 103 [59] s, respectively, P<0.0001). CONCLUSIONS: The results reinforce the psychometric merits of the URAM scale. Furthermore, the response time for assessing disability was shorter with the URAM scale than the CHFS or DASH questionnaire. This evidence supports the high recommendation for the use of the URAM scale in clinical practice and clinical studies to assess disability in Dupuytren's disease.

Unité Rhumatologique des Affections de la Main (URAM) scale: development and validation of a tool to assess Dupuytren's disease-specific disability.

OBJECTIVE: To our knowledge, no functional outcome measure has been developed and validated for Dupuytren's disease. We aimed to develop and validate a patient-reported functional outcome measure for Dupuytren's disease. METHODS: Patients with Dupuytren's disease (n = 9) and medical experts (n = 7) provided input and opinions about limiting activities that were difficult to perform because of Dupuytren's disease for item generation. The provisional scale was studied in an independent sample of patients (n = 85) for item reduction according to response distribution, reliability, redundancy, and loading in a 1-factor solution. The final scale was evaluated as follows: reliability using Cronbach's alpha coefficient and test-retest intraclass correlation coefficient from the previous 85-patient population, and construct validity and responsiveness after needle aponeurotomy in another independent 53-patient sample. For construct validity, convergent validity and divergent validity were tested. The clinically important change was estimated relative to a 1-point categorical change on the Tubiana scale. RESULTS: A 52-item provisional scale was generated and reduced to the final 9-item scale called the Unité Rhumatologique des Affections de la Main (URAM) scale (total score 0-45). The scale showed good to excellent reliability and suitable construct validity. The URAM score improved after needle aponeurotomy: the standardized effect size was 0.56. The estimated clinically important change of the URAM scale was 2.9 points. CONCLUSION: We provide the first patient-reported functional measure for Dupuytren's disease. The URAM scale demonstrated suitable psychometric properties, and is short and convenient enough for easy use in daily practice and in clinical studies.

Assessment of dynamic humeral centering in shoulder pain with impingement syndrome: a randomised clinical trial.

OBJECTIVES: Treatment for degenerative rotator cuff disease of the shoulder includes physiotherapy. Dynamic humeral centering (DHC) aims at preventing subacromial impingement, which contributes to the disease. The goal of this study was to assess the effectiveness of DHC. METHOD: 69 patients with shoulder pain and impingement syndrome were prospectively included in a single-centre randomised trial with a 12-month follow-up. Patients and assessor were blinded to the study hypothesis and treatment, respectively. DHC and non-specific mobilisation as control were performed for 6 weeks, in 15 supervised individual outpatient sessions, and patients performed daily home exercises. The planned primary outcome was the Constant score including subscores for pain, activity, mobility and strength at 3 months. Secondary outcomes were the Constant score and subscores at 12 months, and medication use for pain at 3 and 12 months. RESULTS: The DHC group did not differ from the control group in the total Constant score at 3 months. However, the DHC group showed a higher Constant subscore for pain (12.2 (SD 2.8) vs 9.9 (2.9), least square means difference 2.1, 95% CI 0.7 to 3.5, p=0.004). At 3 months, the DHC group also showed a higher rate of no medication use (96.7% vs 71%, proportional difference 25.7, 95% CI 3.7 to 51.9, p=0.012). There was no other intergroup difference. CONCLUSIONS: There was no difference in the total Constant score between DHC and controls. However, pain was improved at 3 months after DHC. The differences found in subscores for pain should be explored in future studies. Trial registration clinicaltrials.gov Identifier: NCT 01022775.

Multi-needle aponeurotomy for advanced Dupuytren's disease: preliminary results of safety and efficacy (MNA 1 study).

AIM: To assess the safety and efficacy of multi-needle aponeurotomy (MNA) for advanced Duputren's disease. METHODS: This prospective study included patients with age more than 17 years, Dupuytren's contracture with palmo-digital or poly-digital involvement, presumed NA number needed to treat>4, and availability for at least 1-month follow-up after MNA. Outcome measures were Tubiana score and passive extension deficit, after MNA and at 1 and 6 months; self-assessed disability and satisfaction at 1 and 6 months; and adverse events (AEs). RESULTS: Thirty patients were included. MNA was performed on 37 hands and 99 rays. Among 25 assessed MNA sessions for treatment-related discomfort, patients considered 22 (88%) not at all to moderately painful. Six minor AEs, representing 2 for every 100 NAs, were reported. Tubiana scores at baseline (5.3±2.3, n=35) were improved after treatment (1.7±1.8, n=32, P<0.0001), at 1 month (2.2±1.4, n=26, P<0.0001) and at 6 months (2.8±2.7, n=19, P<0.01). Passive extension deficit was greatly reduced after treatment and persisted at follow-up. Disability scores at baseline (27.6±26.9, n=37) were reduced at 1 month (13.2±19.5, n=26, P=0.02) and at 6 months (5.2±11.6, n=20, P<0.001). Patients were highly satisfied at 1 month (100%, n=25) and 6 months (95%, n=19). CONCLUSION: MNA appears safe and effective for advanced Dupuytren's disease. It could become a treatment of reference and contribute to reducing the need for surgery in this indication.

Mutations of the cystic fibrosis gene in patients with bronchiectasis associated with rheumatoid arthritis.

OBJECTIVES: In cystic fibrosis, mutations of the CFTR gene lead to diffuse bronchiectasis (DB). DB is also associated with other diseases including rheumatoid arthritis (RA) in which the role of genetic factors in the predisposition to DB remains unclear. METHODS: A family-based association study was carried out to determine whether the frequency of CFTR mutations was higher in patients with RA-associated DB and to determine whether a causal relationship could be established between the variant and the disease by evaluating its cosegregation with DB within families. Families of probands with RA-DB were included if one first-degree relative had RA and/or DB. The controls comprised healthy subjects requesting genetic counselling because their partner had cystic fibrosis. RESULTS: The frequency of CFTR mutations was higher in family members with RA-DB or DB only than in unaffected relatives (p<0.005 for each comparison) and in unrelated healthy controls (p<0.001 for each comparison) but not in family members with RA only. CFTR mutations were more frequent in family members with RA-DB than in those with RA only (OR 5.30, 95% CI 2.48 to 11.33; p<5×10(-5)). They cosegregated with RA-DB in the families (sib-TDT=10.82, p=0.005). CONCLUSIONS: RA-DB should be added to the list of phenotypes in which CFTR mutations are pathogenic. CFTR mutation is the first genetic defect linked to an extra-articular feature of RA to be described. CFTR mutations in patients with RA appear to be an important marker of the risk of associated DB, which has been linked to a less favourable prognosis.

Efficacy of a functional restoration program for chronic low back pain: prospective 1-year study.

OBJECTIVE: To evaluate the efficacy of a functional restoration program for patients with chronic low back pain, using overall disability and work ability as the primary evaluation criteria. PATIENTS AND METHODS: We prospectively studied patients aged 18 years or older who had been on sick leave because of nonspecific low back pain for at least 3 months and whose job position was still open. The program was delivered on a day-hospital basis 5 days a week for 5 weeks. Patients were followed up for 1 year. RESULTS: We included 39 patients, 11 females and 28 males with a mean (± SD) age of 43 ± 8 years and a mean sick-leave duration of 10 ± 7 months. After 1 year, 26 (67%) patients reported improvements and 25 (64%) had returned to work. Compared to the year before the program, the number of sick leave days was decreased by 51% (120 ± 140 vs. 244 ± 114, P < 0.05). The work-and-leisure-activities subscore of the validated French version of the Dallas Pain Questionnaire (DRAD) was significantly improved (57 ± 24 vs. 70 ± 17 at baseline, P < 0.05). The patients still on sick leave after 1 year were older and had greater alterations in baseline DRAD subscores for anxiety/depression and daily activities, compared to the patients who had returned to work. CONCLUSIONS: Our functional restoration program was effective and allowed two-thirds of patients to resume work. Factors associated with failure to resume work were well-known correlates of chronicity. Our results support the use of functional restoration programs in patients with incapacitating low back pain. They suggest that functional restoration may deserve to be started earlier, after only 3 months with chronic pain, in patients who are unable to work.

Transcriptome analysis describing new immunity and defense genes in peripheral blood mononuclear cells of rheumatoid arthritis patients.

BACKGROUND: Large-scale gene expression profiling of peripheral blood mononuclear cells from Rheumatoid Arthritis (RA) patients could provide a molecular description that reflects the contribution of diverse cellular responses associated with this disease. The aim of our study was to identify peripheral blood gene expression profiles for RA patients, using Illumina technology, to gain insights into RA molecular mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: The Illumina Human-6v2 Expression BeadChips were used for a complete genome-wide transcript profiling of peripheral blood mononuclear cells (PBMCs) from 18 RA patients and 15 controls. Differential analysis per gene was performed with one-way analysis of variance (ANOVA) and P values were adjusted to control the False Discovery Rate (FDR<5%). Genes differentially expressed at significant level between patients and controls were analyzed using Gene Ontology (GO) in the PANTHER database to identify biological processes. A differentially expression of 339 Reference Sequence genes (238 down-regulated and 101 up-regulated) between the two groups was observed. We identified a remarkably elevated expression of a spectrum of genes involved in Immunity and Defense in PBMCs of RA patients compared to controls. This result is confirmed by GO analysis, suggesting that these genes could be activated systemically in RA. No significant down-regulated ontology groups were found. Microarray data were validated by real time PCR in a set of nine genes showing a high degree of correlation. CONCLUSIONS/SIGNIFICANCE: Our study highlighted several new genes that could contribute in the identification of innovative clinical biomarkers for diagnostic procedures and therapeutic interventions.

Genetic and expression analysis of CASP7 gene in a European Caucasian population with rheumatoid arthritis.

OBJECTIVE: To study the possible role of the caspase 7 (CASP7) gene in susceptibility to rheumatoid arthritis (RA) in a European Caucasian population. METHODS: CASP7 rs2227309 single nucleotide polymorphism (SNP) was genotyped in 197 French RA trio families and in 252 European RA families available for replication using Taqman allelic discrimination assay. Relative quantification of caspase 7 isoforms alpha and beta mRNA expression was performed from whole blood in 25 unrelated patients with RA and in 15 healthy controls by real-time quantitative reverse transcription-polymerase chain reaction. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies, the transmission disequilibrium test, and the genotype relative risk. RESULTS: We observed, in the first sample, a significant association of rs2227309-AA genotype with RA [p=0.03, odds ratio (OR) 2.11 (95% CI 1.0-4.6)]. The second sample did not show any significant association of the AA genotype with RA [p=0.6, OR 0.87 (95% CI 0.4-1.8)]. When the 2 samples were combined, no significant association of the AA genotype [p=0.3, OR 1.32 (95% CI 0.8-2.2)] was observed. CASP7 isoforms alpha and beta mRNA were expressed in patients with RA at lower level than in healthy controls (-89%, p=0.003 and -47%, p=0.01; respectively). CONCLUSION: CASP7 rs2227309 SNP was not associated with RA in a European Caucasian population. Nevertheless, CASP7 isoforms alpha and beta could have an involvement in the apoptosis process in RA.

Prevalence and distribution of autoimmune diseases in 368 rheumatoid arthritis families.

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.

Association and expression study of PRKCH gene in a French Caucasian population with rheumatoid arthritis.

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.

The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study.

The integrin alpha(v)beta3, whose alpha(v) subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus 50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3-2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene.

Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene.

The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of approximately 5% on average and large variations of population allele frequencies (2.1-15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22-1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 "trio" families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P < 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2-2.8)]. In conclusion, we provided the linkage proof for the PTPN22-1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a "linkage-proven" autoimmunity gene. PTPN22 accounting for approximately 1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.

IRF5 rs2004640-T allele, the new genetic factor for systemic lupus erythematosus, is not associated with rheumatoid arthritis.

BACKGROUND: Recently, a new genetic factor within the interferon regulatory factor 5 (IRF5) gene was demonstrated for systemic lupus erythematosus (SLE) through linkage and association: the rs2004640-T allele. IRF5 is involved in the production of rheumatoid arthritis (RA) cytokines, and SLE already shares with RA one genetic factor within the tyrosine phosphatase PTPN22 gene. AIM: To test the hypothesis that the SLE IRF5 genetic factor could also be shared with RA. PATIENTS AND METHODS: 100 French Caucasian trio families with RA were genotyped and analysed with the transmission disequilibrium test, the frequency comparison of the transmitted and untransmitted alleles, and the genotype relative risk. 97% power was available to detect at least a trend in favour of a factor similar to that reported for SLE. RESULTS: The analysis showed the absence of linkage and association globally and in "autoimmune" RA subsets, with a weak non-significant trend against the IRF5 rs20046470-T allele. Given the robustness of familial-based analysis, this slight negative trend provided strong evidence against even a weaker factor than that reported for SLE. CONCLUSION: Our results exclude the IRF5 rs2004640-T allele as a major genetic factor for RA in this French Caucasian population.