Relationship between growth hormone-IGF-I-IGFBP-3 axis and serum leptin levels with bone mass and body composition in patients with rheumatoid arthritis.

OBJECTIVES: Hormonal factors playing a role in bone mass and body composition have been rarely assessed in rheumatoid arthritis (RA). In this study, we aimed to evaluate the growth hormone (GH)-insulin-like growth factor-I (IGF-I)-insulin-like growth factor binding protein-3 (IGFPB-3) axis and serum leptin levels in patients with RA and to determine whether these hormonal/growth factors may influence bone mass and body composition in RA. METHODS: Serum GH, IGF-I, IGFPB-3 and leptin were evaluated in 38 corticosteroid-treated RA patients, 14 non-RA patients under corticosteroids (corticosteroid controls, CC) and 32 healthy controls (HC). Bone density was evaluated using dual X-ray absorptiometry (DEXA), and expressed as bone mineral density (BMD), and quantitative ultrasound (QUS). Body composition was assessed by DEXA. RESULTS: The three groups differed regarding femoral neck, total body BMD, lean mass and QUS parameters with lower values in the RA group (all P < or = 0.05). Growth hormone was higher in RA patients (P=0.0001) while IGF-I and IGFBP-3 did not differ between the three groups. In RA patients there was a tendency to high serum leptin levels and leptin strongly correlated with fat mass (r=0.83, P<0.0001), but not with bone mass measurements or inflammatory parameters. There were no differences for lean mass, GH and leptin between CC and HC. CONCLUSION: Our results suggest that these GH and leptin modifications could have an influence on both bone mass and body composition in RA.

High serum vascular endothelial growth factor correlates with disease activity of spondylarthropathies.

Angiogenesis is involved in chronic inflammatory joint diseases such as rheumatoid arthritis (RA). Vascular endothelial growth factor (VEGF) plays a crucial role in angiogenesis. The spondylarthropathies (SpA) are characterized by enthesitis and synovitis, in which blood vessels participate. The objective of this study was to investigate serum VEGF levels and their potential associations with disease activity markers for SpA. Sera were collected from 105 patients with SpA (72 with ankylosing spondylitis (AS), four with psoriatic arthritis (PsA), six with reactive arthritis (ReA), eight with enteropathic arthropathy and 15 with undifferentiated SpA), 50 patients with rheumatoid arthritis (RA) and 64 healthy controls. Disease activity in SpA patients was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and laboratory parameters of inflammation [erythrocyte sedimentation rate (ESR) and C-reactive protein level (CRP)]. Serum VEGF levels were significantly higher in SpA patients (316.4 +/- 215.6 pg/ml) and RA patients (405.2 +/- 366.5) than in controls (217.3 +/- 145.2) (P = 0.003). In SpA patients, serum VEGF levels correlated with disease activity indices (BASDAI: r = 0.22, P = 0.04; ESR: r = 0.3, P = 0.003; and CRP: r = 0.23, P = 0.02). Serum VEGF levels were not associated with presence of extra-articular manifestations or syndesmophytes or with the grade of sacroiliitis. These results suggest that VEGF and therefore angiogenesis may play a role in SpA pathogenesis and may serve as a disease activity marker in SpAs.

HLA-DRB1 alleles and shared amino acid sequences in disease susceptibility and severity in patients from eastern France with rheumatoid arthritis.

OBJECTIVE: To examine the effects of HLA-DRB1 alleles and amino acid sequences that carry the shared epitope (SE) upon rheumatoid arthritis (RA) susceptibility and disease severity in patients from Eastern France. METHODS: HLA-DRB1 alleles were determined in 120 patients and 104 healthy controls by polymerase chain reaction/sequence specific oligonucleotide probes. Subtyping of DRB1*01 and *04 were performed using sequence specific primers. Patients were retrospectively evaluated for disease duration, age at disease onset, presence of rheumatoid factors, subcutaneous nodules, vasculitis and other extraarticular diseases, for the need for arthroplasty and immunosuppressive/immunoregulatory agents, and for radiographic damage. RESULTS: The prevalence of HLA-DRB1*04 was significantly higher in patients (46.6%) than in controls (17.3%) (Pcorr = 0.000003). HLA-DRB1*0101 and *0401 were the most prominently associated subtypes in patients with RA (33.3%, Pcorr = 0.011, and 28.3%, Pcorr = 0.00008, respectively). A significant fraction of patients (72.5%) expressed one or 2 copies of the SE (p < 0.0000001; OR 4.77, CI 2.61-8.78). The presence of double SE was associated with a higher risk of developing RA (OR 4.83, CI 1.91-12.71; p = 0.0001). No significant differences in the clinical records among patients expressing no RA linked alleles, one and 2 copies of the SE, were observed. However, analyzing the specific effect of each amino acid sequence, we observed a significant association of the QKRAA motif with vasculitis (p = 0.03) and history of joint replacement surgery (p = 0.05), suggesting a role for lysine in position 71 of the shared sequence. CONCLUSION: These findings differ from those of previous HLA-DRB1 allele studies in patients with RA from other regions of France. Thus, the heterogeneity in both the expression of DRB1 alleles and the association of these alleles with disease severity could be relevant within a country such as France.

Relationship between urinary pyridinium cross-links, disease activity and disease subsets of ankylosing spondylitis.

OBJECTIVE: In this study, we aimed to determine the urinary levels of pyridinium cross-links and urinary beta-isomerized fragments derived from the C-telopeptide of the alpha1 chain of type I collagen (beta-CTX) as markers of bone resorption in patients with ankylosing spondylitis (AS), and to study their relationship to markers of disease activity [erythrocyte sedimentation rate (ESR)] and to disease subsets of this condition. METHODS: The serum calcium, osteocalcin (OC), parathormone (PTH), 25 OHD3 levels, beta-CTX and the urinary combined free pyridinolines (f-Pyr + f-Dpyr), urinary free deoxypyridinoline (f-Dpyr) and urinary free pyridinoline (f-Pyr) were evaluated and compared in 32 AS patients and 25 controls. Bone mineral density (BMD) was evaluated at the lumbar spine and the femoral neck. RESULTS: The serum markers of bone metabolism (serum calcium, PTH, 25 OHD3 and OC) were in the normal range in the AS group. AS patients had a lowered lumbar spine BMD (P = 0.01) (corresponding T score: P = 0.03), but femoral neck BMD did not differ significantly between AS and controls (P = 0.08) (corresponding T score: P = 0.11). There was no difference in the urinary levels of pyridinium cross-links and beta-CTX between AS patients and controls. A positive correlation between ESR, (f-Pyr + f-Dpyr) (r = 0.42; P = 0.018) and f-Dpyr (r = 0.49; P = 0.005) was observed. In the different disease subsets of AS, we found that patients with peripheral involvement had higher (f-Pyr + f-Dpyr) (P = 0.04) and f-Dpyr levels (P = 0.04), patients with early disease had elevated (f-Pyr + f-Dpyr) (P = 0.01), f-Dpyr (P = 0.02) and f-Pyr (P = 0.01) levels, and that those with raised ESR had enhanced f-Dpyr (P = 0.009) excretion. Patients were then stratified according to disease duration, peripheral involvement and sex, and this allowed us to observe that only urinary f-Dpyr remained elevated in patients independently from these variables and that raised ESR is the more relevant parameter for explaining this high level of excretion. CONCLUSION: We conclude that there was no difference in the levels of urinary pyridinium cross-links and beta-CTX between AS and controls. However, urinary excretion of some of these collagen compounds was enhanced in subgroups of AS, mainly in patients with raised ESR. Thus, AS patients with laboratory evidence of active disease could have a higher risk of bone loss.

Prospective study of the prevalence of bronchiectasis in rheumatoid arthritis using high-resolution computed tomography.

A prospective study of the prevalence of bronchiectasis in rheumatoid arthritis was conducted over an 18-month period in 46 patients (34 women and 12 men with a mean age of 60.1 years) meeting 1987 American College of Rheumatology criteria for rheumatoid arthritis. All patients underwent high-resolution computed tomography of the chest, whose results were confronted with a number of clinical, laboratory test and lung function testing parameters. Bronchiectasis or bronchiolectasis was found in 23 patients (50%) and was the most common abnormality detected by high-resolution computed tomography. When the four patients with isolated bronchiolectasis were excluded, the prevalence was 41%. Eighteen of the 23 patients had not been diagnosed with bronchiectasis before the study and 13 were free of respiratory symptoms. No significant differences were found between the 23 patients with and the 23 patients without bronchiectasis for age at onset or duration of the rheumatoid arthritis, extraarticular involvement, positive rheumatoid factors, bony erosions, use of corticosteroids or immunosuppressives, respiratory manifestations, smoking, or spirometry parameters. Patients without bronchiectasis were more likely to have impaired diffusion of carbon monoxide across the alveolar-capillary membrane. Among the patients with bronchiectasis, those with respiratory symptoms (n = 10) were more likely to have a history of lung disease and those without respiratory symptoms (n = 13) were more likely to have a diagnosis of bronchiectasis secondary to rheumatoid arthritis; no other differences were found between these two subgroups. Routine use of high-resolution computed tomography, a technique capable of demonstrating silent bronchiectasis, showed that bronchiectasis was the most common lung change in rheumatoid arthritis in our study. At the time of the study, there was no evidence that presence of bronchiectasis was associated with more severe joint or lung symptoms.

Relationship between urinary excretion of modified nucleosides and rheumatoid arthritis process.

The levels of the five methylated nucleosides pseudouridine (psi-Urd), 1-methyladenosine (1-MeAdo), 4 acetylcytidine (4-AcCyd), 1 methylinosine (1-Melno) and 7 methylguanosine (7-MeGuo) resulting from RNA degradation were examined in the urine of rheumatoid arthritis (RA) patients. Of these five, 1-MeAdo and psi-Urd were correlated with the active phase of the disease, while two others (4-AcCyd and 1-Melno), which require further evaluation, appeared to be linked to the prognosis of the disease. As RNA turnover is closely associated with cell proliferation, including that of lymphocytes in RA, there may be a hitherto unsuspected benefit in measuring 1-MeAdo and psi-Urd as biochemical markers of RA disease activity.

The B7 cross reactive group and spondyloarthropathies: an epidemiological approach.

OBJECTIVE: To study the association between the B7 cross reactive group (B7, B40) and spondyloarthropathy (SpA), taking into account patients with atypical features. METHODS: We studied the main clinical and paraclinical features of 51 patients with rheumatoid arthritis, 55 with SpA, 120 with mechanical diseases, and 160 with inflammatory rheumatism not fulfilling the diagnostic criteria currently used. This descriptive analysis was performed using multiple correspondence factorial analysis to identify subgroups among unclassified patients and select SpA variants. We compared HLA frequencies among these groups versus a control group. RESULTS: We identified a subgroup close to the axial SpA and related to B7 (OR:5.91, p = 0.0008), whereas B40 is related to patients close to the peripheral SpA. CONCLUSION: B7 is related to axial SpA variants manifested by inflammatory low back pain according to Calin's criteria, with either extraarticular signs or sacroiliitis. Followup of such patients is required to determine whether their disease is a new entity or can be considered SpA.