Increased serum and synovial fluid antibodies to immunoselected peptides in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the role of potential immunoselected phages displaying random peptides in addition to possible antigen leads in rheumatoid arthritis (RA) by assaying the levels of synovial fluid (SF) and serum antibodies to synthetic peptides. METHODS: Serum and SF antibodies from patients and controls were measured using an enzyme linked immunosorbent assay (ELISA). RESULTS: Sera and SF from RA patients reacted significantly more strongly to a 12 amino acid peptide, EFHELGDIAIAA, that shares a significant homology with collagen type IX, than did SF and sera from control groups (p < 0.0209 and p < 0.0115, respectively). In addition, the humoral responses to a 15 amino acid peptide, GGYGDGGAHGGGYGG, derived from the glycine-rich cell wall protein (GRP) 1.8, and to a 16 amino acid synthetic peptide, LGSISESRRALQDSQR, derived from the Proteus haemolysin protein were significantly stronger in RA patients compared with healthy individuals (p < 0.0001 and p < 0.0011, respectively). CONCLUSION: Our data indicate that peptide phage libraries can be used as tools for the identification of the (auto)antigen leads that may be responsible for the initiation, perpetuation, or both, of the immune response in patients with RA.     

Anti-tumor necrosis factor-alpha antibody treatment reduces serum CXCL16 levels in patients with rheumatoid arthritis

The aim of this study was to analyze the change of serum chemokins levels of CXCL16, CX3CL1/Fractalkine, and CXCL10/interferon-gamma inducible protein-10 (IP-10) with rheumatoid arthritis (RA), by infliximab treatment. The effects of infliximab treatment were studied in 23 patients with RA, over a period of 30 weeks. The serum levels of CXCL16, Fractalkine, and IP-10, were measured at the baseline, just before initial treatment, and at 14 and 30 weeks after the initial treatment, with infliximab by ELISA. The higher levels of serum CXCL16 in the RA patients before treatment with infliximab significantly decreased at 14 and 30 weeks after the initial treatment with infliximab, but the serum Fractalkine and IP-10 levels did not decrease significantly. Infliximab treatment significantly lowered the serum levels of CXCL16 in patients with RA. CXCL16 is one of the crucial chemokines regulated by infliximab treatment.     

Rheumatoid factor and serum IgG, IgM and IgA levels in rheumatoid arthritis with vasculitis.

The authors report a significant increase in the rheumatoid factor titre in rheumatoid arthritis patients with vasculitis. A significant rise in IgG and IgA levels was found in uncomplicated RA, when compared with a normal population. The IgM levels were not found to be elevated in this group of RA patients. In the RA patients with vasculitis, on the contrary, the three Ig classes are increased when compared with the normal population, and the IgM level is increased when compared with the uncomplicated RA group. Significant relation was found between log IgM and log R.F. titre in the RA group with vasculitis. It is shown that the mild reduction of serum (by dithiothreitol 0.004 M) causes a complete negativity of the R. F. in all cases. It is concluded that the haemagglutination and the latex precipitation in vitro are induced by IgM-R. F. and not by IgG and IgA-R. F. molecules. Only free sites of IgM-R.F. play a functional role in the determination of the R. F. -titre. The authors postulated that increase in IgM in RA patients with vasculitis is partially due to the presence of free IgM-R. F. molecules in serum. Finally it is concluded that hidden IgM-R. F. molecules in patients with lower R. F. titre are not quantified by immunodiffusion methods.     

Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti-cyclic citrullinated peptide antibody

OBJECTIVE: To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody levels among patients with rheumatoid arthritis (RA). METHODS: The study sample included 66 RA patients who completed double-blind, randomized clinical protocols and for whom baseline and followup serum samples were available. Anti-CCP and RF levels were measured using commercially available assay kits. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the association of response and disease duration with declines in antibody levels. RESULTS: Patients had a mean +/- SD age of 49.9 +/- 12.0 years and were predominantly female (n = 51; 77%). The mean +/- SD duration between the times at which the baseline and followup serum samples were obtained was 13.7 +/- 8.6 months. Among the 64 subjects with positive antibody at baseline, 33 (52%) experienced a > or =25% reduction in the anti-CCP antibody level during the course of treatment, and 35 patients (55%) had a > or =25% reduction in RF. After adjustment for the baseline anti-CCP antibody level, only a shorter disease duration (< or =12 months) was significantly associated with a decline in the level of anti-CCP antibody (OR 3.0, 95% CI 1.0-8.8), and no association with treatment response was observed. Conversely, treatment response was the only significant determinant of a decrease in RF levels (OR 3.6, 95% CI 1.2-10.4). CONCLUSION: Shorter disease duration predicts greater declines in anti-CCP antibody levels with treatment in RA. Although treatment response is a robust determinant of a decrease in RF, it does not appear to be associated with declines in the anti-CCP antibody level.     

Increased serum levels of interleukin-15 in rheumatoid arthritis with long- term disease

OBJECTIVE: To study the serum levels of IL-15 in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), seronegative spondyloarthropathies (SSd) and healthy donors. METHODS: The IL-15 serum levels were measured by ELISA in sera from 50 RA patients, 30 patients with SLE, 30 patients with SSd and 30 healthy donors. In RA patients, several clinical and demographic parameters were also obtained at the time of sample collection. IL-15 levels were compared in different RA subpopulations (positive or negative rheumatoid factor [RF], long term or recent onset disease, high or low disease activity). In addition, the possible association with other demographic and clinical parameters (gender, age, disease duration, etc) was also analysed. RESULTS: RA patients had significantly higher serum levels of IL-15 (102.4 +/- 150 pg/ml; p = 0.0001) than SLE patients (9.8 +/- 15.3 pg/ml), SSd patients (7.9 +/- 14.6 pg/ml) and healthy donors' (5.2 +/- 11.6 pg/ml). RA patients with a disease evolution less than 2 years showed lower IL-15 levels (33.7 +/- 62.2 pg/ml) than those with long-term disease (152.4 +/- 64.6 pg/ml; p = 0.004). In addition, a significant correlation between IL15 in serum and the number of disease-modifying antirheumatic drugs (DMARDs) prescribed was detected in RA patients (r = 0.42; p = 0.002). No association between IL-15 levels and age, gender, RF or disease activity was observed in this group. CONCLUSION: IL-15 is elevated in RA patients, specially in those with long term disease, compared to other rheumatic disorders. This finding supports that IL-15 is involved in the perpetuation of RA synovitis.     

Steady-state serum salicylate levels in hospitalized patients with rheumatoid arthritis

When the total daily drug dose was individualized to produce a steady-state serum salicylate concentration between 20 and 35 mg/dl, clinically acceptable fluctuations of serum concentrations occurred during both twice daily and three times daily administration. In 6 rheumatoid arthritis patients receiving choline magnesium trisalicylate, mean steady-state serum levels were the same, and the ranges of hourly mean concentrations during 8 and 12 hour dosage intervals were 19 to 27 mg/dl and 17 to 30 mg/dl, respectively. Changing the dosing interval from 8 to 12 hours required a 50% increase in the fractional doses, but resulted in an increase of only 3 mg/dl in mean peak concentration and a decrease of 1 mg/dl in mean minimum concentration.     

Rubella antibody levels in juvenile rheumatoid arthritis.

Increased rubella antibody titres have been reported in patients with juvenile rheumatoid arthritis (JRA) and it has been suggested that rubella virus may be of importance in the aetiology or pathogenesis of the disease. In the present study, rubella and rubeola antibody titres in 85 patients with JRA were compared to age- and sex-matched controls. 41% of the patients did not have rubella antibody, but the geometric mean titre of those with JRA who had antibody was slightly higher than that of the controls with antibody (58-9 against 42-7; P less than 0-05). The level of rubella antibody titre correlated with serum IgG levels. There was no difference in rubeola antibody titres between patients and controls, and rubeola antibody did not correlate with serum IgG. Fifteen JRA patients developed rubella antibody after rubella vaccine or natural disease. This did not result in unusually high antibody titres and was associated with a mild exacerbation of symptoms in only two patients. This study suggests that the slight increase in rubella antibody in JRA is a nonspecific manifestation of increased immunoglobulins.     

The serum levels of resistin in rheumatoid arthritis patients

OBJECTIVE: Adipocyte-derived resistin is a circulating protein implicated in insulin resistance, but the role of human resistin is uncertain because it is produced largely by macrophages. The aim of this study was to analyze serum resistin concentrations in rheumatoid arthritis (RA) patients to determine the role of resistin in human inflammatory diseases. MATERIALS AND METHODS: Resistin concentrations were assessed by ELISA in serum samples from 42 patients with RA. Serum samples from 38 healthy subjects acted as controls. We also evaluated the circulating levels of tumor necrosis factor- alpha (TNF-alpha) and disease activity markers in RA patients. RESULTS: In RA patients, serum resistin levels were significantly higher than those in healthy subjects. Serum resistin levels in RA patients were correlated with the RA disease activity markers, CRP and ESR. Furthermore, resistin levels in RA patients were significantly correlated with circulating levels of TNF-alpha. CONCLUSION: Serum resistin levels were significantly increased in RA patients and correlated with inflammatory markers and TNF-alpha, suggesting that resistin may play a role in the rheumatoid inflammatory process.     

Gold serum levels in children with juvenile rheumatoid arthritis.

Serum gold levels were monitored in 66 children with juvenile rheumatoid arthritis, treated with different i.m. dosage schedules of sodium aurothiomalate (Myocrisin, Pharma Rhodia). The ages of the children varied from 1 to 15 years. Gold serum levels in children were related to the dose of Myocrisin calculated per kg of body weight or per square metre of body surface area. The results of our study indicate that in order to achieve a peak serum level at about 500--600 microgram/100 ml (25--30 micromol/l) with weekly injections, the dose of Myocrisin should be about 0.7 mg/kg, or 20 mg/m2. In order to avoid excessively high gold serum concentrations, the maximum single dose should not exceed 27 mg/m2 of body surface area.     

Increased myeloperoxidase plasma levels in rheumatoid arthritis

High myeloperoxidase (MPO) serum levels have been shown in several inflammatory diseases, including rheumatoid arthritis (RA). However, the correlation between MPO levels and disease activity in RA patients is still controversial. The aim of the study was to determine MPO plasma levels in RA patients and to investigate potential correlations between MPO levels and disease activity and treatment. MPO plasma levels were measured by ELISA according the manufacturer’s instructions. Disease activity was measured by DAS28 ESR and DAS28 CRP scores, and patients were classified into 4 groups: group 1 DAS28?<?2.6; group 2: 2.6?≤?DAS28?≤?3.2; group 3: 3.2?<?DAS28?≤?5.1 and group 4: DAS28?>?5.1. Rheumatoid factor (RF) was measured by latex agglutination test, and anti-cyclic citrullinated peptide (anti-CCP) antibodies were detected by ELISA with a commercial kit. Fifty-seven female RA patients (mean age: 46.02?±?13.47?years, mean disease duration: 115.77?±?99.44?months) and sixty gender- and age-paired healthy controls were included. Mean MPO plasma levels were significantly higher in patients than in controls (72.27?pM vs. 40.78?pM, P?=?0.007). RF was found in 59.6% and anti-CCP in 80.7% of the RA patients. No significant difference in MPO levels was seen among the four RA disease activity groups. We did not find significant correlation between MPO levels and disease activity as measured by DAS28 score. In conclusion, we observed significantly higher MPO plasma levels in RA patients when compared to healthy controls. However, we did not find correlation between MPO plasma level and disease activity.     

Effect of staphylococcal enterotoxin B on specific antibody production in children with atopic dermatitis.

Exotoxins secreted by Staphylococcus aureus have been identified as a possible trigger factor in atopic dermatitis (AD). We investigated the production and role of circulating antibodies, with specificity to staphylococcal enterotoxin B (SEB), in children with AD compared with those of healthy controls. The children with AD had significantly higher levels of serum SEB-specific immunoglobulin G (IgG; p = 0.0193), IgM (p = 0.011), and IgE (p = 0.0001) than the nonatopic children. The proportions of IgG, IgM, and IgE seropositivity in children with AD were 52.5% (21/40), 62.5% (25/40), and 67.5% (27/40), respectively. The levels of SEB-specific IgE and the severity of AD (p = 0.0004) were compared, but no correlation was seen for IgG or IgM. SEB may be involved in exacerbation of AD. SEB-specific IgE may be an important index of the clinical severity of AD. The SEB-specific IgG or IgM was produced during the exposure to the SEB antigen but may not be protective against SEB in AD.     

类风湿关节炎中抗纤聚蛋白抗体意义的探讨

目的探讨抗纤聚蛋白抗体(AFA)在类风湿关节炎(RA)中的意义,并比较AFA与类风湿因子(RF)、抗角蛋白抗体(AKA)、抗核周因子(APF)和抗环瓜氨酸肽(CCP)抗体以及某些临床指标的相关性。方法对860例研究对象,包括388例RA患者(其中早期172例,中晚期216例),422例非RA的风湿性疾病患者,50名健康对照,用免疫印迹法(IB)检测血清中的AFA。同时检测其他RA相关自身抗体。结果AFA在早期RA病例中阳性率为62.2%,在中晚期RA病例中阳性率为58.8%,对RA诊断敏感性60.3%,特异性91.1%,阳性和阴性预测值分别为94.6%、68.0%。AFA和AKA在早期和中晚期RA的阳性率差异无统计学意义,而RF、APF和抗CCP抗体在中晚期组的阳性率大于早期组。AFA与RF、AKA、APF以及抗CCP抗体相关(P<0.05)。AFA与RA患者平均发病年龄相关(P=0.047)。结论AFA可视为RA的特异性血清学标记,尤其对RF阴性及早期RA诊断很有帮助;AFA与其他RA相关自身抗体相关,联合检测可以相互补充,提高对RA的诊断。     

Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti–cyclic citrullinated peptide antibody

Objective

To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti‐CCP) antibody levels among patients with rheumatoid arthritis (RA).

Methods

The study sample included 66 RA patients who completed double‐blind, randomized clinical protocols and for whom baseline and followup serum samples were available. Anti‐CCP and RF levels were measured using commercially available assay kits. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the association of response and disease duration with declines in antibody levels.

Results

Patients had a mean ± SD age of 49.9 ± 12.0 years and were predominantly female (n = 51; 77%). The mean ± SD duration between the times at which the baseline and followup serum samples were obtained was 13.7 ± 8.6 months. Among the 64 subjects with positive antibody at baseline, 33 (52%) experienced a ≥25% reduction in the anti‐CCP antibody level during the course of treatment, and 35 patients (55%) had a ≥25% reduction in RF. After adjustment for the baseline anti‐CCP antibody level, only a shorter disease duration (≤12 months) was significantly associated with a decline in the level of anti‐CCP antibody (OR 3.0, 95% CI 1.0–8.8), and no association with treatment response was observed. Conversely, treatment response was the only significant determinant of a decrease in RF levels (OR 3.6, 95% CI 1.2–10.4).

Conclusion

Shorter disease duration predicts greater declines in anti‐CCP antibody levels with treatment in RA. Although treatment response is a robust determinant of a decrease in RF, it does not appear to be associated with declines in the anti‐CCP antibody level.

     

Relationship of serum IgG rheumatoid factor to IgM rheumatoid factor and disease activity in rheumatoid arthritis

Rheumatoid factors (RF) constitute the major autoantibodies in rheumatoid arthritis (RA). RF are directed against IgG Fc, are polyclonal, and are predominantly of the IgG and IgM classes. RF may participate in both synovial and extraarticular inflammation in RA, although the precise roles of serum IgG and IgM RF are unclear. The purpose of our study was to correlate serum IgG RF with serum IgM RF levels measured by radioimmunoassay and with clinical disease activity in 42 prospectively evaluated seropositive RA patients. IgM RF correlated with IgG RF levels and articular disease activity. IgG RF correlated with IgM RF but not with articular disease activity when adjusted for IgM RF.     

Leptin serum levels are not correlated with disease activity in patients with rheumatoid arthritis.

Leptin, the ob gene product, has been proposed as a mediator of inflammatory cytokine-dependent decreased food intake and cachexia in rodents. In humans, leptin serum levels increase after administration of tumor necrosis factor-alpha (TNF-alpha) or interleukin-2 or during septicemia. However, the effect of human chronic inflammatory disease on serum leptin is unknown. We therefore determined the serum leptin level (radioimmunoassay), body mass index (BMI), percent body fat ([%BF] bioelectrical impedance analysis), and disease activity (Disease Activity Score [DAS]) in 58 patients with rheumatoid arthritis (RA) and 16 controls. The BMI, %BF, serum leptin, and ratio of leptin to %BF (leptin/%BF) did not differ significantly in 25 patients with moderate RA activity (DAS, 3.6 +/- 0.5), 33 patients with low RA activity (DAS, 1.8 +/- 0.5), and controls. A positive correlation for serum leptin and %BF was detected in all groups. Our data indicate that in RA, a human chronic cytokine-mediated inflammatory disease, the serum leptin level is directly related to %BF but not to disease activity.     

Increased levels of antibodies to cytokeratin 18 in patients with rheumatoid arthritis and ischaemic heart disease

OBJECTIVE: To determine whether raised levels of antibodies to CK18 in patients with RA are associated with ischaemic heart disease (IHD). METHODS: IgA, IgG, and IgM antibodies to CK18 were measured by enzyme linked immunosorbent assay (ELISA) in patients with RA with (n = 34) or without (n = 28) IHD. The relationship between CK18 antibody levels and markers of inflammatory and/or cardiovascular disease was examined. RESULTS: Initial analysis showed that IgG antibody levels to CK18 were higher in patients with RA with IHD than in those without (50.1 v 34.5 AU, p = 0.047), although significance was lost after correction for multiple comparisons. Further analysis showed a significant difference (p = 0.015) between patients with IHD and a positive family history, and patients without IHD and a negative family history (53.7 v 29.0 AU, Kruskal-Wallis multiple comparison Z value test). There was also a significant trend of increasing 10 year cardiovascular risk with increasing CK18 IgG antibody levels (p = 0.01). No association was found between CK18 antibody levels and conventional markers of inflammation or cardiovascular disease, but an association was found between levels of CK18 IgG and IgG antibodies to cytomegalovirus (CMV) (Spearman's r(s) = 0.379, p(corr) = 0.04). No evidence for cross reactivity of CK18 antibodies with CMV antigens was found. CONCLUSION: Levels of IgG antibodies to CK18 are raised in patients with RA with IHD, particularly if they also have a positive family history. This may reflect damage to CK18 containing cells in the cardiac vasculature and/or in atherosclerotic plaques, and may be a useful additional marker for the identification of patients with, or likely to develop, IHD.