The autonomic nervous system and the immune system in juvenile rheumatoid arthritis

CD16, the low affinity receptor for monomeric IgG (Fc gamma RIIIA), is a well characterized activation molecule on NK cells. In this study we investigated the role of CD16 in NK cell-mediated regulation of immunoglobulin production. Cocultures of the CD16+ human NK clone CNK6 and highly purified SAC/IL-2-activated B lymphocytes with various CD16 antibodies showed significantly diminished NK-enhanced immunoglobulin production in a dose-dependent manner, indicating that CD16 is relevant in NK-B cell interaction. Similarly, recombinant soluble CD16 incubated with B cells before cultures, suppressed the NK cell-stimulated B cell antibody response. Enhanced immunoglobulin production was also inhibited by Fc-specific F(ab')2 anti-body fragments. Coculture of NK cells with B lymphocytes resulted in induction of mRNA for IFN-gamma and TNF-alpha. The accumulation of mRNA for these cytokines was prevented by addition of CD16 and Fc-specific antibodies. It is proposed that interaction of CD16 on NK cells with B cell bound immunoglobulin leads to induction of cytokines in NK cells which stimulate immunoglobulin production by B cells.     

Anti-Sa antibody is an accurate diagnostic and prognostic marker in adult rheumatoid arthritis

The aporphine alkaloids boldine and glaucine have been reported to show "neuroleptic-like" actions in mice, suggesting that they may act as dopamine antagonists. We have found that in vitro boldine displaces specific striatal [3H]-SCH 23390 binding with IC50 = 0.4 microM and [3H]-raclopride binding with IC50 = 0.5 microM, while the affinities of glaucine at the same sites are an order of magnitude lower. In vivo, however, 40 mg/kg boldine (i.p.) did not modify specific striatal [3H]-raclopride binding and only decreased [3H]-SCH 23390 binding by 25%. On the other hand, 40 mg/kg glaucine (i.p.) displaced both radioligands by about 50%. Behaviors (climbing, sniffing, grooming) elicited in mice by apomorphine (0.75 mg/kg s.c.) were not modified by boldine at doses up to 40 mg/kg (i.p.) but were almost completely abolished by 40 mg/kg glaucine (i.p.). In the apomorphine-induced (0.1 mg/kg s.c.) rat yawning and penile erection model, boldine and glaucine appeared to be similarly effective, inhibiting both behaviors by more than 50% at 40 mg/kg (i.p.). Boldine and glaucine, injected i.p. at doses up to 40 mg/kg, were poor modifiers of dopamine metabolism in mouse and rat striatum. These data suggest that boldine does not display effective central dopaminergic antagonist activities in vivo in spite of its good binding affinity at D1- and D2-like receptors, and that glaucine, although less effective in vitro, does appear to exhibit some antidopaminergic properties in vivo.     

Evaluation of interleukin-6 in rheumatoid arthritis as an activity criterion

This study evaluated interleukin-6 levels as an activity criterion in rheumatoid arthritis (RA) and compared if with other activity criteria. We evaluated 35 patients with active RA, 31 with inactive RA, and 25 patients with osteoarthritis, in addition to 28 healthy individuals. Serum interleukin-6 levels were higher in active RA patients than in those with inactive RA, or osteoarthritis and healthy individuals (P < 0.001). Serum interleukin-6 levels of patients with active RA were positively correlated with the erythrocyte sedimentation rate, C-reactive protein, and alpha 2-globulin levels (P < 0.001), but there was a negative correlation with serum albumin levels (P < 0.05). We conclude that interleukin-6 can be responsible for both the most systemic manifestations of RA and for its local manifestations.     

Detection and characterization of circulating immune complexes in rheumatoid arthritis

Circulating immune complexes (IC) were detected and quantified in serum of patients with rheumatoid arthritis (RA) by three methods: radiolabeled Clq binding test, anticomplementary activity and optical density of 3% PEG precipitated sera. Rheumatoid factor (RF) is characterized in PEG precipitates by the Waaler-Rose reaction. The relationship between IC, complement and RF levels are analyzed.     

Naturalistically observed sighing and depression in rheumatoid arthritis patients: A preliminary study.

Objective: This study tested the degree to which naturalistically observed sighing in daily life is a behavioral indicator of depression and reported physical symptoms (i.e., experienced pain and flare days) in rheumatoid arthritis (RA) patients. Design: Thirteen RA patients wore the Electronically Activated Recorder (EAR), an observational ambulatory assessment tool, for two weekends (Friday through Sunday) approximately one month apart. The EAR periodically recorded snippets of ambient sounds from participants' momentary environments (50 s every 18 min). Sighs were coded from the sampled ambient sounds. Main Outcome Measures: Depression was assessed with the Center for Epidemiological Studies Depression Scale and the Beck Depression Inventory. Pain during the past month was assessed with a 10-cm visual-analog scale, and number of flare days during the prior 6 months was reported. Results: Sighing was significantly and strongly related to patients' levels of depression and nonsignificantly and less strongly related to their reported pain and number of flare days. Conclusion: The findings suggest that sighing can serve as an observable marker of depression in RA patients. Because the sample size was small, the findings should be considered preliminary. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Activation of the haemostatic system in children with juvenile rheumatoid arthritis correlates with disease activity

Twenty-four children with juvenile rheumatoid arthritis (JRA) and 10 children with postinfectious arthropathies were investigated for markers of blood coagulation and fibrinolytic activity: Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and D-Dimer were measured using solid phase enzyme linked immunosorbent assays (ELISA). Results were compared with clinical and conventional laboratory signs of disease activity. F1+2, TAT, D-Dimer, and fibrinogen were significantly elevated in children with JRA as compared with healthy children and children with postinfectious arthropathies. F1+2, TAT, and D-Dimer correlated significantly with disease activity, assessed by determination of the joint index score and C-reactive protein (CRP). The study demonstrates a subclinical activation of the haemostatic system in children with JRA correlating with disease activity, which might be caused by the action of several immunomediators on cells (monocytes, endothelial cells) playing a role in the regulation of blood coagulation activity.     

Assessment of disease activity in rheumatoid arthritis using magnetic resonance imaging: quantification of pannus volume in the hands

We attempted to assess whether pannus volume measured by magnetic resonance imaging (MRI) can be used as an indicator of disease activity in rheumatoid arthritis (RA). Eleven women (mean age 46 yr) with uncontrolled RA were studied for 1 yr. Pannus formation in both hands was quantified using MRI at the start of the study, and at 6 and 12 months thereafter. The volume of enhancing pannus (VEP) was compared with changes in the radiological scores, grip strength, joint tenderness counts, joint swelling counts, erythrocyte sedimentation rate (ESR), and serum C-reactive protein (CRP). Patients were classified into three groups based on VEP changes between 0 and 12 months: unchanged (n = 2), decreased (n = 6) and increased (n = 3). VEP at 6 months and at 12 months differed significantly between the three groups. No statistically significant differences were found between the groups in radiographic scores, physical parameters or laboratory parameters despite the fact that some of these parameters changed in the direction indicated by the changes in VEP. VEP can be used as a new indicator to assess disease activity in individual RA patients and, using this parameter, treatment outcome can be assessed in fewer subjects than with traditional measures.     

Urinary neopterin excretion and dihydropteridine reductase activity in rheumatoid arthritis

A 61-day short-term prospective study comparing the efficacy of Chemiron capsules (Ferrous Fumarate 300 mg, Folic Acid 5 mg, Vitamin B12 10 ug, Vitamin C 25 mg, Magnesium sulphate, 0.3 mg and Zinc Sulphate 0.3 mg) with conventional ferrous gluconate and folic acid administration has shown that both haematinic regimens improve haematological indices in normal pregnant women. A significant rise in haemoglobin was seen in the Chemiron group on days 5 and 19 whereas a significant increase in packed cell volume was observed on days 5, 19 and 61. There were no significant differences between the mean value of platelets during the therapy period in either group. A significant rise in the mean reticulocyte values could be demonstrated in the Chemiron group throughout the study period. This study further shows that Chemiron has a better haematological effect than Ferrous Gluconate at the dosage used.     

Changes in the respiratory system of patients with rheumatoid arthritis--personal observations

13 patients with RA admitted to our Institute with symptoms of respiratory involvement were described. Taking under consideration pulmonary function tests, radiological findings and histological examinations, we recognised 7 cases with interstitial lung disease, 3 cases with recurrent respiratory infection with bronchiectasis, 1 case with pleuritis, 1 with Caplan's syndrome and 1 with alveolar haemorrhage. The role of RF, and treatment with gold in the development of interstitial lung disease, as well as character of physiologic abnormalities concerning the small airways and its potential connection with bronchiolitis were discussed.     

Nutrition and the immune system: an introduction

Nutrition is a critical determinant of immune responses and malnutrition the most common cause of immunodeficiency worldwide. Protein-energy malnutrition is associated with a significant impairment of cell-mediated immunity, phagocyte function, complement system, secretory immunoglobulin A antibody concentrations, and cytokine production. Deficiency of single nutrients also results in altered immune responses: this is observed even when the deficiency state is relatively mild. Of the micronutrients, zinc; selenium; iron; copper; vitamins A, C, E, and B-6; and folic acid have important influences on immune responses. Overnutrition and obesity also reduce immunity. Low-birth-weight infants have a prolonged impairment of cell-mediated immunity that can be partly restored by providing extra amounts of dietary zinc. In the elderly, impaired immunity can be enhanced by modest amounts of a combination of micronutrients. These findings have considerable practical and public health significance.     

Perinuclear antineutrophil cytoplasmic antibody in rheumatoid arthritis: a marker of severe disease with associated nephropathy

OBJECTIVE: To evaluate the clinical significance of antineutrophil cytoplasmic antibodies (ANCA) in patients with rheumatoid arthritis (RA), and especially in those with clinically suspected or histologically proven nephropathy. METHODS: A total of 246 RA patients with (n = 149) and without (n = 97) histologically proven (n = 99) or clinically suspected (n = 50) nephropathy were studied for the presence of ANCA by immunofluorescence and enzyme immunoassay. RESULTS: Perinuclear ANCA (pANCA) were found in 52 (21%) of the 246 patients. Patients with clinically suspected or histologically proven nephropathy were significantly more frequently positive for pANCA (30% versus 7%; P < 0.00005) and had significantly higher mean (+/- SD) pANCA log titers (103 +/- 5.6 versus 27 +/- 3.0; P = 0.0011) than patients without clinically evident renal disease. Positivity for pANCA was associated with clinical and laboratory findings indicating severe basic disease and increased inflammatory activity. Irrespective of this association, pANCA acted as a significant and independent predictor of RA-associated nephropathy. CONCLUSION: Perinuclear ANCA in RA indicate severe disease with increased inflammatory activity. There is an especially strong and independent association between pANCA and RA-associated nephropathy.     

A probable explanation for mild extra-articular manifestations in Indian patients of rheumatoid arthritis: a preliminary study

The combination of a total lower lip, chin, and anterior mandibular defect following cancer resection is an extremely complex problem that requires a sequence of operations to optimize functional and aesthetic results. One patient is presented in whom the defect was reconstructed with a free fibular flap followed by a series of ancillary procedures using both modern and traditional techniques. At the time of tumor ablation, the through-and-through oromandibular defect was reconstructed with a fibular osteocutaneous flap. The lower lip and gingivolabial sulcus was reconstructed later with a tongue flap. Tissue expansion was subsequently used to replace the fibular skin with expanded submental hair-bearing skin. A polyethylene implant was added later to the fibular bone for chin augmentation. Subsequently the lower lip was supported with a tendinous graft suspended to the anterior masseter bilaterally. Lastly, the vermilion border was elevated by removing a rim of the tongue flap and covering the secondary wound with a full-thickness skin graft. At the end of the reconstructive procedures, lip seal and oral aperture were good with no drooling and excellent speech.     

Elderly rheumatoid arthritis patients on steroid treatment tolerate physical training without an increase in disease activity

The effects of physical training on elderly, fragile patients with rheumatoid arthritis (RA) who are on low-dose steroids were investigated. The controlled study included 24 patients who had been treated with low-dose steroids for 2 years. Each patient was assigned either to a treatment group receiving training or to an untrained control group. The training took place over a 3-month period and was based on a protocol using progressive interval training consisting of bicycle exercises, heel lifts, and step-climbing. The exercises were performed twice weekly for 45 minutes. Comparison of the two groups showed that disease activity did not increase in the trained group and that fewer, but not significantly fewer, swollen joints were observed in this group (p = 0.06). No significant changes were noticed in erythrocyte sedimentation rate, tender joints, or morning stiffness. The work capacity of the trained patients were doubled and the numbers of repetitions increased 76%. Individually adapted exercise programs can therefore be recommended for elderly rheumatoid arthritis patients on steroid treatment.     

Relation between exploratory activity and immune function in aged mice: a preliminary study

Previous studies show that fast exploration of a T-shaped maze by mature mice may predict an above average longevity. Since the nervous and the immune systems work in a coordinated fashion, and it seems that these two homeostatic systems both influence organismic aging and suffer a senescent decline, we have performed a comparative study of the above behavioral parameter and different functions of three representative immune cells: lymphocytes, macrophages and natural killer (NK) cells obtained from old (76 +/- 1 weeks of age) female OF1-Swiss mice. At 70 weeks of age the mice were divided into a 'fast' and a 'slow' group, containing 100 and 0%, respectively, of animals able to explore the 50 cm-long first arm of the maze in 20 s or less. At 76 +/- 1 weeks of age the animals were sacrificed, the peritoneal cell suspensions were obtained and the immune organs (axillary nodes, spleen and thymus) were isolated. The following leukocyte functions were studied in peritoneal macrophages: adherence to substrate, mobility (spontaneous and chemotaxis), ingestion of particles and superoxide anion production whereas mobility, lymphoproliferative response to the mitogen Con A and NK activity were studied in the immune-organ leukocyte suspensions. The results show that the aged fast mice have better immune functions than the aged slow mice.     

Tissue-specific galactosyltransferase abnormalities in an experimental model of rheumatoid arthritis

The aim of our study was to determine whether the minor polar components of virgin olive oil could have favorable effects (1) on fasting and postprandial lipid profile and (2) on low-density lipoprotein (LDL) composition and susceptibility to oxidation in vitro. Ten normolipidic subjects were included in a crossover study (two diet periods of 3 weeks) and received either virgin olive oil (OO diet) or oleic acid rich sunflower oil. An oral fat load was performed at the end of each period. The plasma lipid levels were not significantly different after both diets in the fasting and postprandial states. A few minor variations of the LDL composition were observed only in the postprandial lipemia, and they were different after both diets. The LDL oxidation susceptibility was evaluated by the formation of conjugated dienes. With LDL isolated in the fasting state, the diene production decreased (p = 0.0573) only after the OO diet. The dienes determined at time 0 and the maximal dienes obtained during the oxidation reaction decreased (p = 0.0145 and p = 0.0184, respectively) only after the OO fat load. Nevertheless, the diene production decrease was not significant (p = 0.0848). Our results suggest a mild effect of minor components of virgin olive oil related to a decrease of LDL susceptibility to oxidation; further analyses are necessary to give clear conclusions about their role.