IgG3 reactive rheumatoid factor in rheumatoid arthritis: etiologic and pathogenic considerations

Rheumatoid factor (RF) is a polyclonal autoantibody directed against the Fc portion of IgG. Although the role of RF in patients with rheumatoid arthritis (RA) is unclear, immune complexes that form between RF and IgG can activate the classical complement (C) pathway, leading to pathogenic outcomes involving inflammatory events and tissue damage. The specificity of serum RF and RF produced by rheumatoid synovial cells (RSC) is different. Serum RF has specificity for rabbit IgG and human IgG subclasses IgG1, 2, and 4, but binds poorly to IgG3. The affinity of serum RF for IgG Fc is low, having an association constant of 10(4)-10(5) M-1. RSC RF, however, has specificity for human IgG and high avidity for IgG3. Because of this greater specificity and avidity for IgG3, and because RSC RF may be pathogenically more important than serum RF, an important role for IgG3-reactive RF in RA may exist. Binding of RF to IgG may be dependent on the allotype and glycosylation of IgG. Infectious agents present in RA patients may directly or indirectly induce the production of certain RF. In this communication, we review and expand on several observations examining the role of IgG3-reactive RF in RA including: 1) binding differences between RF derived from RSC and serum; 2) glycosylation characteristics of IgG and its interaction with RF; 3) apparent allotype dependent binding of IgG3-reactive RF; and 4) possible relationship between infectious agents and the production of IgG3-reactive RF. Taken together, these observations suggest an important role for IgG3-reactive RF in better understanding the etiology and pathogenesis of RA.     

Importance of reactive oxygen species in rheumatoid arthritis

Free radical oxidation--peroxidation products, superoxide dismutase (SOD) activity--and nonproteic thiols were measured in blood from 10 normal subjects and 10 patients with rheumatoid arthritis (RA). Peroxidation products and SOD activity have been found significantly elevated, while blood nonproteic thiols have been found significantly lower in RA patients, as compared to normal controls. Also, plasmatic concentration of ceruloplasmin has been found significantly higher in RA patients than in controls.     

The significance of fibronectin in cryoprecipitation in rheumatoid arthritis and other diseases

Fibronectin, a glycoprotein produced by mesenchymal cells, was present in 11 of 16 plasma cryoprecipitates and 12 of 14 synovial fluid (SF) cryoprecipitates. In some SF cryoprecipitates it was the major protein component. Fibronectin levels were related to the development of serum turbidity in the cold and fibronectin was involved in the development of cold turbidity induced by some charged polysaccharides in plasma, serum, and SF. It is suggested that fibronectin, which is synthesized by vascular endothelial cells and synovial lining cells, is involved in the development of some cryoprecipitates in patients with rheumatoid arthritis and other diseases.     

The level of serum thymic activity in patients with rheumatoid arthritis and systemic lupus erythematosus

Thymic serum activity (TSA) has been studied in 52 healthy subjects, 48 rheumatoid arthritis patients and 17 sufferers with systemic lupus erythematosus aged from 18 to 70. TSA was compared in patients under and over 40 years. In those under 40 TSA appeared significantly inhibited, while in older subjects it did not differ from age-matched control. No correlations were reported between TSA levels and clinical characteristics. Changes in TSA levels may be related both to low content of thymic hormones and formation of inactive complexes from thymic mediators with inhibitors.     

High serum prolactin levels in men with rheumatoid arthritis

OBJECTIVE: High prolactin (PRL) levels have been reported in systemic lupus erythematosus, Reiter's syndrome, and psoriatic arthritis. However, results of PRL investigations in rheumatoid arthritis (RA) are contradictory. We evaluated the PRL status in men with RA and the possible effect on bone mineral density (BMD). METHODS: We studied 91 men with RA and 68 controls. PRL serum levels were analyzed under standardized conditions. Sex hormones (testosterone, androstenedione, and DHEAS) were also studied. BMD was analyzed at L2-L4 and the femoral neck by Hologic QDR1000. Comparative tests, linear correlations, and multiple regression analysis were performed. RESULTS: Serum PRL levels were significantly higher in men with RA (249+/-162 mU/l) than in controls (189+/-85 mU/l) (p=0.0015). High PRL levels were significantly correlated with the duration of RA (r=0.23; p=0.01) and with functional stage according to the Steinbrocker classification (r=0.24; p=0.01). High PRL concentrations were not correlated with the low levels of androgens observed in males with RA. Femoral BMD showed a negative correlation with PRL concentrations (r=0.20; p=0.04). Nevertheless, PRL was not a significant determinant of BMD. CONCLUSION: Men with RA have high serum PRL levels and concentrations increase with longer disease evolution and worse functional stage. Prolactin levels do not have a direct effect on BMD.     

Immunoglobulin E-rheumatoid factor in the serum of patients with rheumatoid arthritis, asthma, and other diseases

A solid-phase radioimmunoassay was developed to detect immunoglobulin (Ig)E antibodies that bound to human IgG. IgE-rheumatoid factor activity was found in the serum of 18 of 20 patients with seropositive rheumatoid arthritis, 1 of 4 patients with seronegative rheumatoid arthritis, 3 of 32 patients with seronegative rheumatoid arthritis, 3 of 32 patients with asthma, and in 1 patient with hypocomplementemic vasculitis and iodide sensitivity. Immunopathologic implications of IgE-rheumatoid factor are discussed.     

Hemoglobin levels correlate with serum soluble CD23 and TNF-Rs concentrations in patients with rheumatoid arthritis

BACKGROUND: Global and regional changes in cerebral energy utilization are reported to characterize late life depression. METHODS: Twenty seven subjects with late life depression (9 prior to starting medication, 18 after starting) and 27 matched controls were evaluated with cordance, a quantitative EEG measure that reflects cerebral energy utilization. RESULTS: Global and focal (anterior and centrotemporal) differences were present in theta-band cordance between unmedicated depressed and control subjects. Depressed subjects receiving treatment had cordance patterns similar to controls. CONCLUSIONS: The presence of both diffuse and focal disturbances in energy utilization prior to initiating treatment indicates that cordance detects altered cerebral physiology in depressed patients, and that this measure may also be sensitive to treatment interventions.     

Chloroquine retinopathy in patients with rheumatoid arthritis

The paper presents data on the differential fertility of schizophrenics and controls, and the fertility of their siblings. This study used several methodological procedures in the study of schizophrenia reproduction, which strengthens the validity of the findings. Firstly, both male and female rates were examined. Secondly, the method of selection of a control avoided the biases introduced by using census data or other non-matched controls. Third, a diagnostic criterion was used which minimizes the possibility of the inclusion of other psychiatric illnesses. The results obtained support prior reports of the lowered reproductive rates of schizophrenics. Further, the siblings of schizophrenics were found not to have a reproductive advantage when contrasted to control siblings. The failure to find a reproductive advantage conflicts with a hypothesis of a balanced polymorphism as the mechanism maintaining an apparent constant rate of schizophrenia.     

HLA-DM polymorphisms in patients with rheumatoid arthritis

OBJECTIVE: To investigate the contribution of HLA-DMA and DMB genes, which play a crucial role in the HLA class II restricted antigen presentation pathway, in susceptibility to rheumatoid arthritis (RA). METHODS: The distribution of DMA and DMB alleles was examined in patients with RA and in healthy subjects by oligotyping of PCR amplified genomic DNA with sequence specific oligonucleotide probes. RESULTS: There were no significant differences in the prevalence of DMA and DMB alleles in patients with RA as compared to healthy controls. In addition, no significant differences in frequencies of DMA and DMB alleles were observed in RA susceptibility epitope positive RA patients and controls. CONCLUSION: DMA and DMB genes do not appear to play a role in susceptibility to RA.     

Ankle arthrodesis in patients with rheumatoid arthritis

The results of 26 ankle arthrodeses performed for rheumatoid arthritis on 21 patients were reviewed. Tibiotalar arthrodesis was performed in 14 ankles, and tibiotalocalcaneal arthrodesis was performed in 12. External fixation was used in 20 ankles, and internal fixation was used in six. Followup was available in 24 of 26 ankles (19 patients), and averaged 5 years (range, 2-8 years). There was no pain experienced in 19 ankles; mild, occasional pain was experienced in four ankles; and moderate, daily pain was experienced in one ankle. Daily activities were limited in five patients and recreational activities were limited in 11. All patients reported some difficulty walking on uneven terrain. Nearly all patients were satisfied; two were satisfied with reservations and two were dissatisfied. Union was achieved in 25 of 26 (96%) ankles. Ankle arthrodesis is an effective operation in patients with rheumatoid arthritis. Unlike previous reports, union and complication rates in this series were comparable with rates for arthrodesis for posttraumatic and degenerative arthritis.     

Lymphocyte depletion in patients with rheumatoid arthritis

Sixteen patients with severe rheumatoid arthritis, marked inflammation of the synonvial membrane and high rheumatoid titer were cannulated by the thoracic duct for a period rangin between 82 up to 100 days. The patients being not under any medication during that time. Quantitative and qualitative analysis of the lymphocytes were performed, as well as responses to mitogens, rheumatoid factor, circulating antibodies and delayed hypersensitivity. By the 14th day nearly all the patients had a partial or almost complete remission of their disease. No complications were observed. These results will be discussed.     

Immunological findings in serum and synovial fluid in patients with rheumatoid arthritis (author's transl)

Sera and synovial fluid were investigated in 45 patients with rheumatoid Arthritis and 50 patients with osteoarthritis in inflammatory exacerbation (control group). The following tests were performed: IgG, IgM, IgA determinations, complement components C3, C3, C4, C3-proactivator, ceruloplasmin, electrophoresis, LDH and total acid phosphatase. 1. Serum levels of the ceruloplasmin, alpha 1, alpha 2 and gamma fractions of electrophoresis are significantly higher in patients with rheumatoid arthritis than in patients with osteoarthritis. 2. Synovial fluid: a) There is a significantly higher concentration of IgG, IgM, IgA, C3-proactivator and total acid phosphatase in the synovial fluid of patients with rheumatoid arthritis. b) C4 is significantly lower in patients with rheumatoid arthritis. c) Both groups were also compared with the help of a point system. Every patient received a plus point when the following criteria were seen: IgM greater than 150 mg/100 ml, C3 greater than 50 mg/100 ml, ceruloplasmin greater than 35 mg/100 ml, alpha 1 greater than 0.21 g%, alpha 2 greater than 0.44 g%, beta greater than 0.60 g% and gamma fraction on electrophoresis greater than 0.90 g%. Another point was added if the criteria ceruloplasmin greater than 22 mg/100 ml and C4 less than 17 mg/100 ml were simultaneously seen. With the help of this points system 48 out of the 50 osteoarthritis patients (96%) received zero points, one received 1 point and one 2 points, as opposed to the patients with rheumatoid arthritis where 35 out of 45 (78%) received one or more points. d) The differentation is not improved through additional testing of the rheumatic factors.     

Prevalence and depression degree in patients with rheumatoid arthritis

BACKGROUND: Study goals were: a) to know the existence and depressive level among a series of rheumatoid arthritis (RA) patients; b) to assess differences in depression levels of individuals with and without RA, and c) to identify the association of depression level with socioepidemiological, clinical, and prognostic characteristics in these patients. MATERIAL AND METHODS: Cross-sectional study that undertakes a 3 years period (July 1992-March 1995) and includes 221 patients diagnosed of RA according to the 1988 criteria of the American College of Rheumatology (ACR). Association of depression levels, assessed with the Self-Rating Depression Scale of Zung-Conde, with each one of the variables was evaluated using chi 2 tests (p < 0.05). A multivariate analysis type Automatic Interaction Detection (AID), based on the statistic r2, was applied to determine patient's profile with RA and depression. RESULTS: Depressive level was identified in 33.48% of patients. Odds ratio (OR) between "not depressive" and "depressive" levels was from 20.35 with 95% CI: 8.87-47.88 (p < 0.00001). Association was found with the variables sex (p < 0.0001), profession (p = 0.02), weight and height (p < 0.0001 in both variables), Ritchie index (p < 0.004), number of painful joints (p = 0.002), morning stiffness (p = 0.049) and secondary effects of the treatment (p = 0.034). Sex was the variable that most influenced in depressive level (p < 0.00001). In females group, the factor mainly related with depression was the number of painful joints (p < 0.0002) while in males, it was the self-rating pain valuation with a Likert scale (p < 0.0001). CONCLUSIONS: RA could causes depression in the patients. The factor with highest influence in the depression of these patients was the sex. The most influential factor in the females was the number of painful joints, while in the males was the self-rating of pain.     

Low serum vitamin D metabolites in women with rheumatoid arthritis

The aim of the study was to examine the opinions of psychiatric patients regarding the aims of their care and to compare these to the aims recorded by the nursing staff on the treatment plan forms. Attention was also paid to the reasons quoted by the patients for the given helping methods and their opinions on factors which promote or hamper treatment. The basic group consisted of patients who had been treated at the Department of Psychiatry in the University Hospital District of Northern Ostrobothnia for at least two weeks. The group was divided into two parts: 1) patients treated in a close ward and 2) those in an open ward. Thirty-one patients of each kind were selected by random sampling and interviewed using five open questions which concerned the aims of the treatment, their grounds for participating in the treatment concerned and factors promoting or hampering treatment. The notes on the aims of the treatment made by the nursing staff were gathered from the treatment plan forms for the patients in question. The data were analyzed by content analysis. The primary finding was that there are still discrepancies between the aims recorded in the course of treatment and patient's own opinions. The results indicate that the patients regarded social interaction as the primary reason for seeking treatment, followed by therapeutic interaction and normative factors in the ward. Factors considered to promote helping were therapeutic interaction, medical treatment, self realization and social interaction, whereas the detrimental factors were related to the patients themselves, their individual needs, the environment, the therapeutic community or the medication provided.     

Hypothalamo-pituitary-thyroid system in patients with rheumatoid arthritis]

OBJECTIVE: To determine the effect on the uptake of breast screening of a personalized letter from the general practitioner recommending mammography, sent to coincide with an invitation from the NHS breast screening programme. DESIGN: Randomised control trial with stratification of prognostic variables. SETTING: A group practice in Hackney, east London. SUBJECTS: 473 women invited for breast screening by the City and East London Breast Screening Service. OUTCOME MEASURE: Attendance for mammography. RESULTS: All women in the randomised trial were followed up; 134 of 236 (57%) randomly allocated to receive the prompting letter attended for mammography compared with 120 of 234 (51%) controls This difference was not significant (chi 2 = 1.43, p = 0.23) CONCLUSION: Personal recommendation by a letter prompting attendance for mammography from the general practitioner known best to women due to be screened did not improve uptake of breast screening in this east London practice. Other strategies are needed to increase uptake of mammography in inner cities.     

Cementless hip prosthesis in patients with rheumatoid arthritis

A recent study conducted in Sweden reported that 1) leukemia risk in children who lived near 220 or 400 kV electric-power transmission lines was associated with calculated historical magnetic field levels; 2) children living within a distance of 50 m of transmission lines had an elevated risk of leukemia; and 3) there was no association between leukemia and residential magnetic fields measured many years after diagnosis. Subsequently, these investigators found through logistic regression analysis that disease was more strongly associated with calculated historical fields than with distance. Since the calculated historical fields in that study depended predominantly on distance and transmission-line load current, the logistic regression results suggest that historical load current plays an important role in the epidemiological results. Thus, we studied hourly 1974 load-current data for six transmission lines, and we examined 1958-1985 annual load-current data for 112 transmission lines. Most lines exhibited marked diurnal load-current rhythms during 1974, and all six showed systematic weekday-weekend differences. During 1958-1985, average loadings of Swedish 220 and 400 kV lines increased by about 1.3% year. Predictive-value and kappa-statistic analyses indicated that Swedish transmission-line load currents were not stable over long periods, so that contemporaneous load current (or a contemporary magnetic field measurement) was not a good surrogate for historical load current (or historical magnetic fields). The results provide a potential explanation of the failure of the Swedish Study to find an association between leukemia and contemporaneous magnetic field levels measured many years after the etiologic period, and suggest that the inclusion of load-current data could significantly improve the quality of historical field calculations.