Serum ferritin and free erythrocyte protoporphyrin in rheumatoid arthritis

Summary In this prospective study 20 newly diagnosed patients with definite or classical rheumatoid arthritis were followed with serial measurements of serum ferritin and erythrocyte-free protoporphyrin at the beginning of the trial and at 3 and 6 months. The values were correlated with clinical disease activity ad with various laboratory parameters. It was shown that free erythrocyte protoporphyrin has a constant negative correlation with erythrocyte haemoglobin concentration independent of disease activity, while serum ferritin behaves like an acute phase protein. Initial serum ferritin or free erythrocyte protoporphyrin values or their early changes appeared to have no prognostic value as evaluated by the development of new erosions or by the response of the patient to the therapy.     

Serum sclerostin levels in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune disease that may lead to joint destruction and disability. Wingless (Wnt) pathway is involved in bone formation and has been found to contribute to bone loss in RA. Sclerostin is a key molecule in Wnt pathway.ObjectiveTo study the serum levels of sclerostin in rheumatoid arthritis patients and to study its association with radiological changes.MethodsForty-five patients with RA and 45 age and gender matched healthy controls were enrolled. Serum sclerostin was measured by ELISA. Modified version of Larsen score was used to assess joint damage in radiographs and Magnetic resonance imaging (MRI) of wrist and hand was assessed for synovitis and bone erosion.ResultsSerum sclerostin levels were higher in patients with RA as compared to controls (p < 0.01). Serum sclerostin levels correlated with ESR (r = 0.655), CRP(r = 0.623), modified DAS 28 (r = 0.711), MRI synovitis (r = 0.802) and MRI erosion score (r = 0.832).ConclusionIncreased serum levels of sclerostin may play a role in joint damage and bone erosion in RA.     

Serum calcium levels in rheumatoid arthritis.

Total and corrected (for albumin) serum calcium levels were investigated in a cross-sectional study of 394 patients with rheumatoid arthritis, 4490 healthy subjects, and 2609 inpatients at a district general hospital. Patients with rheumatoid arthritis had lower mean clacium levels than the healthy subject (p less than 0.001), but had similar levels to inpatients at the district general hospital. Thirty-eight inpatients with rheumatoid arthritis at a hospital for rheumatic diseases had lower mean corrected and total calcium levels than all other groups (p less than 0.01). Corrected or total calcium levels higher than 2.60 mmol/l or corrected calcium levels lower than 2.20 mmol/l were uncommon in the patients with rheumatoid arthritis. A longitudinal study of serum calcium levels in 17 patients with rheumatoid arthritis over 6-48 months showed considerable temporal variation in total and corrected calcium levels. Transient hypercalcaemia and hypocalcaemia occurred occasionally, but for most of the time calcium levels were normal. Changes in calcium levels were not related to changes in clinical, haematological, or immunological parameters of disease activity. Mean serum calcium levels are lower in disease than health; this occurs in RA as well as other diseases.     

Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia

Serum immunoreactive erythropoietin (EP) levels were measured in 116 patients with rheumatoid arthritis (RA) and 20 control patients with iron deficiency anemia. Serum EP levels were significantly higher in the 46 anemic RA patients than in the 70 nonanemic RA patients (mean ± 1 SD 31.0 ± 19.8 mU/ml versus 16.8 ± 12.4 mU/ml; P < 0.0001). Furthermore, although a significant inverse correlation between the serum EP level and the hemoglobin value was present in the anemic RA patients (r = −0.57, P < 0.0001), the regression coefficient describing the relationship between serum EP and hemoglobin was significantly lower for the anemic RA patients than for patients with iron deficiency anemia (F = 6.01, P < 0.025).     

Serum ferritin as indicator of iron responsive anaemia in patients with rheumatoid arthritis.

In order to test the hypothesis that serum ferritin below 60 micrograms/l is a good indicator of iron deficiency in patients with rheumatoid arthritis peroral iron was given to 67 patients with active rheumatoid arthritis over a three month period. A rise in haemoglobin concentration was taken as evidence of iron responsive anaemia. In anaemic patients serum ferritin below 60 micrograms/l was a good indicator of iron responsive anaemia, with a predictive value of 83%. Although high plasma transferrin and low mean cell volume showed similar predictive values, more patients with iron deficiency anaemia could be diagnosed by serum ferritin measurements than by other conventional blood tests. In contrast, the predictive value of serum ferritin above 60 micrograms/l was low (50%). The test was of no predictive value in non-anaemic patients. In patients with anaemia and active rheumatoid arthritis serum ferritin is the best blood test currently available for the prediction of iron responsive anaemia.     

Serum and red cell ferritin content in the evaluation of iron status in rheumatoid arthritis

We measured the basic (spleen type) ferritin content in the serum and red cells of 72 patients with rheumatoid arthritis in order to evaluate their significance in detecting true iron deficiency that may coexist with an altered metabolism of iron. Sixteen patients had no anaemia, and their serum and red cell ferritin contents were within the normal range (serum ferritin 16 to 286 micrograms/l; red cell ferritin, 5 to 44 ag/cell). Twenty patients had normocytic normochromic anaemia, and 36 patients had microcytic hypochromic anaemia. In these anaemic patients, the serum ferritin level ranged from 0 to 12 micrograms/l in 4, 13 to 55 micrograms/l in 19, 56 to 110 micrograms/l in 16, and exceeded 110 micrograms/l in 17 patients. The red cell ferritin content was subnormal (less than 5 ag/cell) in 4/20 patients in the normocytic normochromic group, and in 15/36 patients in the microcytic hypochromic group. Oral iron therapy given for 4-6 weeks to 9 patients with subnormal red cell ferritin resulted in an increase in the haemoglobin concentration; no such response was observed in patients with normal red cell ferritin content, irrespective of the serum ferritin concentrations. These observations indicate that red cell ferritin content is a more reliable index of true iron deficiency than serum ferritin concentrations in rheumatoid arthritis, and is capable of predicting the response to iron therapy.     

Relationship between serum ferritin,anemia, and disease activity in acute and chronic rheumatoid arthritis

Summary The assessment of anemia in patients with rheumatoid arthritis may be difficult, especially when iron deficiency and the anemia of chronic disease coexist. The development of a radioimmunoassay for serum ferritin concentration has aided the detection of reduced body iron stores in uncomplicated iron deficiency, but its use is compromised in clinically active rheumatoid arthritis by the tendency of serum ferritin to behave as an acute phase reactant. In this latter role it correlated well with disease activity in the patients we studied. Followed serially, serum ferritin levels fell in patients whose disease activity improved after institution of appropriate therapy. In anemic patients with clinically inactive disease, supplemental iron was associated with a significant rise in hemoglobin when compared to untreated patients. Serum ferritin levels behaved independently of hemoglobin levels. Therefore even in clinically inactive rheumatoid arthritis, serum ferritin does not accurately reflect an iron deficiency.     

Serum osteocalcin levels in rheumatoid arthritis: a marker for accelerated bone turnover in late onset rheumatoid arthritis

Levels of serum osteocalcin (OC) are increased in diseases with high bone turnover. We determined OC levels in (1) 15 patients with definite rheumatoid arthritis (RA) in early stages according to Steinbrocker's functional class FC I-II, (2) 40 patients at advanced stages (FC III-IV) and (3) 17 patients with late RA (onset at age of 65 or more). Sixty-two healthy volunteers, divided into 3 subgroups corresponding to the patients, and 19 patients with primary fibromyalgia syndrome (FMS) served as controls. All patients were included in a short term as well as a longitudinal study over one year. Mean OC levels were significantly elevated in patients with late onset RA compared with healthy controls (p = 0.037), while the OC values in early RA FC I-II and advanced RA FC III-IV did not differ significantly from the corresponding control group and the patients with FMS. The late RA group showed a positive correlation between OC and the erythrocyte sedimentation rate (ESR) (r = 0.641, p = 0.007) with a significant decrease of OC (p less than 0.01) as well as ESR (p = 0.047) over one year. We conclude increased OC levels correlate with disease activity in older patients with active RA, suggesting impaired bone turnover. This finding supports the picture of heterogeneity in RA with more late onset patients displaying "high bone turnover."     

Serum ferritin and iron uptake by peripheral blood leucocytes in patients with active rheumatoid arthritis

Summary Rheumatoid arthritis is a systemic disease in which anaemia is common. The origin of the anaemia is usually multifactorial. Iron deficiency, a defect of release of iron from the reticulo-endothelial system¹ is discussed. Ferritin content of monocytes, lymphocytes and polymorphes is found altered and mostly elevated in monocytes affected by serum iron deficiency. In all cell types iron uptake is related to transferrin saturation. Alterations against normal subjects in iron uptake, ferritin synthesis and iron incorporation into ferritin are mostly found in patients with serum iron deficiency.     

Serum leptin in rheumatoid arthritis

Leptin is a peptide hormone that has an essential role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. The role of leptin in the modulation of the immune response and inflammation has been regarded as important. In rheumatoid arthritis (RA) patients it was reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin. These features suggest that leptin may also influence the inflammatory mechanisms of arthritis in humans. In this study we assessed serum leptin levels in RA and osteoarthritis (OA) patients and found a correlation between serum leptin level and other markers as well as bone mass density changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA and 30 OA patients who constituted the control group. Serum leptin level was determined using the DRG Leptin ELISA Kit—a solid phase enzyme—linked immunosorbent assay based on the sandwich principle. The serum level of leptin in RA patients ranged from 1.8 to 81.1 ng/ml and median value was 11.2. There was a positive correlation between body mass index (BMI) of RA patients and serum level of leptin (correlation coefficients Spearman’s r = 0.81). According to correlation coefficients, serum leptin level is independent of age of RA patients, stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration as well as value of titre of the Waaler–Rose, disease activity score (DAS 28) value and presence of rheumatoid nodules. There was a negative correlation between serum leptin level and glomerular filtration rate (GFR). No correlation between the serum leptin level and T-score was found. An influence of steroid treatment on the serum leptin level was not shown. The median serum leptin level in OA patients was 9.2 ng/ml. There was a positive correlation between body mass index of OA patients and serum level of leptin (correlation coefficients Spearman’s r = 0.57). No correlation was found between serum leptin level and patient’s age, duration of disease and value of laboratory data. There were no correlations between serum leptin level and visual analogue pain scale (VAS) for the lower-limb afflicted patients as well as stage of disease according to Kellgren and Lawrence’s score in OA patients. There was a negative correlation between serum leptin level and T-score value in OA patients (r = −0.58, P < 0.05). No statistically significant differences were found between serum leptin levels for RA and OA patients.     

Serum ferritin levels in hemoglobin H disease

This study shows that hemoglobin H disease patients aged between 0.5 and 44 years, usually (27 out of 30) have normal serum ferritin levels according to age. This reconfirms that in this disease there are usually normal iron stores. However, in a few patients (3 out of 30) increased levels were found. This may be due to inappropriate iron medication, transfusions or associated idiopathic hereditary hemocromatosis gene.     

Serum levels of soluble CD44 variant isoforms are elevated in rheumatoid arthritis

Serum levels of soluble CD44 variant proteins including sequences encoded by exon v5 and exon v6 (sCD44v5, sCD44v6) were determined in patients with inflammatory rheumatic diseases: 56 with rheumatoid arthritis (RA⁺) and 31 with miscellaneous inflammatory rheumatic diseases (MIRD). There were very significantly higher serum levels of sCD44v5 and sCD44v6 in patients with RA' than in those with MIRD (RA⁺ to MIRD: sCD44v5: 81 ± 54 ng/ml to 33 ± 13 ng/ml; sCD44v6: 237 ± 124 ng/ml to 166 ± 53 ng/ml; bothP0.001). In RA⁺ elevated serum levels of sCD44v5 were correlated with the inflammatory activity of disease. In 17 patients with RA⁺ three or four follow-up measurements of sCD44v5 were performed within 6 months. The development of sCD44v5 serum levels reflected the clinical course of disease in the patients investigated.     

Serum and synovial fluid leptin levels and markers of inflammation in rheumatoid arthritis

This study was designed to investigate the serum and synovial fluid leptin levels, and inflammatory markers in rheumatoid arthritis (RA) patients. Serum and synovial fluid leptin levels were significantly higher (P > 0.05) in RA patients than control group; RA patients with moderate disease activity (DAS < 2.7) having significantly higher leptin levels (P > 0.05) than those with low disease activity (DAS < 2.7). Leukocytes and erythrocyte sedimentation rate (ESR) were found to be significantly higher in moderate disease activity RA group compared to low activity group (P > 0.05, P < 0.001, respectively). Serum leptin level is found to be independent of age and inflammatory markers. ESR is positively correlated with DAS activity and CRP values. Our finding of no correlation between leptin and BMI shows that regulation of leptinemia is complex, and leptin levels cannot be used to assess RA activity.