Are the C-reactive protein values and erythrocyte sedimentation rate equivalent when estimating the 28-joint disease activity score in rheumatoid arthritis?

UNLABELLED: A formula for calculating disease activity score with 28 joint counts (DAS28) with C-reactive protein (CRP) instead of the erythrocyte sedimentation rate (ESR) has been proposed. OBJECTIVE: Here we analyze the factors that contribute to the differences in the DAS28 when calculated using either the ESR (DAS28-ESR) or the CRP values (DAS28-CRP). METHODS: We analyzed the data from 587 visits made by 220 patients with early arthritis. The age at the onset of the disease was 51+/-16 years old and 76.3% of the patients were women. The disease evolution at the first visit was 5 months and at each visit information related to several variables was collected, including that necessary to calculate the DAS28-ESR and DAS28-CRP. We defined a new variable DIFDAS=DAS28-ESR-DAS28-CRP to analyze which independent variables account for differences between the two indexes. RESULTS: There was a correlation between the two indexes of 0.91 (p<0.0001), although the DAS28-ESR value obtained was higher than that of DAS28-CRP at approximately 90% of the visits. Significantly, the difference between both indexes was higher than 0.6 in 44% of the visits studied. A multivariate analysis showed that female gender and disease duration were associated with the higher values obtained for DAS28-ESR when compared to those of DAS28-CRP. CONCLUSION: Our data show that DAS28-ESR and DAS28-CRP are not fully equivalent, because the former usually produces higher values. This finding is particularly relevant in females and patients with a long disease duration.

Regulation of ICAM-3 (CD50) membrane expression on human neutrophils through a proteolytic shedding mechanism.

The regulation of the cell surface expression of ICAM-3 (CD50) was investigated in human neutrophils. Immunofluorescence flow cytometry analysis revealed a remarkable and very rapid down-regulation of the ICAM-3 cell surface expression upon neutrophil activation with stimulating agents such as phorbol myristate acetate (PMA) or calcium ionophore. A similar low expression of ICAM-3 was observed on neutrophils from patients undergoing hemodialysis with cell-activating cellulosic membranes. Internalization assays with 125I-labeled anti-ICAM-3 monoclonal antibody (mAb) suggested that ICAM-3-down-regulation was due to antigen release from the cell surface towards the outer milieu, rather than to antigen internalization. Immunoprecipitation studies confirmed this down-regulatory effect, and revealed the presence of ICAM-3 in cell-free supernatants from activated neutrophils. Furthermore, the presence of a soluble form of ICAM-3 with a range of concentrations of 0-296 ng/ml in the plasma from healthy human volunteers was detected by using a two-site mAb radioimmunoassay. A proteolytic mechanism likely accounts for this process since protease inhibitors virtually abrogated the PMA-induced down-regulation of ICAM-3. Functional studies showed that anti-ICAM-3 mAb were able to trigger homotypic neutrophil aggregation both before and after ICAM-3 down-regulation, indicating that the fraction of ICAM-3 molecules remaining on the neutrophil surface upon activation are still capable of sustaining cell adhesion. In contrast, the loss of L-selectin (CD62L) on activated neutrophils was almost complete, thus leading to an impairment of L-selectin-mediated neutrophil-endothelial cell adhesion. These results indicate that ICAM-3 is released to the medium upon neutrophil stimulation and that both ICAM-3 and L-selectin have a role in the neutrophil adhesive phenomena.

Expression of L-selectin, CD43, and CD44 in synovial fluid neutrophils from patients with inflammatory joint diseases. Evidence for a soluble form of L-selectin in synovial fluid.

OBJECTIVE: To study the expression of L-selectin, CD43, and CD44 on peripheral blood (PB) and synovial fluid (SF) neutrophils from patients with inflammatory joint diseases, and to investigate the presence of soluble L-selectin in both SF and plasma from patients with acute and chronic arthritis. METHODS: PB and SF neutrophils were isolated from 13 patients with rheumatoid arthritis (RA) and 17 patients with various inflammatory joint diseases other than RA. Expression of L-selectin, CD43, CD44, CD11a, and CD11b was determined in both unstimulated and in vitro-activated cells by immunofluorescence flow cytometry. Soluble L-selectin levels were estimated in SF and plasma by a semiquantitative radioimmunoassay. RESULTS: Neutrophils from SF showed diminished expression of L-selectin compared with PB neutrophils; CD43 expression and CD44 expression were decreased in SF neutrophils from most patients. In contrast, SF neutrophils exhibited significantly increased expression of CD11b, to an extent similar to that seen with in vitro-activated PB neutrophils. Soluble L-selectin was detected at similar levels in SF and PB. CONCLUSION: The phenotypic profile of SF neutrophils (low levels of L-selectin, CD43, and CD44, and high levels of CD11b) from most patients with RA or other inflammatory joint conditions resembles that observed in in vitro-activated neutrophils. Our results suggest that SF neutrophils are activated to a similar degree in inflammatory joint diseases with different pathogenic mechanisms.

VLA family in rheumatoid arthritis: evidence for in vivo regulated adhesion of synovial fluid T cells to fibronectin through VLA-5 integrin.

Adhesion of T cells to extracellular matrix (ECM) proteins through VLA integrin receptors is crucial for lymphocyte trafficking, tissue localization and inflammatory function. We have investigated the expression of different VLA integrins (VLA-1-5) on peripheral blood (PB) and synovial fluid (SF) T lymphocytes from patients with rheumatoid arthritis (RA). Their expression on different cell types from synovial membrane (SM) is also reported. The role of VLA-4 fibronectin (FN) receptors in the interaction of activated SF T cells from RA patients with a 38-kD fragment of FN has been previously demonstrated. Here we have focused functional studies on VLA-5 as an alternative FN receptor for RA T cells. A significant higher proportion of SF T cells were able to bind to an 80-kD fragment of FN, containing the Arg-Gly-Asp (RGD) cell binding site, compared with PB T cells. This attachment was almost completely inhibited by anti-VLA-5 MoAbs as well as by RGD peptides. This enhanced capability by SF T cells appears to be independent of the level of the surface expression of the receptor and correlates better with their activation state as determined by the expression of the activation molecule AIM (CD69). The evidence for the expression of VLA heterodimers on both SF and SM cells from RA patients suggests the possible implication of ECM proteins in mediating and perpetuating inflammation in vivo.

Upregulated expression and function of VLA-4 fibronectin receptors on human activated T cells in rheumatoid arthritis.

The VLA-4 (CD49d/CD29) integrin is a cell surface receptor involved in the interaction of lymphoid cells with both extracellular matrix (ECM) and endothelial cells. We have investigated the expression and function of VLA-4 fibronectin (FN) receptors on T cells localized in the inflammed synovium of patients with rheumatoid arthritis (RA). A high proportion of T cells in both synovial membrane (SM) and synovial fluid (SF) expressed the activation antigens AIM (CD69) and gp95/85 (Ea2) as well as an increased number of VLA-4 alpha and beta 1 adhesion molecules, as compared with peripheral blood (PB) T cells from the same patients. Furthermore, the majority of these activated SF T cells were able to adhere to a 38-kD FN proteolytic fragment containing the connecting segment-1 (CS-1) specifically through VLA-4 receptors, whereas a significantly lower proportion of PB T cells displayed this capacity. Therefore, our results show that activated T cells selectively localize at sites of tissue injury in RA disease and provide evidence for the in vivo regulation of the expression and function of the VLA-4 integrin. This regulatory mechanism may enable T cells either to facilitate migration or to persist at sites of inflammation.

Systemic lupus erythematosus and tetrasomy-X.

An 18-year-old woman with tetrasomy-X (48,XXXX karyotype) who developed systemic lupus erythematosus is described. This is, to our knowledge, the first recorded case of this association. The occurrence of autoimmune disorders in patients with chromosomal aberrations is discussed.