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Morphological evidence that activated polymorphs circulate in the peripheral blood of patients with rheumatoid
D A McCarthy1, J Bernhagen, M J Taylor
1School of Biological Sciences, Queen Mary and Westfield College, London, UK.
Abstract:
Purified peripheral blood polymorphonuclear leucocytes (PMNs) from patients with rheumatoid arthritis (RA) have been found to differ from purified PMNs from normal subjects in ways that are consistent with their prior activation. However, it is currently contentious whether activated PMNs really circulate in patients with RA, or whether they are produced as an in vitro artefact of purification. Recently developed rapid leucocyte fixation and preparation technique showed that the proportion of polarised (activated) PMNs (36.9 (24.7)%, mean (SD); n = 31) was increased relative to that in control subjects (8.1 (5.6)%; n = 12). Serum cytidine deaminase levels, a biochemical marker of PMN lysis, were also increased in patients with RA (11.59 (7.26) U/ml) compared with those in controls (6.82 (3.78) U/ml), but the proportion of polarised PMNs and the levels of cytidine deaminase activity were unrelated to clinical assessments of inflammatory disease activity. Twelve patients who were not receiving drugs or who were receiving only non-steroidal anti-inflammatory drugs (NSAIDs) had more polarised PMNs than 19 patients receiving second line treatment in addition to NSAIDs (patients receiving NSAIDs, 49.6 (25.9)%; patients receiving second line treatment, 27.5 (21.1)%). Fluorescence activated cytometric analysis of CR1 and CR3 expression on PMNs from a randomly selected subgroup of patients with RA showed that the serum level of cytidine deaminase activity was correlated positively with the expression of CR1 (the C3b receptor) on the cell surface and that the proportion of polarised PMNs was positively correlated with the expression of CR3 (or CD11b/CD18), the iC3b receptor that is upregulated on activation. It is suggested that the polarised PMNs which circulate in blood samples from patients with RA represent cells which have been activated but not yet marginated, or activated cells which have marginated but subsequently returned to the circulating pool.
Insights
Activated polymorphonuclear leucocytes (PMNs) are found in rheumatoid arthritis (RA) patients. These activated PMNs, identified by their polarized shape and specific receptor expression, may indicate disease activity not linked to clinical measures.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Peripheral blood polymorphonuclear leucocytes (PMNs) in rheumatoid arthritis (RA) patients show signs of prior activation.
- It remains debated whether these activated PMNs are truly circulating or an artifact of laboratory processing.
Purpose of the Study:
- To investigate the presence and characteristics of activated PMNs in RA patients.
- To determine if PMN activation correlates with disease activity or treatment in RA.
Main Methods:
- Utilized a rapid leucocyte fixation and preparation technique to assess PMN polarization.
- Measured serum cytidine deaminase levels as a marker of PMN lysis.
- Analyzed CR1 and CR3 receptor expression on PMNs using fluorescence-activated cytometry.
Main Results:
- A significantly higher proportion of polarized (activated) PMNs was observed in RA patients compared to controls.
- Serum cytidine deaminase levels were elevated in RA patients, correlating with CR1 expression.
- The proportion of polarized PMNs correlated with CR3 expression, a marker of PMN activation.
- Higher PMN polarization was seen in patients not on second-line treatment compared to those on it.
- PMN polarization and cytidine deaminase levels were not correlated with clinical inflammatory disease activity.
Conclusions:
- Circulating polarized PMNs in RA patients likely represent activated cells that have not yet marginated or have returned to circulation after margination.
- PMN activation markers (polarization, cytidine deaminase, CR1/CR3 expression) are present in RA but do not correlate with clinical disease activity.
- Findings suggest a potential role for PMN activation in RA pathogenesis, independent of current clinical assessments.