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Ann Rheum Dis. Dec 2006; 65(12): 1671–1672.
PMCID: PMC1798478

Increased expression of macrophage colony‐stimulating factor in ankylosing spondylitis and rheumatoid arthritis

Increasing evidence suggest that macrophage colony‐stimulating factor (M‐CSF) plays a part in rheumatoid arthritis, but few studies have focused on its role in ankylosing spondylitis. This study aimed at investigating M‐CSF expression and its clinical significance in active ankylosing spondylitis and rheumatoid arthritis.

Sandwich ELISA was used to measure serum M‐CSF levels in 12 active patients with ankylosing spondylitis (Bath Ankylosing Spondylitis Disease Activity Index of [gt-or-equal, slanted]3)1 and 12 active patients with rheumatoid arthritis.2 Eleven serum samples of healthy volunteers were examined as controls. We also examined M‐CSF mRNA expression in peripheral blood mononuclear cells (PBMCs) using real‐time reverse transcription‐polymerase chain reaction. The relative fold increase in M‐CSF mRNA expression in patient groups was determined by 2−ΔΔC.3 Considering that tumour necrosis factor (TNF) α and interleukin (IL) 1α have the ability to induce M‐CSF,4 we also investigated their levels and correlations with M‐CSF. Sensitivities of ELISA kits are as follows: M‐CSF, 9 pg/ml (Minneapolis, Minnesota, USA); TNFα, 5 pg/ml (Beckman, Immunotech, Marseille, France); and IL1α, 1.5 pg/ml (Cayman Chemical Company, Michigan, USA).

The mean (standard deviation (SD)) concentrations of serum M‐CSF were significantly increased in patients with ankylosing spondylitis (2234 (2154) pg/ml; p<0.001) and in patients with rheumatoid arthritis (2148 (1803) pg/ml, p<0.001) as compared with that in controls (232 (46) pg/ml). A total of 7 of the 12 patients with ankylosing spondylitis and 10 of the 12 patients with rheumatoid arthritis had increased C reactive protein concentrations (>1 mg/dl). As table 11 shows, the serum level of M‐CSF significantly correlated with Bath Ankylosing Spondylitis Disease Activity Index, erythrocyte sedimentation rate and serum immunoglobulin A (IgA) in the ankylosing spondylitis group, as well as with disease activity scores, C reactive protein and serum albumin in the rheumatoid arthritis group.

Table thumbnail
Table 1 The correlation coefficients between serum macrophage colony‐stimulating factor levels and disease activity variables

M‐CSF mRNA expression in PBMCs is 5.6‐fold and 7.3‐fold increased in patients with ankylosing spondylitis and rheumatoid arthritis, respectively, when compared with that in controls (fig 11).

figure ar54874.f1
Figure 1 Change (Δ) CT of each subject in ankylosing spondylitis (AS), rheumatoid arthritis (RA) and control (con) groups. The relative increase in macrophage colony‐stimulating factor mRNA (ΔCT) was determined by this ...

The mean (SD) serum TNFα concentration was significantly increased in patients with rheumatoid arthritis (335 (388) pg/ml; p<0.01) as compared with that in controls (12 (15) pg/ml), whereas no significant difference was found between patients with ankylosing spondylitis (34 (60) pg/ml) and controls. The mean (SD) levels of IL1α were significantly increased in both patients with ankylosing spondylitis and rheumatoid arthritis (110 (92) and 120 (78) pg/ml, respectively; both p<0.01) when compared with that in controls (3 (9) pg/ml). However, we failed to find any significant correlation between M‐CSF and TNFα (r = 0.48) in patients with rheumatoid arthritis, or between M‐CSF and IL1α (r = 0.39 and 0.11, respectively) in patients with ankylosing spondylitis and rheumatoid arthritis.

Our results showed an increased serum level of M‐CSF in patients with ankylosing spondylitis, which is consistent with earlier studies suggesting that macrophages are crucial for inflammatory responses in patients with ankylosing spondylitis.5 Yang et al6 have studied M‐CSF in patients with ankylosing spondylitis, but they were unable to find a significant difference in the serum M‐CSF level between patients with ankylosing spondylitis and controls. Koth7 reported that M‐CSF can exist in several forms and different target sites used in different ELISA kits should be considered to explain different findings. Notably, the assay buffers from R&D Systems (Minneapolis, Minnesota, USA) we used are designed to prevent any interactions that could potentially interfere. In our data, M‐CSF mRNA expression in PBMCs was significantly increased in patients with ankylosing spondylitis and rheumatoid arthritis, suggesting that PBMCs may play a part in increased circulating M‐CSF levels, although inflammatory sites, such as sacroiliac joints, and involved peripheral joints may also contribute to increased serum M‐CSF. Additionally, significant correlations between M‐CSF and activity index in patients with ankylosing spondylitis and rheumatoid arthritis also highlight the potential role of M‐CSF in evaluating the activity of the two diseases.

Footnotes

Competing interests: None declared.

References

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5. Braun J, Bollow M, Neure L, Seipelt E, Seyrekbasan F, Herbst H. et al Using of immunohistological and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 1995. 38499–505.505 [PubMed]
6. Yang C, Gu J, Rihl M, Baeten D, Huang F, Zhao M. et al Serum levels of matrix metalloproteinase 3 and macrophage colony‐stimulating factor 1 correlate with disease activity in ankylosing spondylitis. Arthritis Rheum 2004. 51691–699.699 [PubMed]
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