Stromal cell-derived factor-1
in rheumatoid arthritis
G. A. Mittal,
V. R. Joshi and
A. Deshpande
PD Hinduja Hospital and MRC, Rheumatology, Mumbai, Maharashtra, India
SIR, Stromal cell-derived factor-1
(SDF-1
) is a CXC class of chemokine with multiple cellular effects [1]. It is so named as it was first isolated from a bone-marrow stromal cell line [2]. It is an 8 kDa peptide and exists in
and ß isoforms. These are encoded by a single gene and arise by alternative splicing [3].
Rheumatoid arthritis (RA) is characterized by proliferation of synoviocytes, pannus formation and infiltration of inflammatory cells. Of these, CD4+ memory T cells play a pivotal role in the initiation and maintenance of rheumatoid synovitis. Migration of T cells to the synovium [4] and their retention in a perivascular distribution [5] is facilitated by SDF-1. SDF-1 additionally inhibits activation-induced apoptosis of T cells [4]. B-cell accumulation and formation of ectopic germinal centres is another characteristic feature of rheumatoid synovitis. This is stimulated by SDF-1 which is expressed on synovial fibroblasts [6]. SDF-1
activates fibroblast-like synoviocytes, stimulates angiogenesis and degrades cartilage matrix by stimulating release of matrix metalloprotease 3 from human chondrocytes [7]. These actions suggest that SDF-1 may play a role in the pathogenesis of RA. We have estimated the levels of SDF-1
in plasma of 49 patients with RA and correlated these with measures of disease activity. These results are discussed in this communication.
Forty-nine consecutive patients with RA were studied. All the patients fulfilled the 1987 American College of Rheumatology classification criteria for RA [8]. The median age of the patients was 46 yr (range 1976). Forty-four were females. Thirty-four were seropositive. The median duration of RA was 5.25 yr (range 0.2520). In all, 35 patients were receiving disease-modifying anti-rheumatic drugs (DMARDs; methotrexate n = 30, chloroquine n = 10 and sulphasalazine n = 9). Eight patients were receiving prednisolone (<10 mg/day). Plasma samples were collected from the patients and from 30 normal healthy individuals. Activities of daily living were measured by the Indian Health Assessment Questionnaire (HAQ) validated for Indian patients [9]. SDF-1
levels were estimated by enzyme-linked immunosorbent assay (kit supplied by R & D Systems, Minneapolis, MN, USA). Student's unpaired t-test was used for statistical analysis.
The relevant clinical and laboratory parameters [expressed as median (range)] were as follows: tender joint count 3 (028), swollen joint count 3 (014), early morning stiffness 15 min (0360), Indian HAQ 1 (02.42), disease activity score 4.55 (2.257.94) [10], haemoglobin 11.6 (8.415) g/dl, erythrocyte sedimentation rate 50 (4135) mm/h, and Sharp's modified score 26 (0178). Mean±S.D. levels of plasma SDF-1
in RA were significantly higher than in normal individuals (3731.58±553.58 and 3354.21±719.15 pg/ml, respectively, P<0.01) (Fig. 1
). When the levels of SDF-1
were compared between patients having active (Disease Activity Score, DAS >5) and inactive disease (DAS <5), there was no statistically significant difference (P = 0.08). There was no correlation between plasma SDF-1
levels and clinical or laboratory measures of activity or damage regarding tender joint count, swollen joint count, early morning stiffness, Indian HAQ, haemoglobin, erythrocyte sedimentation rate and Sharp's modified score (data not shown).

View larger version (63K):
[in this window]
[in a new window]
|
FIG. 1. Significantly elevated levels of plasma SDF-1 from patients with RA compared with healthy controls (P < 0.01). Horizontal bars indicate mean.
|
|
In an earlier study we found that synovial fluid levels of SDF-1
in nine patients with recent-onset RA (<12 months disease duration), not treated with DMARDs, were only marginally higher than those in osteoarthritis (OA) (P = 0.62) [11]. This may be attributed to small sample size. However, Kanbe et al. [7] have reported significantly higher synovial fluid concentrations of SDF-1 in patients with RA than in patients with OA and normal controls. The significantly elevated levels in plasma samples of patients with RA in the present study support the contention that SDF-1
may be playing a role in the pathogenesis of RA. One can only speculate the reasons for lack of correlation between plasma SDF-1
and parameters of disease activity and damage. These could be due to variable disease activity, disease duration or sample size or more likely the effect of drug therapy. Studies of patients with early RA with no history of DMARD therapy may help to clarify the matter.
Conflict of interest
The authors have declared no conflicts of interest.
Notes
Correspondence to: V. R. Joshi. E-mail: dr_vjoshi{at}rediffmail.com 
References
- Pulsatelli L, Dolzani P, Piacentini A et al. Chemokine production by human chondrocytes. J Rheumatol 1999;26:19922001.[ISI][Medline]
- Jo DY, Rafii S, Hamada T, Moore MA. Chemotaxis of primitive hematopoietic cells in response to stromal cell-derived factor-1. J Clin Invest 2000;105:10111.[Abstract/Free Full Text]
- Shirozu M, Nakano T, Inazawa J et al. Structure and chromosomal localization of the human stromal cell-derived factor (SDF1) gene. Genomics 1995;28:495500.[CrossRef][ISI][Medline]
- Nanki T, Hayashida K, El-Gabalawy HS et al. Stromal cell-derived factor-1-CXC chemokine receptor 4 interactions play a central role in CD4+ T cell accumulation in rheumatoid arthritis synovium. J Immunol 2000;165:65908.[Abstract/Free Full Text]
- Buckley CD, Amft N, Bradfield PF et al. Persistent induction of the chemokine receptor CXCR4 by TGF-ß1 on synovial T cells contributes to their accumulation within the rheumatoid synovium. J Immunol 2000;165:34239.[Abstract/Free Full Text]
- Burger JA, Zvaifler NJ, Tsukada N, Firestein GS, Kipps TJ. Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived factor-1-and CD106(VCAM-1)-dependent mechanism. J Clin Invest 2001;107:30515.[Abstract/Free Full Text]
- Kanbe K, Takagishi K, Chen Q. Stimulation of matrix metalloprotease 3 release from human chondrocytes by the interaction of stromal cell-derived factor 1 and CXC chemokine receptor 4. Arthritis Rheum 2002;46:1307.[CrossRef][ISI][Medline]
- Arnett FC, Edworthy SM, Bloch DA et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:31524.[ISI][Medline]
- Kumar A, Pandhi A, Singh R. Validation of an Indian version of health assessment questionnaire (HAQ) in patients with rheumatoid arthritis [Abstract]. Paper presented at 17th Annual Conference of Indian Rheumatology Association, 6 to 9 December 2001, Chandigarh.
- Prevoo ML, van't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38:448.[ISI][Medline]
- Mittal G, Joshi VR. Study of cell derived factor 1
in synovial fluid in early rheumatoid arthritis. Comments on the article by Knabe et al. Arthritis Rheum 2003;48:271475.
Accepted 3 December 2002