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1.  CpG-DNA derived from sera in systemic lupus erythematosus enhances ICAM-1 expression on endothelial cells 
Annals of the Rheumatic Diseases  2001;60(7):685-689.
OBJECTIVE—To examine the effect of transfection of oligodeoxynucleotides (ODNs) containing a CpG motif (CpG-ODN), of which the sequence was derived from circulating DNA in the sera of patients with systemic lupus erythematosus (SLE), on the expression of intercellular adhesion molecule-1 (ICAM-1) and synthesis of mRNA for proinflammatory cytokines and ICAM-1 in human umbilical vein endothelial cells (EC).
METHODS—A CpG-ODN or a control analogue, GpC-ODN, was transfected into EC. ICAM-1 expression was examined by flow cytometry, and expression of mRNA in EC encoding interleukin 1 (IL1), IL6, IL8, tumour necrosis factor α (TNFα), interferon γ (IFNγ), and ICAM-1 was examined by semiquantitative reverse transcriptase-polymerase chain reaction.
RESULTS—The CpG-ODN augmented the expression of ICAM-1 on EC determined by flow cytometry and increased mRNA levels of IL6, IL8, TNFα, IFNγ, and ICAM-1, but the GpC-ODN did not.
CONCLUSION—Synthesised DNA, with a sequence corresponding to that of the fragment containing the CpG motif, in sera of patients with SLE was found to enhance ICAM-1 expression on EC, suggesting the participation of circulating DNA fragments in the pathogenesis of vasculitis in SLE.


doi:10.1136/ard.60.7.685
PMCID: PMC1753728  PMID: 11406523
2.  Characterisation of T cell clonotypes that accumulated in multiple joints of patients with rheumatoid arthritis 
Annals of the Rheumatic Diseases  1999;58(9):546-553.
OBJECTIVE—To investigate whether identical T cell clonotypes accumulate in multiple rheumatoid joints, the clonality of T cells that had infiltrated into synovial tissue (ST) samples simultaneously obtained from multiple joints of patients with rheumatoid arthritis (RA) was analysed.
METHODS—T cell receptor (TCR) β gene transcripts, amplified by reverse transcription-polymerase chain reaction from ST and peripheral blood lymphocytes of five RA patients, were subjected to single strand conformation polymorphism analysis and DNA sequencing.
RESULTS—Approximately 40% of accumulated T cell clonotypes found in one joint of a patient were found in multiple joints in the same patient. Furthermore, identical amino acid sequences were found in TCR β junctional regions of these clonotypes from different patients with at least one HLA molecule match.
CONCLUSIONS—The T cell clonotypes accumulating in multiple rheumatoid joints may be involved in the perpetuation of polyarthritis by reacting to antigens common to these multiple joints.


PMCID: PMC1752942  PMID: 10460187
3.  Complement activating properties of monoreactive and polyreactive IgM rheumatoid factors. 
Annals of the Rheumatic Diseases  1993;52(11):795-800.
OBJECTIVES--To estimate the complement activating properties of monoclonal, monoreactive, and polyreactive IgM rheumatoid factors derived from Epstein-Barr virus transformed B cells isolated from peripheral blood and synovial tissue of patients with rheumatoid arthritis (RA). METHODS--An enzyme linked immunosorbent assay (ELISA) was used to measure the activation of the classical pathway of complement by monoclonal IgM rheumatoid factor. Monoclonal IgM rheumatoid factor was bound to IgG Fc adsorbed onto microtitre plates and then reacted with diluted normal human serum as a source of complement. The activation and binding of C4 were measured with F(ab')2 antibody to human C4. The complement activating property of IgM rheumatoid factor bound to IgG Fc was tentatively expressed as the ratio of the amount of bound C4 to the amount of bound IgM rheumatoid factor. RESULTS--The complement activating property of monoreactive IgM rheumatoid factor was shown to be about three times higher than that of polyreactive IgM rheumatoid factor. CONCLUSIONS--Monoreactive IgM rheumatoid factor with the higher complement activating property would result in a greater degree of complement dependent inflammation and might have a more important pathogenic role in RA than polyreactive IgM rheumatoid factor.
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PMCID: PMC1005191  PMID: 8250611
4.  Risk factors in the pregnancy of patients with systemic lupus erythematosus: association of hypocomplementaemia with poor prognosis. 
Annals of the Rheumatic Diseases  1992;51(5):619-623.
Fetal wastage is still high in the pregnancies of patients with systemic lupus erythematosus (SLE). We examined retrospectively the cases of 38 patients with inactive SLE in whom pregnancy was either desired or had already been obtained. The prevalence of antiphospholipid antibodies in the group with fetal loss was high. The antibodies were, however, also detected in five of 14 patients who had had a live birth. It was noted that low levels of serum complement activity (CH50 less than 25 U/ml) occurred in five of six patients with fetal loss, but in only two of 22 with a live birth. Serial studies also confirmed a close association between decreased serum complement activity and poor fetal prognosis in lupus pregnancy. Treatment with increased doses of prednisolone may help to achieve successful live births. Thus hypocomplementaemia may be associated with a worse prognosis for the fetus in the pregnancies of some patients with SLE in remission.
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PMCID: PMC1005693  PMID: 1616326

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