Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation

Gaston, Hill; Strober, Samuel; Solovera, J. J.; Gandour, Donna; Lane, Nancy E.; Schurman, David J.; Hoppe, Richard T.; Chin, Richard; Eugui, Elsie M.; Vaughan, John H.; Allison, A. C.

doi:10.1002/art.1780310104

Cited by 31 publications

(6 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Any of these possibilities might contribute to the prolonged depletion of T cells from peripheral blood, which is a feature of patients with RA after lymphocytotoxic treatment. [19][20][21][22][23] Why some patients have more abundant T cell infiltration at baseline and respond favourably is not known. It may be attributed either to differences in the pathogenesis or in fluctuations of disease state.…”

Section: Discussionmentioning

confidence: 99%

“…Seven patients with RA (mean age 49 years, range 35-55; disease duration 12 years, range [7][8][9][10][11][12][13][14][15][16][17][18][19][20] were treated at Leiden University Medical Centre (LUMC) with HDC + ASCT as part of a multicentre phase I/II trial. 8 The protocol was approved by the LUMC medical ethical committee and the patients gave written informed consent to undergo arthroscopic procedures as described below.…”

Section: Patientsmentioning

confidence: 99%

See 1 more Smart Citation

Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

Verburg

Flierman²,

Sont

et al. 2005

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

Objective: To determine clinical and immunological correlates of high dose chemotherapy (HDC) + autologous stem cell transplantation (ASCT) in patients with severe rheumatoid arthritis (RA), refractory to conventional treatment. Methods: Serial samples of peripheral blood and synovial tissue were obtained from seven patients with RA treated with HDC and autologous peripheral blood grafts enriched for CD34+ cells. Disease activity was assessed with the Disease Activity Score (DAS), serum concentrations of C reactive protein (CRP), and human immunoglobulin (HIg) scans, and the extent of immunoablation was determined by immunophenotyping of peripheral blood mononuclear cells, and immunohistochemistry and double immunofluorescence of synovium. Results: Clinical responders (n = 5) had a larger number of cells at baseline expressing CD3, CD4, CD27, CD45RA, CD45RB, and CD45RO in synovium (p,0.05), higher activity on HIg scans (p = 0.08), and a trend towards higher concentrations of CRP in serum than non-responders (n = 2). Subsequent remissions and relapses in responders paralleled reduction and re-expression, respectively, of T cell markers. A relatively increased expression of CD45RB and CD45RO on synovial CD3+ T cells was seen after HDC + ASCT. No correlations were found between DAS and changes in B cells or macrophage infiltration or synoviocytes. Conclusions: HDC + ASCT results in profound but incomplete immunoablation of both the memory and naïve T cell compartment, which is associated with longlasting clinical responses in most patients. The findings provide strong circumstantial evidence for a role of T cells in established RA, and demonstrate a role for the synovium in post-transplantation T cell reconstitution.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Patientsmentioning

confidence: 99%

Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

Verburg

Flierman²,

Sont

et al. 2005

Annals of the Rheumatic Diseases

View full text Add to dashboard Cite

show abstract

“…Fifty-three patients with RA have been treated at Stanford University Medical Center since 1979 with full-dose TLI of 2,000 cGy applied to the supra-and subdiaphragmatic lymph nodes and spleen, as detailed in our previous studies (2,3,8,(10)(11)(12). All patients were administered this therapy due to lack of prior drug efficacy or because of toxic reactions to gold salts and penicillamine, but they were allowed to continue nonsteroidal antiinflammatory drugs and corticosteroids at Յ10 mg/day.…”

Section: Methodsmentioning

confidence: 99%

Treatment of rheumatoid arthritis with total lymphoid irradiation: Long-term survival

Uhrin

Wang

Matsuda

et al. 2001

Arthritis & Rheumatism

View full text Add to dashboard Cite

“…It has been suggested that in many patients with RA, the production of RF appears to be T cell independent. Thus, the production of RF has not been affected by thoracic duct drainage (28), total lymphoid irradiation (29), or anti-T cell MAb therapy (30). Since the current data indicate that BUC-ID strongly suppresses B cell function as well as RF production (7), these observations suggest the possibility that BUC may be effective in RA patients who have not responded to treatment with DP.…”

Section: Discussionmentioning

confidence: 73%

Comparative inhibitory effects of bucillamine and d‐penicillamine on the function of human b cells and t cells

Hirohata

Lipsky

1994

Arthritis & Rheumatism

View full text Add to dashboard Cite

Objective. Clinical trials have suggested that the efficacy of bucillamine (BUC) in rheumatoid arthritis (RA) may be superior to that of D-penicillamine (DP), although the basis of the ditferences remains unclear. Previous studies have revealed that BUC has unique immunomodulatory effects that depend upon its capacity to form an intramolecular disulfide (BUC-ID). We therefore examined the effects of BUC-ID on the in vitro function of human B cells and T cells compared with those of DP, at their pharmacologically attainable concentrations.Methods. IgM production was induced in highly purified B cells from healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SAC) plus interleukin-2 (IL-2) or with immobilized anti-CDSactivated CD4+ T cells. Interferon-y (IFNy) production was induced in CD4+ T cells by stimulation with immobilized anti-CD3.Results. BUC-ID suppressed IgM production induced by SAC + IL-2 as well as that induced by immobilized anti-CDSactivated CD4+ T cells, whereas DP suppressed the latter more markedly than the former. DP (3 &ml) significantly suppressed IFNy production by immobilized anti-CD3-stimulated CD4+T cells, but not IgM production induced by SAC + IL-2 stimulation. By contrast, BUC-ID (0.3 pg/ml) significantly suppressed IgM production induced by SAC + IL-2, but not T cell IFNy production. Of note, BUC-ID did not suppress IL-6 production by SAC-activated B cells.Supported by a grant from Santen Pharmaceutical Co., Ltd., Osaka, and a grant from Manabe Medical Foundation, Tokyo, Japan.Shunsei Hirohata, MD: Teikyo University School of Medicine, Tokyo, Japan; Peter E. Lipsky, MD: Harold C. Simmons Arthritis Research Center and the University of Texas Southwestem Medical Center, Dallas, Texas.Address reprint requests to Shunsei Hirohata, MD, Second Department of Internal Medicine, Teikyo University School of Medicine, 2-1 1-1 Kaga, Itabashi-ku, Tokyo 173, Japan.Submitted for publication July 30, 1993; accepted in revised form November 3, 1993. Conclusion.These results indicate that the target cells of BUC and DP in vivo might be different, with the former inhibiting the function of B cells and the latter that of T cells. The data suggest the possibility that BUC may have a different effect in RA patients compared with the effect of DP, and may be effective in patients who do not respond to DP. Bucillamine [N-(2-mercapto-2-methylpropiony1)-~-cysteine] (BUC) is a novel disease-modifying antirheumatic drug (DMARD) (1).BUC is a thiol compound that differs from D-penicillamine (DP) by the presence of 2 free sulfhydryl groups. As a result, a considerable fraction of BUC can form an intramolecular disulfide (BUC-ID) that appears to have unique immunosuppressive activities. The beneficial effects of BUC in the treatment of rheumatoid arthritis (RA) have been well appreciated in several clinical trials (1-3). Thus, BUC has come to be one of the most frequently prescribed DMARDs in Japan.It has also been shown that BUC has a beneficial effect on type I1 collagen-induced arthritis in rats (4). ...

show abstract

Dissection of the mechanisms of immune injury in rheumatoid arthritis, using total lymphoid irradiation

Cited by 31 publications

References 39 publications

Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

Outcome of intensive immunosuppression and autologous stem cell transplantation in patients with severe rheumatoid arthritis is associated with the composition of synovial T cell infiltration

Treatment of rheumatoid arthritis with total lymphoid irradiation: Long-term survival

Comparative inhibitory effects of bucillamine and d‐penicillamine on the function of human b cells and t cells

Contact Info

Product

Resources

About