Immune modulation by ionized irradiation

Tochner, Zelig; Slavin, Shimon

doi:10.1016/0952-7915(88)90012-x

Cited by 8 publications

(4 citation statements)

References 23 publications

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“…Irradiation of lymphoid tissue will interfere with the allogeneic response to the graft and in theory will provide additional immunosuppression to that achieved using conventional drug-based immunosuppression (2,3). The success of lymphoid irradiation in cardiac and renal allograft rejection has previously been demonstrated (4,5).…”

Section: Introductionmentioning

confidence: 99%

The Safety and Efficacy of Total Lymphoid Irradiation in Progressive Bronchiolitis Obliterans Syndrome After Lung Transplantation

Fisher

Rutherford

Bozzino

et al. 2005

American Journal of Transplantation

108

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Total lymphoid irradiation (TLI) has been used to control renal and cardiac allograft rejection. Data evaluating TLI in bronchiolitis obliterans syndrome (BOS), the physiological manifestation of chronic lung allograft rejection, is very limited. We present our single center experience of the safety and efficacy of TLI in controlling progressive BOS in a retrospective study.Over 12 years, 37 lung recipients (16 M:21 F) who had undergone 13 single; 12 bilateral and 12 heart-lung transplants were treated with TLI for progressive BOS. Grades at time TLI given were BOS 1 (n = 7) BOS 2 (n = 14) BOS 3 (n = 16). Twenty-seven (73%) completed >8/10 fractions, 10 (27%) failed to complete TLI. Two died from advanced BOS during treatment, 8 stopped early (range 3-7 fractions) due to marrow suppression (6) or infection (2). In the 27 recipients who completed >8/10 fractions, decline in FEV1 was 122.7 mls/month pre-TLI and 25.1 mls/month post-TLI, p = 0.0004, mean (95% CI) change in rate of decline was 97.5 (48.2-146.7) mls/month. TLI significantly reduces the rate of decline in graft function associated with BOS. TLI is well tolerated and associated with few serious complications and is an appropriate immunosuppressive approach in progressive BOS.

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Section: Introductionmentioning

confidence: 99%

The Safety and Efficacy of Total Lymphoid Irradiation in Progressive Bronchiolitis Obliterans Syndrome After Lung Transplantation

Fisher

Rutherford

Bozzino

et al. 2005

American Journal of Transplantation

108

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“…Ionized radiation has a combined immunosuppressive and immunomodulatory effect by depleting cytotoxic lymphocytes and increasing and enhancing regulatory T lymphocytes. [18][19][20] In CLAD, TLI may stop the inflammatory cascade and subsequent dysfunctional wound healing process, resulting in further fibrosis. Fucks et al…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of total lymphoid irradiation in different chronic lung allograft dysfunction phenotypes

Geng-Cahuayme

Sáez-Giménez

Altabas-González

et al. 2023

Clinical Transplantation

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Total lymphoid irradiation (TLI) is an alternative treatment for chronic lung allograft dysfunction (CLAD). However, data regarding its efficacy and tolerance are scarce. This study included patients with CLAD treated with TLI at our center between 2011 and 2018. Clinical characteristics before and after TLI and related complications were analyzed. Forty patients with CLAD (twenty‐nine bronchiolitis obliterans syndrome [BOS], nine restrictive allograft syndrome [RAS], and two mixed) were included. Significant attenuation of the forced expiratory volume in 1‐sec (FEV1) decline slope was observed in all phenotypes, in both the BOS and RAS. The median FEV1 12, 6, and 3 months pre‐TLI were as follows: 1980 (IQR 1720‐2560), 1665 (IQR 1300‐2340) and 1300 (IQR 1040‐1740) ml (p < .001), while the median FEV1 at 3, 6, and 12 months post‐TLI was 1110 (IQR 810–1440), 1130 (IQR 860–1470), and 1115 (IQR 865–1490) ml (p = .769). No dropouts due to radiation toxicity were observed. The mean survival according to the Karnofsky Performance Status Scale (KPS) >70 or ≤70 at baseline was 1837 (IQR 259–2522) versus 298 (IQR 128–554) days (p < .0001), respectively. In conclusion, TLI may stop FEV1 decline in both BOS and RAS. Moreover, a good KPS score may be an important prognostic factor.

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“…Previous studies on mice treated with ionizing irradiation, involving either TBI (12], or TLI [26,27]. showed that irradiation markedly suppresses T cell-dependent immune function by inducing selective T cell lymphopenia [28]. Henee, it is not surprising that significant prolongation of survival, accompanied by amelioration of all disease parameters, was reported in MRL/lpr mice treated with high-dose CY or lethal TBI.…”

Section: Effect Of Sbmt On Histological Manifestations Of Renal Diseasementioning

confidence: 99%

Immunomodulation of autoimmunity in MRL/lpr mice with syngeneic bone marrow transplantation (SBMT)

Karussis

Vourka-Karussis

Lehmann

et al. 1995

Clinical and Experimental Immunology

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SUMMARYMRL-lpr/Ipr mice spontaneously develop a severe autoimmune syndrome, characterized by massive generall/ed lymphadenopathy. arthritis, arteritis, dermatitis and immune complexmediated glomerulonephritis. Bone marrow transplantation (BMT) from MHC-matched systemic lupus erythematosus (SLE)-resistant donors to susceptible recipients has proved effective in correcting autoimmune manifestations in autoimmune-prone mice. We investigated the effect of syngeneif BMT from MRL/lpr (donor) to immunocompromised MRL/lpr (recipient), after purging the bone marrow inoculum with MoAbs against mature T cells (anti-Thy 1.2). All the untreated mice developed lymphadenopathy and by iheageof 36 weeks five of the eight were dead; in contrast, all the mice which underwent syngeneic BMT following acute immunosuppression with total body irradiation (900 cGy) (TBI) remained disease-free. In an additional experiment, it was found that conditioning with cyclophosphamide (CY) before BMT was more effective than TBI in inhibiting delayed-onset autoimmune manifestations (mean survival 350 days in the CY group and 305 days in the TBI group, vcr.su.s 197 days in untreated controls). Under both immunosuppressive regimens T cell-depleted bone marrow grafts produced far better results than did unmanipulated BMT. Following syngeneic BMT the incidence of proteinuria and the level of serum anti-DNA (dd) antibodies were significantly reduced, compared with that of the agematched untreated controls. CY was more effective than TBI in reducing the anti-DNA titres. Likewise. T depletion of bone marrow inocula before BMT induced a more drastic drop in autoantibodies, following both CY and TBI conditioning protocols. After syngeneic BMT (either CY or TBI) no signs of lymphadenopathy were observed even at an advanced age. Upon histopathological examination, the BMT-treated mice displayed normal glomeruli with occasional minimal signs of glomerulonephritis. Syngeneic T cell-depleted BMT following acute cytoreduction of anti-self immune lymphocytes may represent a new therapeutic approach for drug-resistant autoimmune diseases.

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Immune modulation by ionized irradiation

Cited by 8 publications

References 23 publications

The Safety and Efficacy of Total Lymphoid Irradiation in Progressive Bronchiolitis Obliterans Syndrome After Lung Transplantation

The Safety and Efficacy of Total Lymphoid Irradiation in Progressive Bronchiolitis Obliterans Syndrome After Lung Transplantation

Efficacy and safety of total lymphoid irradiation in different chronic lung allograft dysfunction phenotypes

Immunomodulation of autoimmunity in MRL/lpr mice with syngeneic bone marrow transplantation (SBMT)

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