Okt3 Induction via Idiotypic Networks of Mirror-Image Immunosuppressive Antiimmunoglobulins in Renal Transplant Recipients

Carreño, Marta Sitges; Yang, Wen; Esquenazi, Violet; Fuller, Laphalle; Burke, George; Milgrom, Martin L.; Roth, David B.; Ranjan, Dinesh; Miller, Jennifer

doi:10.1097/00007890-199002000-00036

Cited by 8 publications

(4 citation statements)

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“…Several interpretations are feasible. First, we have previously reported on immune modulation involving antigenic mimicry, i.e., crossreacting antiidiotypic responses between CMV and T cell membrane epitopes, the common connection being an immunosuppressed condition brought about by OKT3 in certain patients (43)(44)(45). Such a network aided by regulatory cells in the infused marrow might be operational in the DBMC group as a possible explanation for the altered CMV antibody activity.…”

Section: Discussionmentioning

confidence: 99%

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

et al. 1997

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Abstract40 recipients of first cadaver kidney transplants were given perioperative donor vertebral bone marrow infusions (DBMC), compared with 100 controls who did not receive donor bone marrow. The immunosuppressive regimen included OKT3, Tacrolimus, and steroid maintenance therapy, and, in some patients, newly introduced mycophenolate mofetil. This report describes the 24-mo actuarial follow-up and several immunological monitoring studies including sequential measurements of donor bone marrow lineage subset chimerism by the recently reported PCR-flow assay. This is a sensitive in situ PCR detection system for donor versus recipient histocompatibility genes as well as cell surface CD epitope markers using flow cytometry. The results indicate ( a ) the stabilization of the donor CD3 ϩ and CD34 ϩ cells in recipient peripheral blood at levels below 1% between 6 mo and 1 yr postoperatively, with a 10-fold higher level of donor cell chimerism of these lineages in recipient iliac crest marrow; ( b ) significantly lower levels of chimerism in peripheral blood up to 6 mo postoperatively in patients who had early acute (reversible) rejection episodes compared with those who did not; ( c ) a higher degree of chimerism seen in patients who were class II MHC HLA DR identical with their donors; ( d ) the identification of a high proportion of the donor bone marrow derived CD3 dimly staining subset of T cells (to which regulatory functions have been ascribed) in recipient peripheral blood and especially in recipient bone marrow; and ( e ) an unexpectedly increased susceptibility to clinically significant infections (primarily viral), and even death in the DBMC-infused group, compared with controls, but no graft losses because of rejection in the DBMC-infused group. Mixed lymphocyte culture assays showed a trend toward a greater number of nonspecifically low reactors in the DBMC group, as well as a greater number of nonspecifically high reactors in the controls ( P ϭ 0.058). The autologous mixed lymphocyte reaction also indicated a trend towards nonspecific immune activation in the DBMC group. Finally, anti-cytomegaloviral IgG antibody reactivity was significantly inhibited in the DBMC group 4-6 mo postoperatively ( P ϭ Ͻ 0.05). In the controls, there were no donor cell lineages detected by PCR-flow in the peripheral blood. These rather unexpected findings, indicating a more depressed cellular and humoral immune capacity in the DBMC cadaver kidney transplant recipients in this relatively early follow-up period, are discussed relevant to chimerism, MHC restriction, and suppressor activity brought about by specialized DBMC subsets, which still need to be defined. ( J. Clin. Invest. 1997. 99:1118-1129.)

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Section: Discussionmentioning

confidence: 99%

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

et al. 1997

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“…The appearance of such reactions has been correlated with improved disease prognosis after antibody therapies in other settings. [16][17][18] Four years after therapy, analysis of this long-term survivor's circulating antibodies revealed a strong anti-idiotypic HAMA response to MAT and no response against the IgG constant domains. In itself, this marks this patient as unusual in that HAMA responses were observed only in a minority of patients who were treated: ATL patients are immunosuppressed to new antigens, and typically do not make HAMAs.…”

Section: Discussionmentioning

confidence: 96%

“…and Ab3 17,18 antibodies with improved disease prognosis following immunotherapy with murine antibodies in some nonhematologic cancers. An analogous role for anti-Ab2 T cell responses in improved survival after antibody therapy has also been proposed.…”

Section: Figurementioning

confidence: 99%

Examination of a role for idiotypy in the disease remission of a long-term survivor of adult T cell leukemia treated with anti-Tac antibody

1998

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The alpha chain of the interleukin 2 receptor (IL2R␣; Tac) was targeted in clinical trials with adult T cell leukemia using murine anti-Tac antibody. Of 19 patients, a single individual achieved a durable complete remission. The mechanism of this action by murine anti-Tac has not been defined. We examined the hypothesis that the maintenance of the long-term response after treatment might be related to induction of a network of anti-idiotypic antibodies, as proposed in other tumor settings. In contrast to anti-Tac non-responders, the patient was found to have produced a human anti-mouse antibody (HAMA) response, and specifically an anti-idiotypic (

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“…Expe1imental evidence also suggests OKT3 may be a specific risk factor for CMV disease. Carrano et al (23) demonstrated that anti-anti-idiotypic antibodies, generated in some renal transplant recipients after receiving OKT3 for rejection, were specifically associated with the appearance of CMV disease. A subsequent study (24) demonstrated structural similarity between the T cell receptor /CD-3 complex and antibodies generated against CMV virion epitopes and may account in part for the association between the use of OKT3 for rescue therapy and CMV disease.…”

Section: Discussionmentioning

confidence: 99%

Prophylaxis of Cytomegalovirus in Renal Transplant Recipients

Macdonald¹,

Nicol²,

Belitsky³

et al. 1993

Canadian Journal of Infectious Diseases and Medical Microbiolog

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The incidence and outcome of cytomegalovirus (CMV) infection and disease is compared in renal transplant recipients in relation lo the use of prophylaxis wiU1 high titre anti-CMV immunoglobulin. Seventy-three CMV-negative recipients (R-) who received kidneys from CMV-posilive donors (D+) were given prophylactic CMV hyperimmune globulin inlravenously al three-week intervals lo six monilis. They also received Lhree months of oral low dose acyclovir as did the remaining 288 patients who did nol receive hyperimmune globulin. There was a low incidence of CMV disease which did not differ between groups (D+R-, 10%: D+R+, 5 .5%, D- R+, 7%: D- R-, 0.8%). The major risk factor was the use of OKT3 to treat rejection. CMV disease was seen in 22% of this group (11 of 50) . compared with only 2% (seven of 311) of those not requiring OKT3. There was only one CMV-related death. but palients with CMV disease had a reduced graft survival rate (62% versus 90%). CMV hyperimmune globulin added lo acyclovir appears to reduce the incidence of CMV disease in high risk renal recipients (D+R-) in the lower risk groups.

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Okt3 Induction via Idiotypic Networks of Mirror-Image Immunosuppressive Antiimmunoglobulins in Renal Transplant Recipients

Cited by 8 publications

References 0 publications

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

The effects of chimeric cells following donor bone marrow infusions as detected by PCR-flow assays in kidney transplant recipients.

Examination of a role for idiotypy in the disease remission of a long-term survivor of adult T cell leukemia treated with anti-Tac antibody

Prophylaxis of Cytomegalovirus in Renal Transplant Recipients

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