Antibody Titres to a Rough-Mutant Strain of Escherichia Coli in Patients Undergoing Allogeneic Bone-Marrow Transplantation

Cohen, Jonathan; Shahrukh, Hashimi,; Apperley, J.F.; Moore, Richard H.; Jones, Lydia; Aber, V. R.

doi:10.1016/s0140-6736(87)90700-8

Cited by 30 publications

(12 citation statements)

References 18 publications

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“…In particular, antibody of the M class was significantly reduced. This deficit in immunoglobulin has been reported by other groups [7], and in the case of acute leukaemia has been related to the underlying disease process [ 141. Following treatment with Pentaglobin, the levels of anti-endotoxin antibody were raised, and this was significant for IgM compared with the control group.…”

Section: Discussionsupporting

confidence: 71%

“…We have shown that children with acute leukaemias are deficient in antibody to the endotoxin core region, and that patients with the lowest concentrations of this antibody were at increased risk of developing multiple pyrexias and gram-negative infections [6]. It has also been demonstrated that patients with leukaemia undergoing BMT have reduced levels of IgG and IgM antibody to endotoxin core, and that natural IgM antibody to the core glycolipid confers protection to GvHD after allogeneic transplantation [7].…”

mentioning

confidence: 99%

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Effect of IgM‐enriched intravenous immunoglobulin (Pentaglobin) on endotoxaemia and anti‐endotoxin antibodies in bone marrow transplantation

Jackson

Parton

Barnes

et al. 1993

Eur J Clin Investigation

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Abstract. Endotoxin was measured in over 1000 plasma samples from bone marrow transplant patients in a randomized trial of the IgM-enriched intravenous immunoglobulin (IVIG) Pentaglobin. Peak endotoxaemia was significantly reduced (P=O.O2) in patients receiving Pentaglobin and 70% of all pyrexias of unknown origin were associated with endotoxaemia. Gut mucosal damage, assessed by lactulose/mannitol ratios, was significantly associated (P= 0.02) with endotoxaemia. Specific IgM antibody to endotoxin core-glycolipid was significantly raised ( P < 0.01) in patients receiving the IVIG, and the IgM fraction of Pentaglobin was found to contain most of the antiendotoxin antibody activity of the IVIG. These results suggest a role for IgM-enriched WIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant patients.

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Section: Discussionsupporting

confidence: 71%

mentioning

confidence: 99%

Effect of IgM‐enriched intravenous immunoglobulin (Pentaglobin) on endotoxaemia and anti‐endotoxin antibodies in bone marrow transplantation

Jackson

Parton

Barnes

et al. 1993

Eur J Clin Investigation

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“…on May 11, 2018. by guest www.bloodjournal.org From reduced incidence of GVHD in patients undergoing allo-bone marrow transplantation (BMT). 24 On this basis, an polyclonal antibody against the same strain of E coli was produced and was successfully used to reduce the incidence of GVHD in a randomized clinical trial. 25…”

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confidence: 99%

Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors

Penack

Holler

Brink

2010

Blood

139

114

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Acute graft-versus-host disease (GVHD) remains the major obstacle to a more favorable therapeutic outcome of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized by tissue damage in gut, liver, and skin, caused by donor T cells that are critical for antitumor and antimicrobial immunity after HSCT. One obstacle in combating GVHD used to be the lack of understanding the molecular mechanisms that are involved in the initiation phase of this syndrome. Recent research has demonstrated that interactions between microbial-associated molecules (pathogen-associated molecular patterns [PAMPs]) and innate immune receptors (pathogen recognition receptors [PRRs]), such as NOD-like receptors (NLRs) and Toll-like receptors (TLRs), control adaptive immune responses in inflammatory disorders. Polymorphisms of the genes encoding NOD2 and TLR4 are associated with a higher incidence of GVHD in HSC transplant recipients. Interestingly, NOD2 regulates GVHD through its inhibitory effect on antigen-presenting cell (APC) function. These insights identify important mechanisms regarding the induction of GVHD through the interplay of microbial molecules and innate immunity, thus opening a new area for future therapeutic approaches. This review covers current knowledge of the role of PAMPs and PRRs in the control of adaptive immune responses during inflammatory diseases, particularly GVHD.

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“…In the clinical setting, Gram-negative gut decontamination has also been shown to reduce GVHD (17,18,48), and the intensity of this decontamination has been demonstrated recently to be an important predictor of GVHD severity (19,20). Of particular interest, a study by Cohen and colleagues demonstrated that naturally occurring Ab titers to a rough-mutant strain of E. coli J5, which protect humans and animals from septic shock, were also associated with a decreased incidence of acute GVHD after allogeneic BMT (49). A follow-up study by the same group used a polyclonal antiserum against E. coli J5 as prophylaxis for acute GVHD in a prospective, double-blind, placebo-controlled trial.…”

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confidence: 99%

LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation

Cooke¹,

Gerbitz²,

Crawford³

et al. 2001

J. Clin. Invest.

268

207

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Acute graft-versus-host disease (GVHD) and leukemic relapse remain the two major obstacles to successful outcomes after allogeneic bone marrow transplantation (BMT). Recent studies have demonstrated that the loss of gastrointestinal tract integrity, and specifically the translocation of LPS into the systemic circulation, is critical to the induction of cytokine dysregulation that contributes to GVHD. Using a mouse BMT model, we studied the effects of direct LPS antagonism on GVHD severity and graft-versus-leukemia (GVL) activity. Administration of B975, a synthetic lipid-A analogue from day 0 to day +6, reduced serum TNF-α levels, decreased intestinal histopathology, and resulted in significantly improved survival and a reduction in clinical GVHD, compared with control-treated animals. Importantly, B975 had no effect on donor T cell responses to host antigens in vivo or in vitro. When mice received lethal doses of P815 tumor cells at the time of BMT, administration of B975 did not impair GVL activity and resulted in significantly improved leukemia-free survival. These findings reveal a critical role for LPS in the early inflammatory events contributing to GVHD and suggest that a new class of pharmacologic agents, LPS antagonists, may help to prevent GVHD while preserving T cell responses to host antigens and GVL activity.

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Antibody Titres to a Rough-Mutant Strain of Escherichia Coli in Patients Undergoing Allogeneic Bone-Marrow Transplantation

Cited by 30 publications

References 18 publications

Effect of IgM‐enriched intravenous immunoglobulin (Pentaglobin) on endotoxaemia and anti‐endotoxin antibodies in bone marrow transplantation

Effect of IgM‐enriched intravenous immunoglobulin (Pentaglobin) on endotoxaemia and anti‐endotoxin antibodies in bone marrow transplantation

Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors

LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation

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