Myroides Infection in a Baboon After Prolonged Pig Kidney Graft Survival

Liu, Hong; Iwase, Hayato; Wijkstrom, Martin; Singh, Jagjit; Klein, Edwin; Wagner, Robert A.; Humar, Abhinav; Pasculle, William; Cooper, David K. C.

doi:10.1097/txd.0000000000000523

Cited by 5 publications

(7 citation statements)

References 40 publications

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“…However, the baboon's circulatory state deteriorated quickly and it died as euthanasia was being considered. Blood culture was positive for Myroides spp, which has not been reported previously in any immunosuppressed patient or NHP with an organ graft [13]. Myroides spp.…”

Section: Clinical Coursesupporting

confidence: 54%

Pig kidney graft survival in a baboon for 136 days: longest life‐supporting organ graft survival to date

Iwase

Liu

Wijkstrom

et al. 2015

Xenotransplantation

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190

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The longest survival of a nonhuman primate with a life-supporting kidney graft to date has been 90 days, though graft survival >30 days has been unusual. A baboon received a kidney graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for two human complement- and three human coagulation- regulatory proteins (though only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6–1.6mg/dL) until terminally. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136 the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically-engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory agents prevented immune injury and a protein-losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality.

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Section: Clinical Coursesupporting

confidence: 54%

Pig kidney graft survival in a baboon for 136 days: longest life‐supporting organ graft survival to date

Iwase

Liu

Wijkstrom

et al. 2015

Xenotransplantation

Self Cite

190

225

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“…6 A case involving a baboon after a porcine kidney graft had a CRBSI because of this genus. 7 Among the cases published, our case is the first confirmed CRBSI in immunocompetent patients. Clinical attention should be paid to this emerging pathogen causing CRBSI.…”

Section: Discussionmentioning

confidence: 69%

<p>A Confirmed Catheter-Related Blood Stream Infection (CRBSI) in an Immunocompetent Patient Due to <em>Myroides odoratimimus</em>: Case Report and Literature Review</p>

Lu¹,

Xia²,

Zhang³

et al. 2020

IDR

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The genus Myroides are gram-negative bacilli which are completely aerobic, nonmotile, non-fermenting and yellow-pigmented with a characteristic fruity odor. Myroides species are widely found in the environment, especially in water and soil, and are considered as low-grade opportunistic pathogens for humans. Myroides infections are most commonly seen in immunocompromised patients and only rarely occur in immunocompetent patients. We here report the first confirmed catheter-related bloodstream infection (CRBSI) due to Myroides odoratimimus in an immunocompetent patient. We also review the literature related to Myroides infections.

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“…infection. 7,8 We here report life-supporting kidney transplantation in four baboons, all selected on the basis of having low anti-pig (non-Gal) antibody levels. All were administered the identical anti-CD40mAbbased regimen.…”

Section: Introductionmentioning

confidence: 99%

Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts

Iwase

Hara

Ezzelarab

et al. 2017

Xenotransplantation

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287

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Background Genetically-engineered pigs could provide a source of kidneys for clinical transplantation. The two longest kidney graft survivals reported to date have been 136 days and 310 days, but graft survival >30 days has been unusual until recently. Methods Donor pigs (n=4) were on an α1,3-galactosyltransferase gene-knockout (GTKO)/human complement-regulatory protein (CD46) background (GTKO/CD46). In addition, the pigs were transgenic for at least one human coagulation-regulatory protein. Two baboons received a kidney from a 6-gene pig (Group A) and two from a 3-gene pig (Group B). Immunosuppressive therapy was identical in all 4 cases, and consisted of anti-thymoglobulin (ATG) + anti-CD20mAb (induction) and anti-CD40mAb + rapamycin + corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R mAbs were administered to reduce the inflammatory response. Baboons were followed by clinical/laboratory monitoring of immune/coagulation/inflammatory/physiological parameters. At biopsy or euthanasia, the grafts were examined by microscopy. Results The two Group A baboons remained healthy with normal renal function >7 and >8 months, respectively, but then developed infectious complications. However, no features of a consumptive coagulopathy, e.g., thrombocytopenia, reduction of fibrinogen, or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response, and histology of biopsies taken at approximately 4, 6, and 7 months and at necropsy showed no significant abnormalities. In contrast, both Group B baboons developed features of a consumptive coagulopathy and required euthanasia on day 12. Conclusions The combination of (i) a graft from a specific 6-gene genetically-modified pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory therapy prevented immune injury, a protein-losing nephropathy, and coagulation dysfunction for >7 months. Although the number of experiments is very limited, our impression is that expression of human endothelial protein C receptor (+/− CD55) in the graft is important if coagulation dysregulation is to be avoided.

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Myroides Infection in a Baboon After Prolonged Pig Kidney Graft Survival

Cited by 5 publications

References 40 publications

Pig kidney graft survival in a baboon for 136 days: longest life‐supporting organ graft survival to date

Pig kidney graft survival in a baboon for 136 days: longest life‐supporting organ graft survival to date

<p>A Confirmed Catheter-Related Blood Stream Infection (CRBSI) in an Immunocompetent Patient Due to <em>Myroides odoratimimus</em>: Case Report and Literature Review</p>

Immunological and physiological observations in baboons with life‐supporting genetically engineered pig kidney grafts

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