Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats

Parvathi S. Kumar, Haree K. Pallera, Pamela S. Hair, Magdielis Gregory Rivera, Tushar A. Shah, Alice L. Werner, Frank A. Lattanzio, Kenji M. Cunnion, Neel K. Krishna

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model. STUDY DESIGN AND METHODS: Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry. RESULTS: Vehicle-treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury. CONCLUSIONS: These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios.

Original languageEnglish (US)
Pages (from-to)2133-2145
Number of pages13
JournalTransfusion
Volume56
Issue number8
DOIs
StatePublished - Aug 1 2016

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Complement C1
Hemolysis
Erythrocytes
Peptides
Cell Survival
Hemoglobins
Intravenous Immunoglobulins
Animal Models
Classical Complement Pathway
Erythrocyte Transfusion
Disseminated Intravascular Coagulation
Spectrophotometry
Acute Kidney Injury
Signs and Symptoms
Renal Insufficiency
Wistar Rats
Shock
Flow Cytometry
Control Groups
Antibodies

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Hematology

Cite this

Kumar, P. S., Pallera, H. K., Hair, P. S., Rivera, M. G., Shah, T. A., Werner, A. L., ... Krishna, N. K. (2016). Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats. Transfusion, 56(8), 2133-2145. https://doi.org/10.1111/trf.13674
Kumar, Parvathi S. ; Pallera, Haree K. ; Hair, Pamela S. ; Rivera, Magdielis Gregory ; Shah, Tushar A. ; Werner, Alice L. ; Lattanzio, Frank A. ; Cunnion, Kenji M. ; Krishna, Neel K. / Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats. In: Transfusion. 2016 ; Vol. 56, No. 8. pp. 2133-2145.
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Kumar, PS, Pallera, HK, Hair, PS, Rivera, MG, Shah, TA, Werner, AL, Lattanzio, FA, Cunnion, KM & Krishna, NK 2016, 'Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats', Transfusion, vol. 56, no. 8, pp. 2133-2145. https://doi.org/10.1111/trf.13674

Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats. / Kumar, Parvathi S.; Pallera, Haree K.; Hair, Pamela S.; Rivera, Magdielis Gregory; Shah, Tushar A.; Werner, Alice L.; Lattanzio, Frank A.; Cunnion, Kenji M.; Krishna, Neel K.

In: Transfusion, Vol. 56, No. 8, 01.08.2016, p. 2133-2145.

Research output: Contribution to journalArticle

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T1 - Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats

AU - Kumar, Parvathi S.

AU - Pallera, Haree K.

AU - Hair, Pamela S.

AU - Rivera, Magdielis Gregory

AU - Shah, Tushar A.

AU - Werner, Alice L.

AU - Lattanzio, Frank A.

AU - Cunnion, Kenji M.

AU - Krishna, Neel K.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - BACKGROUND: Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model. STUDY DESIGN AND METHODS: Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry. RESULTS: Vehicle-treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury. CONCLUSIONS: These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios.

AB - BACKGROUND: Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model. STUDY DESIGN AND METHODS: Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry. RESULTS: Vehicle-treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury. CONCLUSIONS: These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios.

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