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Complement activating ABO anti-A IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible transfusions.

ABSTRACT: BACKGROUND:Typically minor ABO incompatible platelet products are transfused without any incident, yet serious hemolytic transfusion reactions occur. To mitigate these events, ABO 'low titer' products are used for minor ABO incompatible transfusions. We sought to understand the role of IgM/IgG and complement activation by anti-A on extravascular hemolysis. METHODS:Samples evaluated included (i) Group O plasma from a blood donor whose apheresis platelet product resulted in an extravascular transfusion reaction, (ii) Group O plasma from 12 healthy donors with matching titers that activated complement (N?=?6) or not (N?=?6), and (iii) Group O sera from 10 patients with anti-A hemolysin activity. A flow cytometric monocyte erythrophagocytosis assay was developed using monocytes isolated by immunomagnetic CD14-positive selection from ACD whole blood of healthy donors. Monocytes were frozen at -?80 °C in 10% dimethyl sulfoxide/FBS and then thawed/reconstituted on the day of use. Monocytes were co-incubated with anti-A-sensitized fluorescently-labeled Group A1?+?RBCs with and without fresh Group A serum as a source of complement C3, and erythrophagocytosis was analyzed by flow cytometry. The dependency of IgM/IgG anti-A and complement C3 activation for RBC erythrophagocytosis was studied. Anti-A IgG subclass specificities were examined for specific samples. RESULTS:The plasma and sera had variable direct agglutinating (IgM) and indirect (IgG) titers. None of 12 selected samples showed monocyte-dependent erythrophagocytosis with or without complement activation. The donor sample causing a hemolytic transfusion reaction and 2 of the 10 patient sera with hemolysin activity showed significant erythrophagocytosis (>?10%) only when complement C3 was activated. The single donor plasma and two sera demonstrating significant erythrophagocytosis had high IgM (??128) and IgG titers (>?1024). The donor plasma anti-A was IgG1, while the patient sera were an IgG3 and an IgG1 plus IgG2. CONCLUSION:High anti-A IgM/IgG titers act synergistically to cause significant monocyte erythrophagocytosis by activating complement C3, thus engaging both Fc?- and CR1-receptors.

SUBMITTER: Pandey P

PROVIDER: S-EPMC7257204 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Complement activating ABO anti-A IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible transfusions.

Pandey Priyanka P Anani Waseem Q WQ Pugh Tina T Gottschall Jerome L JL Denomme Gregory A GA

Journal of translational medicine 20200528 1

<h4>Background</h4>Typically minor ABO incompatible platelet products are transfused without any incident, yet serious hemolytic transfusion reactions occur. To mitigate these events, ABO 'low titer' products are used for minor ABO incompatible transfusions. We sought to understand the role of IgM/IgG and complement activation by anti-A on extravascular hemolysis.<h4>Methods</h4>Samples evaluated included (i) Group O plasma from a blood donor whose apheresis platelet product resulted in an extra ...[more]

PMID: 32466782

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Project description:Background and objectivesABO blood group-incompatible kidney transplantation is considered a safe procedure, with noninferior outcomes in large cohort studies. Its contribution to living kidney transplantation programs is substantial and growing. Outcomes compared with center-matched ABO blood group-compatible control patients have not been ascertained.Design, setting, participants, & measurementsComprehensive searches were conducted in Embase, Medline, Cochrane, Web-of-Science, and Google Scholar. Meta-analyses Of Observational Studies in Epidemiology study guidelines for observational studies and Newcastle Ottawa bias scale were implemented to assess studies. Meta-analysis was performed using Review Manager 5.3. A subgroup analysis on antibody removal technique was performed.ResultsAfter identifying 2728 studies addressing ABO-incompatible kidney transplantation, 26 studies were included, describing 1346 unique patients who were ABO-incompatible and 4943 ABO-compatible controls. Risk of bias was low (all studies ?7 of 9 stars). Baseline patient characteristics revealed no significant differences in immunologic risk parameters. Statistical heterogeneity of studies was low (I2 0% for graft and patient survival). One-year uncensored graft survival of patients who were ABO-incompatible was 96% versus 98% in ABO-compatible controls (relative risk, 0.97; 95% confidence interval, 0.96 to 0.98; P<0.001). Forty-nine percent of reported causes of death in patients who were ABO-incompatible were of infectious origin, versus only 13% in patients who were ABO-compatible (P=0.02). Antibody-mediated rejection (3.86; 95% confidence interval, 2.05 to 7.29; P<0.001), severe nonviral infection (1.44; 95% confidence interval, 1.13 to 1.82; P=0.003), and bleeding (1.92; 95% confidence interval, 1.36 to 2.72; P<0.001) were also more common after ABO-incompatible transplantation.ConclusionsABO-incompatible kidney transplant recipients have good outcomes, albeit inferior to center-matched ABO-compatible control patients.

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Complement activating ABO anti-A IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible transfusions.

Publications

Complement activating ABO anti-A IgM/IgG act synergistically to cause erythrophagocytosis: implications among minor ABO incompatible transfusions.

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