Defining the clinical relevance of red blood cell autoantibodies by Monocyte Monolayer Assay

Conrado, Marina C. A. V.; D'Avila, Amanda N.; Vieira, Juliana Borges; Bonifácio, Sílvia L.; Gomes, Francisco C. A.; Dezan, Marcia Regina; Oliveira, Vítor Hugo de; Ribeiro, Ingrid Helena; Tucunduva, Luciana T. C. M.; Mendrone‐Júnior, Alfredo; Rocha, Vanderson; Dinardo, Carla Luana

doi:10.1002/jcla.22274

Cited by 8 publications

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References 7 publications

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“…The antibodies were low titer (2 and 8) and scored ≤5% in a MMA, indicating a low risk of immune mediated RBC clearance. 7,8,17,18 Samples from 127 patients (64 test and 63 controls) in the acute anemia trial were tested for antibodies to amustaline/GSH RRCs, and the majority were negative, however two control patients demonstrated S-303 antibodies 535 days and 56 days after the study began, respectively. 9 Both were inhibited by free S-300.…”

Section: Discussionmentioning

confidence: 99%

“…Although no adverse clinical outcomes or evidence of hemolysis were evident, the sponsor terminated both trials to elucidate the mechanism of this unexpected reaction. The antibodies were low titer (2 and 8) and scored ≤5% in a MMA, indicating a low risk of immune mediated RBC clearance 7,8,17,18 . Samples from 127 patients (64 test and 63 controls) in the acute anemia trial were tested for antibodies to amustaline/GSH RRCs, and the majority were negative, however two control patients demonstrated S‐303 antibodies 535 days and 56 days after the study began, respectively 9 .…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells

et al. 2020

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Background: The INTERCEPT™ Blood System for Red Blood Cells (RBCs) utilizes amustaline (S-303) and glutathione (GSH) to inactivate pathogens and leukocytes in transfused RBCs. Treatment-emergent low titer non-hemolytic antibodies to amustaline/GSH RBC were detected in clinical trials using a prior version of the process. The amustaline/GSH process was re-formulated to decrease S-303 RBC adduct formation. Study Design and Methods: A standard three-cell antibody screening panel was modified to include reagent red cells (RRC) with high (S-303H) or low (S-303L) S-303 adduct density as assessed by flow cytometry, representative of the original and current amustaline/GSH treatment processes, respectively. General hospital and RBC transfusion-dependent patients never exposed, and clinical trial subjects exposed to amustaline/GSH RBC were screened for antibodies to amustaline/GSH RBC using a standardized agglutination assay. Results: Twelve (0.1%) of 10,721 general hospital and 5 (0.5%) of 998 repeatedly-transfused patients not previously exposed to amustaline/GSH RBCs expressed natural, low titer (2-32) IgM and/or IgG (non-IgG 1 or IgG 3 isotype) antibodies with acridine (a structural element of amustaline) (n = 14) or nonacridine (n = 3) specificity. 11 of 17 sera reacted with S-303L panel RRCs. In clinical studies 81 thalassemia and 25 cardiac surgery patients were transfused with a total of 1085 amustaline/GSH RBCs and no natural or treatmentemergent S-303 antibodies were detected. Conclusion: Standardized RRC screening panels are sensitive for the detection of natural and acquired S-303-specific antibodies. Natural low titer antibodies to amustaline/GSH RBC are present in 0.15% of naïve patients. The clinical relevance of these antibodies appears minimal but is under further investigation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells

et al. 2020

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“…The MMA comprised three steps: buffy coat purification, RBC adsorption with AUS and quantification of in vitro phagocytosis .…”

Section: Methodsmentioning

confidence: 99%

Prevalence and laboratorial determinants of the clinical relevance of antibodies of undetermined specificity

et al. 2019

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Background and Objectives Antibodies of unknown specificity (AUS) are frequently identified in the pre‐transfusion testing. These antibodies can be insignificant or potentially cause post‐transfusion haemolysis. Information about the prevalence of clinically relevant AUS is still lacking. Our aim was to predict the potential clinical relevance of AUS using the monocyte monolayer assay (MMA) and to identify the clinical and laboratorial determinants of AUS’ significance. Materials and Methods Antibodies of unknown specificity identified at a single institution from 2015–2017 were evaluated through MMA. A monocyte index (MI) of more than 5% was predictive of potential post‐transfusion haemolysis. Results Thirty‐two patients with AUS were included in the study. Of the studied AUS, 37·5% (12/32) presented with a monocyte index (MI) more than 5%. In the group of significant AUS, 41·7% of the patients presented with sickle cell disease (SCD) and the AUS were associated with Rh antibodies in 75% of the cases. In the group of insignificant AUS, only 10% of the patients had SCD and the association with Rh antibodies was detected in 20% of the cases. The presence of Rh antibodies was independently associated with the AUS clinical relevance (P = 0·012). Conclusion More than one‐third of the AUS are potentially clinically relevant, and the association with Rh antibodies is predictive of AUS relevance. Services must honour AUS in the pre‐transfusion process in order to ensure transfusion safety.

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“…This modified MMA has been previously described in the literature by our team, [6][7][8] demonstrating accuracy in the evaluation of the clinical relevance of both auto-and alloantibodies.…”

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Accelerated erythrocyte destruction mimicking post‐transfusion hyperhaemolysis in the course of uncomplicated vaso‐occlusive crisis associated with sickle cell disease

Conrado

Fonseca

Dezan

et al. 2020

Transfusion Medicine

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This report regards a 40-year-old man, diagnosed with sickle cell anaemia (SCA; HbSS), who was admitted to our emergency service with symptoms of vaso-occlusive crisis. The patient was not under chronic transfusion therapy, and the baseline haemoglobin was 7 g/dL. He was initially treated with opioid analgesics and hydration. The initial laboratory investigation showed Hb = 7.1 g/dL, Ht = 21.1%, lactate dehydrogenase (LDH) = 384 U/L, total bilirubin = 2.3 mg/dL and indirect bilirubin = 1.32 mg/dL. Anti-E and anti-Di a were identified in the antibody screening using the gel method (ID-DiaPanel and ID-DiaPanel-P, BIORAD, Lagoa Santa, Brazil). Previous immunohaematological investigation had shown only anti-E. He was transfused with two red blood cell (RBC) units (254 and 261 mL), without any clinical intercurrences during the infusion. The patient's phenotype was R 0 r; K−; Jk(a + b−); Fy(a + b−); S−, s+ and Dia−, and the transfused units had the same phenotype. In addition, molecular investigation for the most common RHD 1 and RHCE variants (Restriction Fragment Length Polymorphism-RFLP-PCR designed to detect c.733C>G) was performed and was negative. All transfused units were HbS-negative, and the patient's blood volume was 4.5 L. The laboratory tests performed approximately 8 hours after the transfusion revealed a sharp decrease in the haemoglobin levels (posttransfusion Hb = 5 g/dL) and an increase in LDH (550 U/L). Parvovirus polymerase chain reaction was performed and was negative.

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Defining the clinical relevance of red blood cell autoantibodies by Monocyte Monolayer Assay

Abstract: MMA can be used to evaluate the ability of RBC autoantibodies to mediate overt hemolysis. It can be especially useful to determine the role played by cold and warm auto-antibodies in mixed auto-immune hemolytic disease, helping to define the best treatment option.

Cited by 8 publications

References 7 publications

Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells

Prevalence of natural and acquired antibodies to amustaline/glutathione pathogen reduced red blood cells

Prevalence and laboratorial determinants of the clinical relevance of antibodies of undetermined specificity

Accelerated erythrocyte destruction mimicking post‐transfusion hyperhaemolysis in the course of uncomplicated vaso‐occlusive crisis associated with sickle cell disease

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