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Oral Abstract

Immunohematology and Genetic Testing (red cells, leukocytes and platelets)

Oral Abstract Session - Hematology & Coagulation

#OA3-AM25-MN-21 - Use of Sutimlimab to Treat a Complement Binding Auto-anti-AnWj Antibody in a Patient with Refractory B-Cell Lymphoma

Monday, October 27, 2025
3:45 PM - 4:45 PM  PT
Room: SDCC 30AB
CE: N/A
Oral Abstracts
Background/Case Studies: Although rare, production of auto-anti-AnWj with suppression of autologous AnWj expression has been reported secondary to lymphoid malignancy. We report the use of sutimlimab, a monoclonal anti-C1s complement pathway inhibitor, and transfusion of In(Lu) red blood cells (RBC) for anemia in a patient with refractory, high-grade B cell lymphoma and auto-anti-AnWj.

Study

Design/Methods: Antibody identification was performed using commercial RBC panels, cord RBC, and AnWj-negative RBC (In(Lu) phenotype) by LISS and saline tube test (STT). Sera known to contain anti-AnWj was used for phenotyping. Adsorption was performed using papain treated autologous RBC. The plasma was treated with 0.01M dithiothreitol (DTT) to differentiate IgM and IgG. The direct antiglobulin test (DAT) was performed by tube test using monospecific anti-IgG and anti-C3 reagents. The antibody titer was determined by serial two-fold dilution of serum at 4oC and 22oC and plasma at 37oC and indirect antiglobulin test (IAT). C4d deposition was determined by flow cytometry using patient RBC resuspended in balanced salt solution incubated with C4d antibodies. In(Lu) RBC were sourced from the American Rare Donor Program. 

Results/Findings: The patient’s plasma reacted with all commercial RBC at RT, 37oC and IAT; It was non-reactive with AnWj-negative RBC, cord, and autologous RBC by LISS and STT. The DAT was positive for C3 only. Anti-AnWj sera was non-reactive with patient RBC. Four adsorptions with autologous cells removed reactivity, suggesting the anti-AnWj specificity was an autoantibody.  DTT treatment determined the antibody was both IgM and IgG isotypes. The anti-AnWj titer was 2 at 4oC and 22oC, non-reactive at 37oC and 64 at IAT. The patient received 3 AnWj-positive RBC with no change in hemoglobin but showed appropriate increment after transfusion of 3 RBC units of In(Lu) phenotype.  C4d deposition decreased by 44% on the patient’s RBC and a reduction in lactate dehydrogenase level (899 mg/dl from 1603 mg/dl) was noted 36 hours after initial sutimlimab administration. Four days after the second dose of sutimlimab, hemoglobin increased to 8.3 g/dL (nadir 4.5 g/dL), and the DAT was negative. However, the patient suffered a cardiac arrest 2 days later in the setting of progressive disease.

Conclusions: Clinically significant auto-anti-AnWj may require transfusion of AnWj-negative RBC, however, long-term transfusion may not be practical due to the rarity of In(Lu) RBC. Sutimlimab was initiated based on the complement fixing ability, identified IgM component and broad thermal reactivity of the antibody, however, the comorbid lymphoma and the short treatment period on sutimlimab limits definitive conclusions about its efficacy. Anti-complement therapy warrants further study in cases of refractory antibody-mediated hemolysis in which a role for complement is demonstrated.