Fatal Warm Autoimmune Hemolytic Anemia Resulting From IgM Autoagglutinins in an Infant With Severe Combined Immunodeficiency

Nowak‐Węgrzyn, Anna; King, Karen E.; Shirey, R. Sue; Chen, Allen; McDonough, Colleen Hope; Lederman, Howard M.

doi:10.1097/00043426-200105000-00015

Cited by 23 publications

(23 citation statements)

References 10 publications

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“…For example, autoantibody-induced agglutination in vivo almost never occurs in humans. 46 Finally, transfusion of hen egg lysozyme (HEL) Tg mRBCs into wild-type mice actively immunized to HEL surprisingly caused removal of HEL from the mRBCs, with no mRBC destruction. 47 Therefore, the current study describes novel mouse models of alloantibody-mediated intravascular and extravascular hemolysis, potentially suitable for studying HTR pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Mouse models of IgG- and IgM-mediated hemolysis

Schirmer

Song

Baliff

et al. 2006

Blood

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Well-characterized mouse models of alloimmune antibody-mediated hemolysis would provide a valuable approach for gaining greater insight into the pathophysiology of hemolytic transfusion reactions. To this end, mouse red blood cells (mRBCs) from human glycophorin A transgenic (hGPA-Tg) donor mice were transfused into non-Tg recipients that had been passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). In this novel murine "blood group system," mRBCs from hGPA-Tg IntroductionHemolytic transfusion reactions (HTRs) are dangerous complications of blood transfusions. IgM-mediated HTRs (IgM-HTRs) occur acutely, are usually due to ABO incompatibility, typically cause intravascular hemolysis, and can lead to shock, renal failure, coagulopathy, and death. 1 Although infrequent, IgM-HTRs have a high mortality rate. IgG-mediated HTRs (IgG-HTRs) are more common, but usually less severe, than IgM-HTRs; they can occur acutely or be delayed, typically cause extravascular hemolysis, and occasionally result in renal failure, coagulopathy, and death. 2 Symptomatic immune-mediated red blood cell (RBC) destruction also occurs in autoimmune hemolytic anemia (AIHA), 3 blood group incompatible transplantation, 4 and immune thrombocytopenic purpura (ITP) treated with Rh-immune globulin. 5 Although various different modalities are used to treat HTRs, there is no definitive evidence regarding efficacy. Given the sporadic nature of HTRs, designing human trials to evaluate treatment options is difficult. Therefore, to study the mechanisms underlying HTRs, to evaluate the efficacy of existing treatments, and to develop new treatments, a relevant, inexpensive, and tractable animal model is required. 6 A mouse model would be ideal for this purpose, 7 given the abundance of reagents and relevant knockout (KO) and transgenic (Tg) animals. Although mouse blood group polymorphisms exist, 8 and transfused incompatible mouse RBC (mRBCs) are rapidly cleared, 9,10 no one has exploited these findings to develop a model of HTRs. The availability of a Tg mouse expressing human glycophorin A (hGPA; gene symbol designation, GYPA) on mRBCs 11 offers an approach using a well-described glycoprotein target and well-characterized reagents.We describe initial studies validating mouse models of IgG-and IgM-mediated alloimmune hemolysis. Thus, mRBCs from hGPA-Tg donors were transfused into non-Tg recipients that were passively immunized with IgG or IgM hGPA-specific monoclonal antibodies (mAbs). The clearance of the transfused mRBCs was quantified and the roles of complement and Fc␥ receptors were evaluated. Materials and methods AntibodiesPurified mAbs NaM10-2H12 (IgG3), NaM26-3F4 (IgG1), and NaM10-6G4 (IgG2a), which recognize peptide epitopes on the M and N forms of hGPA, 12 were purchased from EFS (Nantes, France). Hybridomas producing mAb 6A7, an IgG1 specific for a sialic acid-dependent epitope on M-type hGPA, 13-15 10F7, an IgG1 recognizing a nonpolymorphic epitope on hGPA, 13,14 and J11d, a rat IgM recognizing CD24 on mRBCs, 16,17...

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Section: Discussionmentioning

confidence: 99%

Mouse models of IgG- and IgM-mediated hemolysis

Schirmer

Song

Baliff

et al. 2006

Blood

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“…The second patient developed warm IgM agglutinin autoimmune hemolytic anemia and died of this complication 40 days post-BMT. 22 The third patient with SCID received fludarabine at a dose of 1 mg/kg/day for 5 days prior to haploidentical marrow infusion. Initial engraftment was complicated by steroidrefractory Stage III GVHD of the liver and gut, but after salvage therapy with pentostatin he had no evidence of donor engraftment.…”

Section: Failure Of Engraftmentmentioning

confidence: 99%

High incidence of graft failure in children receiving CD34+ augmented elutriated allografts for nonmalignant diseases

McDonough

Jacobsohn

Vogelsang

et al. 2003

Bone Marrow Transplant

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“…It is often severe and associated with a poor prognosis in adults [3]. The prognosis of children with warm IgM autoagglutinins is unknown, but case reports from Friedmann et al [3] and Nowak-Wegrzyn et al [4] with fatal outcomes suggest that this process also carries a poor prognosis in children. Treatment of autoimmune hemolytic anemia due to IgM warm reactive autoantibodies is difficult and often incomplete with conventional immunosuppressive therapy [3].…”

Section: Introductionmentioning

confidence: 99%

Successful anti‐CD20 monoclonal antibody treatment of severe autoimmune hemolytic anemia due to warm reactive IgM autoantibody in a child with common variable immunodeficiency

et al. 2004

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Autoimmune hemolytic anemia due to warm reactive IgM autoantibodies is unusual, severe, and often fails to respond to standard immunosuppressive therapies in both adults and children. A 6-year-old girl with common variable immunodeficiency had longstanding steroid dependent, splenectomy-unresponsive, warm IgM autoantibody-mediated autoimmune hemolytic anemia. Rituximab, a monoclonal antibody directed against CD20 antigen, was used to deplete B lymphocytes and reduce autoantibody production. She received a total of six doses of rituximab (375 mg/m 2 ). Therapy was well tolerated, and B-lymphocytes were effectively depleted from the peripheral blood. The patient was completely tapered off glucocorticoids. The patient has remained off immunosuppressive agents for 16 months despite the return of B lymphocytes to the peripheral circulation. She continues to require IVIG. Early treatment with rituximab might be an option for patients with warm reactive IgM autoantibody-mediated autoimmune hemolytic anemia not responding to other treatments or experiencing untoward side effects from those treatments. Am.

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Fatal Warm Autoimmune Hemolytic Anemia Resulting From IgM Autoagglutinins in an Infant With Severe Combined Immunodeficiency

Cited by 23 publications

References 10 publications

Mouse models of IgG- and IgM-mediated hemolysis

Mouse models of IgG- and IgM-mediated hemolysis

High incidence of graft failure in children receiving CD34+ augmented elutriated allografts for nonmalignant diseases

Successful anti‐CD20 monoclonal antibody treatment of severe autoimmune hemolytic anemia due to warm reactive IgM autoantibody in a child with common variable immunodeficiency

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