Hemolytic anemia due to warm autoantibodies

Packman, Charles H.

doi:10.1016/j.blre.2007.08.001

Cited by 145 publications

(159 citation statements)

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“…AIHA can affect both children (mainly before the age of 5) and adults, with an estimated annual incidence of 1 to 3 per 100,000 individuals [1,2]. The classification of AIHA is mainly based on the immunochemical properties of the red blood cell autoantibody [3,4]. Warm antibody AIHA (wAIHA) accounts for approximately 75-80% of all adult AIHA cases [1,3].…”

Section: Introductionmentioning

confidence: 99%

Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients

et al. 2014

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Warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease with poorly known natural history and management remaining mainly empirical. To better describe the characteristics and outcome of wAIHA in adults, we performed a single-center cohort study of patients diagnosed with wAIIHA from 2001 to 2012 in our center. Sixty patients (50% women) were included, the mean age at the time of wAIHA onset was 54 6 23 years. wAIHA was considered "primary" for 21 patients (35%) and was associated with an underlying disorder in 39 (65%), including mainly lymphoproliferative disorders and systemic lupus. All patients but two needed treatment and received corticosteroids, with an overall initial response rate of 87%. However, 63% of the patients were corticosteroid-dependent and 56% required at least one second-line treatment including mainly rituximab (n 5 19). At the time of analysis, after a mean follow-up of 46 months, 28 patients (47%) were in remission and off treatment and 5 (8%) had died. The presence of an underlying lymphoproliferative disorder was associated with reduced response to corticosteroids and increased need for second-line therapy. In conclusion, in the last decade and compared to a previous series from our center, the rate of secondary wAIHA has increased and the use of rituximab has emerged as the preferred second-line treatment and corticosteroid-sparing strategy; the overall mortality has significantly decreased (8 vs. 18%).Am. J. Hematol. 89:E150-E155,

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Section: Introductionmentioning

confidence: 99%

Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients

et al. 2014

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“…[1][2][3] Based on the optimal binding temperature, AIHA is classified into warm autoantibody AIHA (WA-AIHA), cold autoantibody AIHA (CA-AIHA), and mixed forms, respectively. [1][2][3] The diagnosis of AIHA is based on the presence of hemolytic anemia with a positive direct antiglobulin test (DAT) for IgG and/or complement C3d. The degree of anemia at presentation correlates with the severity of AIHA and with the probability of relapse.…”

Section: Introductionmentioning

confidence: 99%

Complement inhibitors to treat IgM-mediated autoimmune hemolysis

Wouters

2015

Haematologica

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© F e r r a t a S t o r t i F o u n d a t i o n Complement systemThe complement system is an evolutionary highly conserved cascade system that makes up part of the innate immune system. [7][8][9] Complement activation can occur via three distinct pathways (classical pathway (CP), lectin pathway (LP) and alternative pathway (AP) that converge at the level of C3 cleavage and eventually lead to a common terminal pathway (TP) ( Figure 1A).The AP can be initiated by spontaneous hydrolysis of the central complement component into C3b(H 2 O). C3b(H 2 O) is an acceptor for the next AP protein Factor B (FB) which is then cleaved by the serine protease factor D (FD), resulting Complement inhibition in AIHA haematologica | 2015; 100 (11) 1389 The lectin pathway is initiated by binding of MBL (or ficolins) to sugar structures followed by activation of C2 and C4 by MASP1/MASP2, leading to the formation of lectin C3 convertase (C2aC4b). (E) C3-activation by the classical, lectin or alternative C3 convertase results in the formation of the C5 convertase. C5 convertase subsequently activates C5 resulting in the formation of the membrane attack complex (MAC). C: complement factor; MAC: membrane attack complex; MBL: mannan binding lectin; MASP: MBL-associated serine protease; P: properdin; C1-inh: C1-inhibitor; FI: factor I; CR1: complement receptor 1; MCP: membrane co-factor protein; DAF: decay accelerating factor; C4BP: C4-binding protein; FH: factor H. A B C D E © F e r r a t a S t o r t i F o u n d a t i o nin the fluid phase C3 convertase (C3b(H 2 O)Bb), that can cleave multiple C3 molecules into C3b and C3a. C3b binds to nucleophilic targets on cell membranes 10 and C3a acts as a pro-inflammatory anaphylatoxin ( Figure 1B). Low-level activation of C3 can significantly be accelerated through a positive feedback loop resulting in the formation of additional alternative C3 convertases on the surface (C3bBb) that are stabilized by properdin (P) and eventually give rise to the formation of a C5 convertase (C3bBbC3b), which subsequently cleaves C5 into C5b and C5a.10 C5b attaches to the surface and subsequently binds to C6, C7 and C8 to form the C5bC8 complex allowing polymerization of C9 to form the membrane attack complex (MAC), which inserts into target membranes and induces cell lysis ( Figure 1A and E). 11,12 Next to lysis by the MAC, cleavage of both C3 and C5 results in the generation of pro-inflammatory anaphylatoxins (C3a, C5a) that attract and activate leukocytes 13 and C3b opsonization of the target surface facilitates uptake by phagocytic cells in the liver and spleen.During evolution complement activation became more specific by the development of recognition molecules. The CP is initiated by binding of C1q to the Fc-part of IgM or IgG complexed with their target antigens. IgM is most efficient in complement activation, due to its polymeric nature. Human IgG activates complement in the order IgG3>IgG1>IgG2, whereas IgG4 does not activate complement at all.14 As the affinity of C1q for a single IgG Fc tail is...

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“…D antigen is the most immunogenic antigen in the setting of the development of alloantibodies following exposure; however, it is not commonly associated with autoantibody development. Antibodies against antigens in the Rh system, such as anti-e, anti-E, and anti-c, are more commonly implicated in warm AIHA [22][23][24]. The presence of only anti-D antibodies is rare in AIHA, and autoanti-D antibodies have been detected in only a few cases, such as in the setting of myelodysplasia, Burkitt's lymphoma, and a paraneoplastic syndrome associated with breast cancer [25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Relationship between Autoimmune Diseases and Imbalances in Helper/Suppressor T-cell Populations after Rituximab-containing Chemotherapyfor Non-Hodgkin Lymphoma

Oka¹,

Hiramatsu²,

Kawano³

et al. 2017

J Cancer Sci Ther

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Immunologic abnormalities including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) have been described in patients with non-Hodgkin lymphoma. In some cases, anti-red cell or platelet antibodies are produced by lymphoma cells. However, cases of the occurrence of autoimmune diseases without recurrence of lymphomas have been also reported. The relationship between autoimmune diseases with post-bone marrow transplantation and Hodgkin disease may be attributed to immune dysfunctions, particularly those involving T cells. This autoimmune phenomenon may be related to imbalances in helper/suppressor T-cell populations. Imbalances in helper and suppressor T-cell populations have been reported after R-CHOP chemotherapy, and the recovery of serum IgG and CD4+ counts was observed more than 2 years after R-CHOP therapy in patients with B-cell lymphoma. In this report, we present a case of an 87-year-old man who was treated with rituximab-containing chemotherapy and maintained complete remission. However, the immunophenotyping of peripheral blood and bone mallow mononuclear cells revealed a reversed CD4/CD8 ratio. Two years later, he developed ITP. He was treated with intravenous immunoglobulin and eltrobopag, and thrombocytopenia improved. Five years later, he developed pneumonia and sudden Coombs-positive hemolytic anemia caused by autoantibodies against D antigen and thrombocytopenia without the recurrence of lymphoma. He was treated with prednisolone and a pulse dose of methylprednisolone; however, his response to therapy was poor and he subsequently died. We herein report a case who have been showed reversed imbalances in the helper/suppressor T cell populations over 2 years after R-CHOP therapy, developed AIHA and ITP without recurrence of lymphoma. The long-term monitoring of T-cell counts after rituximab containing chemotherapies is important, and careful attention to infection signs.

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Hemolytic anemia due to warm autoantibodies

Cited by 145 publications

References 103 publications

Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients

Characteristics and outcome of warm autoimmune hemolytic anemia in adults: New insights based on a single‐center experience with 60 patients

Complement inhibitors to treat IgM-mediated autoimmune hemolysis

Relationship between Autoimmune Diseases and Imbalances in Helper/Suppressor T-cell Populations after Rituximab-containing Chemotherapyfor Non-Hodgkin Lymphoma

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