How I manage cold agglutinin disease

Berentsen, Sigbjørn

doi:10.1111/j.1365-2141.2011.08643.x

Cited by 78 publications

(87 citation statements)

References 68 publications

(112 reference statements)

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“…29 In contrast, monoclonal cold agglutinins with high thermal amplitude are characteristic for CAD. 30 CAD is characterized by IgM-mediated agglutination of RBCs in the microcirculation exposed to lower temperatures, e.g. fingers, toes, etc., which becomes clinically apparent as acrocyanosis.…”

Section: Complement-mediated Hemolysis In Igm-mediated Aihamentioning

confidence: 99%

“…31 Depending on the strength of the cold agglutinin titer (which goes in parallel with the density of cold-agglutinin deposition on RBCs) and the width of the thermal amplitude cold-agglutinins can also induce complement activation. 30,32 This is illustrated by the fact that C3 deposition on RBC membranes increases and C1s levels in plasma decrease with increasing titers of cold agglutinins. …”

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confidence: 99%

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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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Section: Complement-mediated Hemolysis In Igm-mediated Aihamentioning

confidence: 99%

mentioning

confidence: 99%

Complement inhibitors to treat IgM-mediated autoimmune hemolysis

Wouters

2015

Haematologica

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“…Autoimmune hemolytic anemias can be classified depending on presence of warm, cold or mixed type of autoantibodies that are directed against antigens on the red blood cell (RBC) surface [1]. The autoantibodies may be idiopathic (primary) or secondary to conditions such as infection, malignancy, or immune disease [2].…”

Section: Introductionmentioning

confidence: 99%

Resolution of Serologic Problems Due to Cold Agglutinins in Chronic Lymphocytic Leukemia

Javed

Datta

Basu

et al. 2016

Indian J Hematol Blood Transfus

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“…cyclophosphamide or chlorambucil) are used but limited by myelotoxicity. 23,26 Most patients who respond to immunosuppressive agents have underlying B-cell neoplasms.…”

Section: Case Presentationmentioning

confidence: 99%

“…Rituximab has been studied as a single agent as well as in combination with steroids, oral Fludarabine (not available in the United States), and interferon (Table 2). 20,23,24,25 Immunosuppressive agents (e.g. cyclophosphamide or chlorambucil) are used but limited by myelotoxicity.…”

Section: Case Presentationmentioning

confidence: 99%