Complement and Complement Components in Acquired Hemolytic Anemia with High Titer Cold Antibodies

Jonsen, Jon; Kåss, Erik; Harboe, Morten

doi:10.1111/j.0954-6820.1961.tb00291.x

Cited by 18 publications

(9 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Antigen-bound IgM is a potent complement activator (82)(83)(84). Following cold-induced binding of CA to the RBCs during passage through the acral parts of the circulation, the AgAb complex induces fixation of complement protein C1q and, thereby, complement activation by the classical pathway (Figure 3) (84)(85)(86)(87)(88). C1 esterase activates C4 and C2, thus generating C3 convertase which results in the formation of C3a, a soluble anaphylotoxin, and C3b, an opsonin with enzymatic activity (84,89).…”

Section: Complement Activation and Hemolysismentioning

confidence: 99%

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

2020

View full text Add to dashboard Cite

Autoimmune hemolytic anemias mediated by cold agglutinins can be divided into cold agglutinin disease (CAD), which is a well-defined clinicopathologic entity and a clonal lymphoproliferative disorder, and secondary cold agglutinin syndrome (CAS), in which a similar picture of cold-hemolytic anemia occurs secondary to another distinct clinical disease. Thus, the pathogenesis in CAD is quite different from that of polyclonal autoimmune diseases such as warm-antibody AIHA. In both CAD and CAS, hemolysis is mediated by the classical complement pathway and therefore can result in generation of anaphylotoxins, such as complement split product 3a (C3a) and, to some extent, C5a. On the other hand, infection and inflammation can act as triggers and drivers of hemolysis, exemplified by exacerbation of CAD in situations with acute phase reaction and the role of specific infections (particularly Mycoplasma pneumoniae and Epstein-Barr virus) as causes of CAS. In this review, the putative mechanisms behind these phenomena will be explained along with other recent achievements in the understanding of pathogenesis in these disorders. Therapeutic approaches have been directed against the clonal lymphoproliferation in CAD or the underlying disease in CAS. Currently, novel targeted treatments, in particular complement-directed therapies, are also being rapidly developed and will be reviewed.

show abstract

Section: Complement Activation and Hemolysismentioning

confidence: 99%

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

2020

View full text Add to dashboard Cite

show abstract

“…CA binds to its antigen at the erythrocyte surface during passage through the cooler parts of the peripheral circulation, causing agglutination of red blood cells and complement activation by the classical pathway. 12,16,17,45,46 IgM is a potent classical pathway trigger, and the antigen-IgM complex binds complement protein C1q. C1 esterase then activates C2 and C4, generating C3 con-vertase which cleaves C3 into C3a and C3b.…”

Section: A Complement-mediated Immune Hemolytic Anemiamentioning

confidence: 99%

“…3,[12][13][14][15] Complement activation via the classical pathway is essential for subsequent hemolysis. [16][17][18][19][20][21] Recent advances in CAD include the demonstration of a distinct clonal B-cell LPD, the documentation of effective B-cell-directed therapies, and the development of novel complement-directed therapies. This review will focus on these achievements, which also raise some challenges.…”

Section: Introductionmentioning

confidence: 99%

<p>Cold agglutinin disease: current challenges and future prospects</p>

Berentsen¹,

Roth²,

Randen³

et al. 2019

JBM

View full text Add to dashboard Cite

Cold agglutinin disease (CAD) is a complement-dependent, classical pathway-mediated immune hemolytic disease, accounting for 15–25% of autoimmune hemolytic anemia, and at the same time, a distinct clonal B-cell lymphoproliferative disorder of the bone marrow. The disease burden is often high, but not all patients require pharmacological treatment. Several therapies directed at the pathogenic B-cells are now available. Rituximab plus bendamustine or rituximab monotherapy should be considered first-line treatment, depending on individual patient characteristics. Novel treatment options that target the classical complement pathway are under development and appear very promising, and the C1s inhibitor sutimlimab is currently being investigated in two clinical Phase II and III trials. These achievements have raised new challenges and further prospects, which are discussed. Patients with CAD requiring therapy should be considered for clinical trials.

show abstract

“…Cooling of blood during passage through acral parts of the circulation allows CA to bind to RBC and cause agglutination ( Figure 3 ). Being a strong complement activator, antigen-bound IgM-CA on the cell surface binds C1 and thereby initiates the classical complement pathway [ 8 , 56 , 57 ]. C1 esterase activates C4 and C2, generating C3 convertase, which results in the cleavage of C3 to C3a and C3b.…”

Section: Primary Chronic Cold Agglutinin Diseasementioning

confidence: 99%

Red Blood Cell Destruction in Autoimmune Hemolytic Anemia: Role of Complement and Potential New Targets for Therapy

Berentsen

Sundic

2015

BioMed Research International

View full text Add to dashboard Cite

Autoimmune hemolytic anemia (AIHA) is a collective term for several diseases characterized by autoantibody-initiated destruction of red blood cells (RBCs). Exact subclassification is essential. We provide a review of the respective types of AIHA with emphasis on mechanisms of RBC destruction, focusing in particular on complement involvement. Complement activation plays a definitive but limited role in warm-antibody AIHA (w-AIHA), whereas primary cold agglutinin disease (CAD), secondary cold agglutinin syndrome (CAS), and paroxysmal cold hemoglobinuria (PCH) are entirely complement-dependent disorders. The details of complement involvement differ among these subtypes. The theoretical background for therapeutic complement inhibition in selected patients is very strong in CAD, CAS, and PCH but more limited in w-AIHA. The optimal target complement component for inhibition is assumed to be important and highly dependent on the type of AIHA. Complement modulation is currently not an evidence-based therapy modality in any AIHA, but a number of experimental and preclinical studies are in progress and a few clinical observations have been reported. Clinical studies of new complement inhibitors are probably not far ahead.

show abstract

Complement and Complement Components in Acquired Hemolytic Anemia with High Titer Cold Antibodies

Cited by 18 publications

References 12 publications

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia

<p>Cold agglutinin disease: current challenges and future prospects</p>

Red Blood Cell Destruction in Autoimmune Hemolytic Anemia: Role of Complement and Potential New Targets for Therapy

Contact Info

Product

Resources

About