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

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.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Condition:   Refractory/Relapsed Autoimmune Hemolytic Anemia Intervention:   Drug: Ibrutinib Sponsor:   Institute of Hematology & Blood Diseases Hospital Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Authors: Su J, Bylsma LC, Jiang X, Morales Arias J, Jain N, Nordyke RJ Abstract Aims: Cold agglutinin disease (CAD) is a rare subtype of autoimmune hemolytic anemia associated with increased thromboembolism risk and early mortality. Healthcare resource utilization (HRU) in CAD has not been reported. We aimed to compare HRU of patients with CAD with a matched non-CAD cohort in the United States.Materials and Methods: Patients with CAD were identified from 2006 to 2016 in the Optum-Humedica database using CAD terms in clinical notes and hematologist review. Patients were required to have Integrated Delivery Network r...
Source: Journal of Medical Economics - Category: Health Management Tags: J Med Econ Source Type: research
Conclusion: The miRNA-mRNA network in our study show that hsa-mir-34a-5p, hsa-mir-195-5p, and hsa-mir-424-5p may regulate the T cell differentiation and plasticity by targeting histone gene expression and histone modification. PMID: 32338587 [PubMed - in process]
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ systems. Patients can have hematologic manifestations, including Evans syndrome (ES), which is characterized by immune-mediated thrombocytopenia and anemia. The association of neurofibromatosis 1 (NF1) with autoimmune disorders is rarely reported. We will review the literature for this combination of disorders and describe a case of a 16-year-old girl who presents with immune-mediated cytopenias and is diagnosed with SLE, ES, and NF1. There are 7 reported cases of SLE and NF1 and only 2 are pediatric cases. There are no reports of the c...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Clinical and Laboratory Observations Source Type: research
AbstractThrombotic microangiopathy (TMA) is generally diagnosed through clinical features characterized as microangiopathic hemolytic anemia, thrombocytopenia, and multiple organ injury, as well as by pathological findings such as vascular damage and endothelial cell injury. Rheumatic and autoimmune diseases could be accompanied by secondary TMA; in fact, systemic lupus erythematosus (SLE) is a common disease associated with secondary TMA, and SLE complicated with TMA has been reported to have a poor prognosis. Although TMA occurs rarely in pediatric SLE patients, it often leads to severe clinical conditions. Here, we repo...
Source: CEN Case Reports - Category: Urology & Nephrology Source Type: research
Authors: Barcellini W, Giannotta J, Fattizzo B Abstract Introduction: Autoimmune hemolytic anemia (AIHA) is due to autoantibodies against erythrocytes that may arise either because of primary tolerance breakage or along with several associated conditions, including genetic predispositions, congenital syndromes, environmental triggers, autoimmune diseases, immunodeficiencies, and neoplasms.Areas covered: This review evaluated the risk of AIHA development in associated conditions and summarized disease-intrinsic risk factors for relapse and outcome. Diagnostic procedures were analyzed to properly identify primary and...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research
We report three patients who developed lichen sclerosus et atrophicus superimposed on skin involved by scleredema adultorum of Buschke. Although the association of lichen sclerosus et atrophicus with scleredema adultorum of Buschke could be coincidental, both diseases could be considered part of the spectrum of sclerodermoid disorders with common underlying pathogenetic mechanisms; which could explain the sequential or simultaneous occurrence of both lesions in our patients.
Source: Indian Journal of Dermatology, Venereology and Leprology - Category: Dermatology Authors: Source Type: research
We report here a rare case of post-transplant lymphoproliferative disorder (PTLD) associated with Epstein–Barr virus (EBV) reactivation in a 30-year-old female patient who underwent allogeneic HSCT for severe aplastic anemia. The PTLD, which was diagnosed 230 days after transplantation, was localized exclusively in the central nervous system (specifically in the choroid plexus) and manifested with obvious signs of intracranial hypertension. After receiving three cycles of high dose methotrexate (HD-MTX) combined with rituximab, the patient achieved a complete clinical recovery with normalization of blood cell cou...
Source: Viruses - Category: Virology Authors: Tags: Case Report Source Type: research
AbstractPrimary familial brain calcification (PFBC) is a well-known genetic condition that has recently had a surge of autosomal recessive cases. We recently reported a case of autosomal recessive PFBC on a 54-year-old Brazilian patient with a novel homozygous variant onMYORG. Interestingly, that patient also had a series of uncommon signs and symptoms, including Hashimoto ’s thyroiditis, polyneuropathy, optic nerve head drusen (ONHD), and persistent anemia. We chose to perform whole exome sequencing (WES) to possibly detect other unknown genetic conditions that could explain the extra-neurological findings reported....
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research
Autoimmune hemolytic anemia (AIHA) has been reported after treatment with an anti-CD52 monoclonal antibody (alemtuzumab) in 7 MS cases.1 All underwent positive direct Coombs test, i.e., antibodies to red blood cells (RBCs); however, no autoantibody (Ab) specificity was identified.1 Aquaporin 1 (AQP1), expressed in RBCs2 and human astrocytes,3,4 has been linked with autoimmunity: in some AIHA cases (Abs to Colton group antigens located on AQP1)2 and in some patients with CNS demyelinating disorders.3,4 Therefore, AQP1-Abs deserve investigation as the possible linking cause of the concurrent presence of the 2 disorders. Here...
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Autoimmune diseases, Multiple sclerosis, Devic's syndrome Clinical/Scientific Notes Source Type: research
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