Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

Liu, Bainan; Gu, Wan-Gang

doi:10.1155/2013/561852

Cited by 7 publications

(6 citation statements)

References 59 publications

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“…The value of newly developed molecules including ofatumumab and alemtuzumab [ 54 , 55 ], bortezumib [ 56 ], anti-FcRn [ 57 ], TNT003 (an inhibitor of the serine protease C1 S [ 58 ], peptide inhibitors of C 3 activation [ 59 ], IgG-specific endoglycosidase EndoS [ 60 ], kinase inhibitors [ 61 ], bispecific antibodies [ 62 ], or multivalent antibodies [ 63 ] has not been well examined in AIHA.…”

Section: Treatment Optionsmentioning

confidence: 99%

Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review

Salama

2015

Transfus Med Hemother

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Until now, treatment of primary autoimmune hemolytic anemia of the warm type (wAIHA) is primarily based on immunosuppression. However, many patients do not respond adequately to treatment, and treated patients may develop severe side effects due to uncontrolled, mixed and/or long-lasting immunosuppression. Unfortunately, the newly used therapeutic monoclonal antibodies are unspecific and remain frequently ineffective. Thus, development of a specific therapy for AIHA is necessary. The ideal therapy would be the identification and elimination of the causative origin of autoimmunization and/or the correction or reprogramming of the dysregulated immune components. Blood transfusion is the most rapidly effective measure for patients who develop or may develop hypoxic anemia. Although some effort has been made to guide physicians on how to adequately treat patients with AIHA, a number of individual aspects should be considered prior to treatment. Based on my serological and clinical experience and the analysis of evidence-based studies, we remain far from any optimized therapeutic measures for all AIHA patients. Today, the old standard therapy using controlled steroid administration, with or without azathioprine or cyclophosphamide, is, when complemented with erythropoiesis-stimulating agents, still the most effective therapy in wAIHA. Rituximab or other monoclonal antibodies may be used instead of splenectomy in therapy-refractory patients.

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Section: Treatment Optionsmentioning

confidence: 99%

Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review

Salama

2015

Transfus Med Hemother

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“…7 Rituximab has also been seen to be a successful treatment for IgGmediated AIHA, 8 and -despite its high cost and side effects -is recommended as second-line therapy in steroid-refractory AIHA. Cold (IgM-mediated) AIHA usually does not respond to prednisone.…”

confidence: 99%

Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies

et al. 2015

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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 nwhich leads to remission in 50% of patients. 7 Rituximab has also been seen to be a successful treatment for IgGmediated AIHA, 8 and -despite its high cost and side effects -is recommended as second-line therapy in steroid-refractory AIHA. Cold (IgM-mediated) AIHA usually does not respond to prednisone. In some cases hemolysis can be prevented by protection from cold, but otherwise the therapeutic anti-CD20 antibody rituximab seems to be a promising strategy for treatment of this group of patients, showing a response rate of around 50%. 9,10 In general, patients with mixed AIHA initially respond well to steroids, but usually go on to develop chronic hemolysis. 11,12 To determine the optimal therapy, it is crucial to identify the causative RBC autoantibodies correctly, and to evaluate the presence of anti-RBC IgM autoantibodies in AIHA. However, with the current diagnostic techniques, it can be challenging to detect IgM because of its frequently low avidity. Moreover, a distinction is not routinely made between IgG and IgM in the IAT and can be difficult. We, therefore, studied alternative methods to detect autoantibodies in AIHA, focusing on the detection of IgM. First, we adapted the DAT and IAT to a fluorescence-activated cell sorting (FACS)-based assay, since a similar strategy had previously been shown to be successful for the detection of IgG and C3 on RBC.13-16 Secondly, we studied a method for detecting IgM based on the presence of deposited complement factors on patients' RBC. It is known that IgM activates complement more efficiently than IgG and it has been shown that if a patient's serum induces hemolysis in vitro, this is often caused by anti- RBC IgM 17 . Instigated by this, we studied whether the presence or extent of complement C3 deposition, as routinely measured in the DAT, can indicate the presence of anti-RBC IgM by separating IgG and IgM in the sera from AIHA patients and subsequently testing which fractions of the samples activated complement. Methods Patients' materialFor the FACS-based IAT and DAT studies, anonymized residual samples from patients with AIHA (34 and 50 patients, respectively) were used. The samples were collected in 2013 and 2014 and had been sent in for diagnostic tests to the Dutch reference laboratory for immunohematology and had a positive DAT for at least C3d and positivity in the hemolysin test. For the fractionation/depletion experiments, 16 additional samples were used that were positive for at least C3d in the DAT. Details can be found in Online Supplementary Table S1. The presence of clinical hemolysis was confirmed using the following parameters, if available: low hemoglobin, high lactate dehydrogenase, decreased haptoglobin, increased indirect bilirubin or a confirmed diagnosis by the treating physician.Fractionation of serum or eluate from patients with autoimmune hemolytic anemia AIHA patients' serum, recalcified plasma or eluate was filtered through a 0.22 μm filter before loading 0.5 mL on a 10/30...

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“…Chez l'adulte, 8 sur 11 patients souffrant d'une AHAI réfractaire traités par rituximab ont obtenu une réponse complète avec un recul de près de 2 ans [38], tandis que dans une revue de la littérature, le taux de réponse global au rituximab dans l'AHAI est d'environ 82 % [39]. Barcellini et al [40] ont étudié, au cours d'un essai clinique, l'efficacité d'une dose réduite de rituximab (100 mg toutes les 4 semaines) et observé une réponse globale de 82,6 % à 2 mois, 90 % à 6 et 12 mois, avec respectivement dans les AHAI à Ac chauds et dans les AHAI liées à une agglutinine froide des taux respectivement de 100 et 60 %, respectivement (taux très proche des 54 % retrouvé dans une autre étude chez des patients ayant une agglutinine froide [41]).…”

Section: Anémie Hémolytique Auto-immune (Ahai)unclassified

Indications du rituximab au cours des maladies auto-immunes

2014

La Revue de Médecine Interne

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Immunotherapy Treatments of Warm Autoimmune Hemolytic Anemia

Cited by 7 publications

References 59 publications

Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review

Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review

Complement deposition in autoimmune hemolytic anemia is a footprint for difficult-to-detect IgM autoantibodies

Indications du rituximab au cours des maladies auto-immunes

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