Two‐Step Mechanism of Virus‐induced Autoimmune Hemolytic Anemia

Coutelier, Jean‐Paul; Detalle, Laurent; Musaji, Andrei; Meité, M; Izui, Shozo

doi:10.1196/annals.1398.018

Cited by 13 publications

(10 citation statements)

References 32 publications

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“…[4][5][6] However, in the primary form of AIHA, no inciting cause is identified. 7 The basic pathogenesis of primary AIHA is poorly understood, but clearly results from a failure of tolerance mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundBreakdown of humoral tolerance to RBC antigens may lead to autoimmune hemolytic anemia, a severe and sometimes fatal disease. The underlying mechanisms behind the breakdown of humoral tolerance to RBC antigens are poorly understood. Design and MethodsIn order to study the pathogenesis of autoimmune hemolytic anemia, we developed a murine model with RBC-specific expression of a model antigen carrying epitopes from hen egg lysozyme and ovalbumin. ResultsHumoral tolerance was observed; this was not broken even by strong immunogenic stimulation (lysozyme or ovalbumin with adjuvant). Autoreactive CD4 + T cells were detected by tetramer enrichment assays, but failed to activate or expand despite repeat stimulation, indicating a nonresponsive population rather than deletion. Adoptive transfer of autoreactive CD4 + T cells (OT-II mice) led to autoantibody (anti-lysozyme) production by B cells in multiple anatomic compartments, including the bone marrow. ConclusionsThese data demonstrate that B cells autoreactive to RBC antigens survive in healthy mice with normal immune systems. Furthermore, autoreactive B cells are not centrally tolerized and are receptive to T-cell help. As the autoreactive T cells are present but non-responsive, these data indicate that factors that reverse T-cell non-responsiveness may be central to the pathogenesis of autoimmune hemolytic anemia.Key words: tolerance, B cells, T cells, erythrocyte-specific, self-antigen.Citation: Hudson KE, Hendrickson JE, Cadwell CM, Iwakoshi NN, and Zimring JC. Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice. Haematologica 2012;97(12):1836-1844. doi:10.3324/haematol.2012 This is an open-access paper. Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n

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Section: Introductionmentioning

confidence: 99%

Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice

et al. 2012

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“…Strong evidence has been reported that LDV exacerbates diseases, such as thrombocytopenia and hemolytic anemia by increasing the uptake of target cells by macrophages [1][2][3][4]. Although platelets or erythrocytes are most often ingested after opsonization with IgG autoantibodies, LDV infection alone may also result in antibody-independent thrombocytopenia [15].…”

Section: Discussionmentioning

confidence: 99%

“…Mouse infection with the lactate dehydrogenase-elevating virus (LDV) has been shown to exacerbate autoimmune diseases, such as antibody-mediated anemia [1,2] and thrombocytopenia [3,4]. This effect of LDV infection can be explained by the enhanced phagocytic activity of macrophages [1,3], thus leading to the engulfment and destruction of opsonized cells in response to the macrophage activation, which is mostly triggered by the gammainterferon (IFN-γ) secreted by natural killer cells upon infection [5].…”

Section: Introductionmentioning

confidence: 99%

Involvement of Virus-Induced Interferon Production in IgG Autoantibody-Mediated Anemia

Legrain

Gaignage

et al. 2021

IJMS

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Infection with viruses, such as the lactate dehydrogenase-elevating virus (LDV), is known to trigger the onset of autoimmune anemia through the enhancement of the phagocytosis of autoantibody-opsonized erythrocytes by activated macrophages. Type I interferon receptor-deficient mice show enhanced anemia, which suggests a protective effect of these cytokines, partly through the control of type II interferon production. The development of anemia requires the expression of Fcγ receptors (FcγR) I, III, and IV. Whereas LDV infection decreases FcγR III expression, it enhances FcγR I and IV expression in wild-type animals. The LDV-associated increase in the expression of FcγR I and IV is largely reduced in type I interferon receptor-deficient mice, through both type II interferon-dependent and -independent mechanisms. Thus, the regulation of the expression of FcγR I and IV, but not III, by interferons may partly explain the exacerbating effect of LDV infection on anemia that results from the enhanced phagocytosis of IgG autoantibody-opsonized erythrocytes.

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“…Of note, antiviral prophylaxis is stopped 6 months post‐LT in our protocol, coinciding with the cases of late IHA, and further putting into question the role of CMV prophylaxis as opposed to pre‐emptive strategies . Although the pathophysiology of IHA is beyond the scope of the present study, genetic diversity of the immune response both to viral triggers and to immunosuppression may act as a cofactor …”

Section: Discussionmentioning

confidence: 99%

Factors associated with immune hemolytic anemia after pediatric liver transplantation

Rock¹,

Ansari

Villard

et al. 2018

Pediatric Transplantation

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Immune-mediated hemolytic anemia following SOT is a rare disorder, the risk factors for which are unknown. Our purpose was to analyze a seemingly increased incidence in our center with the aim to identify predisposing factors. This recipients single-center retrospective study reviewed the medical records of 96 pediatric LT between 2000 and 2013. IHA was defined as acute anemia with a positive direct antiglobulin test. Seven cases of immune-mediated hemolytic anemia were identified (incidence 8.5%). Three cases presented during the first 3 months following LT (early IHA), and 4 presented later (late IHA). All patients with late IHA required rituximab. Using univariate analysis, the following factors were associated with IHA onset: BA (P = .04), younger age (P = .04), and the use of IGL-1 preservation solution (P = .05). Late IHA was associated with viral infections occurring beyond 3 months following LT, younger age, and BA (P = .01). Overall, CMV infection was associated with the development of both early and late IHA: CMV-negative recipients who received an organ from a CMV-positive donor were more likely to develop IHA (P = .035), and de novo CMV infection during the first year post-LT was associated with late IHA (P = .03). IHA is a rare complication following pediatric LT, occurring more frequently in younger patients and patients with an initial diagnosis of BA. CMV-negative recipients and patients who experience a de novo CMV infection in the first year following LT seem particularly vulnerable. IGL-1 preservation solution may be associated with an increased likelihood of developing IHA, a novel finding which warrants further investigation.

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Two‐Step Mechanism of Virus‐induced Autoimmune Hemolytic Anemia

Cited by 13 publications

References 32 publications

Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice

Partial tolerance of autoreactive B and T cells to erythrocyte-specific self-antigens in mice

Involvement of Virus-Induced Interferon Production in IgG Autoantibody-Mediated Anemia

Factors associated with immune hemolytic anemia after pediatric liver transplantation

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