Clinical severity in adult warm autoimmune hemolytic anemia and its relationship to antibody specificity

Chadebech, Philippe; Loustau, Valentine; Janvier, D.; Languille, Laetitia; Ripa, Julie; Tamagne, Marie; Bierling, Philippe; Djoudi, Rachid; Godeau, Bertrand; Michel, Marc; Mahévas, Matthieu

doi:10.3324/haematol.2017.175976

Cited by 3 publications

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As more studies were undertaken to obtain a better understanding of the specificities of warm autoantibodies, it became apparent that band 3 on RBCs was involved and possibly a main target of these autoantibodies [13][14][15]. Subsequent publications began to support the idea that band 3 was a major target of warm autoantibodies [16][17][18][19]. It is now generally acknowledged that the main specificity of warm autoantibodies is to components of band 3 [19].…”

Section: Specificity Of Autoantibodiesmentioning

confidence: 99%

Warm autoimmune hemolytic anemia: new insights and hypotheses

Branch

2023

Current Opinion in Hematology

View full text Add to dashboard Cite

Purpose of review Warm autoimmune hemolytic anemia (wAIHA) is the most common of the immune hemolytic anemias. Although there are numerous case reports and reviews regarding this condition, some of the unusual and more recent findings have not been fully defined and may be contentious. This review will provide insight into the common specificity of the warm autoantibodies and hypothesize a novel mechanism of wAIHA, that is proposed to be linked to the controversial subject of red blood cell senescence. Recent findings and hypotheses It is now well established that band 3 on the red blood cell is the main target of autoantibodies in wAIHA. wAIHA targets the older red blood cells (RBCs) in about 80% of cases and, recently, it has been shown that the RBCs in these patients are aging faster than normal. It has been proposed that in these 80% of patients, that the autoantibody recognizes the senescent red blood cell antigen on band 3. It is further hypothesized that this autoantibody's production and potency has been exacerbated by hypersensitization to the RBC senescent antigen, which is processed through the adaptive immune system to create the pathogenic autoantibody. Recent publications have supported previous data that the senescent RBC antigen is exposed via a dynamic process, wherein oscillation of a band 3 internal loop flipping to the cell surface, creates a conformational neoantigen that is the RBC senescent antigen. It has also recently been shown that the cytokine profile in patients with wAIHA favors production of inflammatory cytokines/chemokines that includes interleukin-8 which can activate neutrophils to increase the oxidative stress on circulating RBCs to induce novel antigens, as has been postulated to favour exposure of the senescent RBC antigen. Summary This manuscript reviews new findings and hypotheses regarding wAIHA and proposes a novel mechanism active in most wAIHA patients that is due to an exacerbation of normal RBC senescence.

show abstract

Section: Specificity Of Autoantibodiesmentioning

confidence: 99%

Warm autoimmune hemolytic anemia: new insights and hypotheses

Branch

2023

Current Opinion in Hematology

View full text Add to dashboard Cite

show abstract

Autoimmune hemolytic anemia in hospitalized patients

Chen¹,

Wang²,

Han³

et al. 2020

Medicine

View full text Add to dashboard Cite

Autoimmune hemolytic anemia (AIHA) is a rare disease in which autoantibodies target red blood cells (RBCs), leading to anemia that ranges from no symptoms to severe life-threatening hemolysis. Little is known about the severity of anemia, blood transfusion efficiency and risk of transfusion-related reactions among hospitalized AIHA patients, especially in those with incompatible RBC transfusions. A retrospective study was conducted among hospitalized AIHA patients from January 2009 to December 2015 in a large tertiary care medical center in southwest China. A total of 450 AIHA hospitalized patients were recruited, of whom 97.3% had warm AIHA, 30.3% had primary AIHA, and 90.7% were treated with corticosteroids. On admission, approximately 3% of patients had an hemoglobin (Hb) <30 g/L, 34% had an Hb between 30 and 59.9 g/L, and 46% had an Hb ranging from 60 to 89.9 g/L. A total of 2509.5 U RBCs were transfused to AIHA patients, and 14 transfusion-related adverse reactions were recorded, without any hemolytic transfusion reactions. With an average transfusion trigger of 52.0 ± 9.3 g/L, 59.7% of the patients received RBCs, and 55.8% of the transfusions were viewed as effective. Least incompatible RBCs were given in 39% of the transfusions, but the transfusion efficiency did not significantly decrease with these incompatible blood transfusions (P = .253). Primary AIHA patients with a nadir Hb of approximately 40 to 50 g/L during their hospital stay had the highest rate of remission and did not require a different total number of RBC transfusions (P = .068) or length of hospitalization (P = .194) compared to other groups with nadir Hb values <30 g/L, ≥30 and <40 g/L, ≥50 and <60 g/L, and ≥60 g/L. One-third of AIHA patients suffered from severe anemia during hospitalization, and transfusions, even with incompatible RBCs, were safe and efficient. However, transfusion triggers between 40 and 50 g/L seemed to benefit the most patients by alleviating the RBC destruction caused by autoantibodies, and a restrictive transfusion strategy was beneficial in AIHA patients.

show abstract

Differential red blood cell age fractionation and Band 3 phosphorylation distinguish two different subtypes of warm autoimmune hemolytic anemia

et al. 2020

View full text Add to dashboard Cite

BACKGROUNDWarm autoimmune hemolytic anemia (wAIHA) is a blood disorder characterized by the increased destruction of autologous red blood cells (RBCs) due to the presence of opsonizing pathogenic autoantibodies. Preliminary reports published more than three decades ago proposed the presence of two wAIHA subtypes: Type I, in which autoantibodies preferentially recognize the oldest, most dense RBCs; and Type II, characterized by autoantibodies that show no preference.STUDY DESIGN AND METHODSWe evaluated patients having wAIHA for Type I and II subtype using discontinuous Percoll gradient age fractionation and direct antiglobulin test (DAT). We performed Western immunoblotting and mass spectrometry to show autoantibody specificity for Band 3. We investigated Band 3 tyrosine phosphorylation in different Percoll fractions to determine aging associated with oxidative stress.RESULTSWe confirm the existence of two subtypes of wAIHA, Type I and Type II, and that autoantibodies recognize Band 3. Type I patients were characterized by five Percoll fractions, with a DAT showing IgG opsonization F1 < F5 and elevated Band 3 phosphorylation compared to healthy controls (HCs). In contrast, Type II wAIHA patients were characterized by three to four Percoll fractions, where the DAT IgG opsonization shows F1 ≥ F3/4 and Band 3 phosphorylation was absent or significantly decreased compared to HC.CONCLUSIONSType I patients have increased Band 3 tyrosine phosphorylation that may represent accelerated aging of their RBCs resulting in exacerbation of a pathologic form of RBC senescence. Type II patients show decreased Band 3 tyrosine phosphorylation and lack the oldest, most dense RBCs suggesting premature RBC clearance and a more severe wAIHA.

show abstract

Clinical severity in adult warm autoimmune hemolytic anemia and its relationship to antibody specificity

Cited by 3 publications

References 14 publications

Warm autoimmune hemolytic anemia: new insights and hypotheses

Warm autoimmune hemolytic anemia: new insights and hypotheses

Autoimmune hemolytic anemia in hospitalized patients

Differential red blood cell age fractionation and Band 3 phosphorylation distinguish two different subtypes of warm autoimmune hemolytic anemia

Contact Info

Product

Resources

About