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

Bloch, Evgenia M.; Branch, Haley A.; Sakac, Darinka; Leger, Regina M.; Branch, Donald R.

doi:10.1111/trf.15911

Cited by 3 publications

(17 citation statements)

References 48 publications

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“…Those patients showing no difference or even slightly more reactivity with reticulocyte-enriched RBCs, were called Type II and patients as having Type II wAIHA. Other reports have supported these observations [1,19].…”

Section: Warm Autoantibodies Preferencially React With Old Red Blood ...mentioning

confidence: 57%

“…Recently, these two specificities of warm autoantibodies were confirmed in 22 patients having wAIHA using discontinuous Percoll gradients to separate reticulocyte-enriched vs. older RBCs [19]. These investigators also showed by Western blot and LC-MS that the warm autoantibodies were reacting with band 3 on the RBCs [19].…”

Section: Key Pointsmentioning

confidence: 83%

“…Band 3 phosphorylation is a hallmark of aged RBCs [59,60]. Investigators have suggested that these results may show that Type I wAIHA represents an exacerbation of normal RBC senescence [1,19,30,49] ] plays a role in the increased in vivo aging in Type I wAIHA requires further investigation.…”

Section: Type I Warm Autoimmune Hemolytic Anemia Antibody Reacts With...mentioning

confidence: 98%

“…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%

“…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]. It is important to note that glycophorin A and Rh blood group antigens are linked to band 3, and that the Wright antigen lies on band 3 [20].…”

Section: Specificity Of Autoantibodiesmentioning

confidence: 99%

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Warm autoimmune hemolytic anemia: new insights and hypotheses

Branch

2023

Current Opinion in Hematology

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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.

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Section: Warm Autoantibodies Preferencially React With Old Red Blood ...mentioning

confidence: 57%

Section: Key Pointsmentioning

confidence: 83%

Section: Type I Warm Autoimmune Hemolytic Anemia Antibody Reacts With...mentioning

confidence: 98%

Section: Specificity Of Autoantibodiesmentioning

confidence: 99%

Section: Specificity Of Autoantibodiesmentioning

confidence: 99%

See 3 more Smart Citations

Warm autoimmune hemolytic anemia: new insights and hypotheses

Branch

2023

Current Opinion in Hematology

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Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management

Loriamini,

Cserti-Gazdewich,

Branch

2024

IJMS

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: Autoimmune hemolytic anemias (AIHAs) are conditions involving the production of antibodies against one’s own red blood cells (RBCs). These can be primary with unknown cause or secondary (by association with diseases or infections). There are several different categories of AIHAs recognized according to their features in the direct antiglobulin test (DAT). (1) Warm-antibody AIHA (wAIHA) exhibits a pan-reactive IgG autoantibody recognizing a portion of band 3 (wherein the DAT may be positive with IgG, C3d or both). Treatment involves glucocorticoids and steroid-sparing agents and may consider IVIG or monoclonal antibodies to CD20, CD38 or C1q. (2) Cold-antibody AIHA due to IgMs range from cold agglutinin syndrome (CAS) to cold agglutin disease (CAD). These are typically specific to the Ii blood group system, with the former (CAS) being polyclonal and the latter (CAD) being a more severe and monoclonal entity. The DAT in either case is positive only with C3d. Foundationally, the patient is kept warm, though treatment for significant complement-related outcomes may, therefore, capitalize on monoclonal options against C1q or C5. (3) Mixed AIHA, also called combined cold and warm AIHA, has a DAT positive for both IgG and C3d, with treatment approaches inclusive of those appropriate for wAIHA and cold AIHA. (4) Paroxysmal cold hemoglobinuria (PCH), also termed Donath–Landsteiner test-positive AIHA, has a DAT positive only for C3d, driven upstream by a biphasic cold-reactive IgG antibody recruiting complement. Although usually self-remitting, management may consider monoclonal antibodies to C1q or C5. (5) Direct antiglobulin test-negative AIHA (DAT-neg AIHA), due to IgG antibody below detection thresholds in the DAT, or by non-detected IgM or IgA antibodies, is managed as wAIHA. (6) Drug-induced immune hemolytic anemia (DIIHA) appears as wAIHA with DAT IgG and/or C3d. Some cases may resolve after ceasing the instigating drug. (7) Passenger lymphocyte syndrome, found after transplantation, is caused by B-cells transferred from an antigen-negative donor whose antibodies react with a recipient who produces antigen-positive RBCs. This comprehensive review will discuss in detail each of these AIHAs and provide information on diagnosis, pathophysiology and treatment modalities.

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Flow Cytometry Characterization and Analysis of Glial and Immune Cells from the Spinal Cord

Coser,

Comelis,

Matoso

et al. 2024

Neuroglia

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Several protocols have been developed with the aim of characterizing glial and immune cells from the central and peripheral nervous systems. However, a small number of these protocols have demonstrated the ability to yield satisfactory results following conventional isolation. Considering this necessity and the difficulties encountered in enzymatic and bead isolation, our work proposes a method for the isolation of glial and immune cells from the spinal cord utilizing a Percoll gradient. For this purpose, C57BL/6J spinal cords were dissected, and the lumbar intumescence was dissociated and subjected to a Percoll gradient centrifugation (70%, 50%, 37%, and 10%). Each layer was then separated and labeled for astrocytes (anti-GFAP, TNF-α, IFN-γ, IL-10, IL-4), microglia (anti-CD45, CD11b, CD206, CD68, TNF-α, IFN-γ), and lymphocytes (anti-CD3, CD4, IFN-γ, IL-4). The gate detections were mathematically performed by computational analysis utilizing the K-means clustering algorithm. The results demonstrated that astrocytes were concentrated at the Percoll 10/37 interface, microglia at the Percoll 37/50 layer, and lymphocytes at the Percoll 50/70 layer. Our findings indicate that astrocytes in healthy animals are putative of the A1 profile, while microglia and lymphocytes are more frequently labeled with M1 and Th1 markers, suggesting a propensity towards inflammatory responses. The computational method enabled the semi-autonomous gate detection of flow cytometry data, which might facilitate and expedite the processing of large amounts of data.

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

Cited by 3 publications

References 48 publications

Warm autoimmune hemolytic anemia: new insights and hypotheses

Warm autoimmune hemolytic anemia: new insights and hypotheses

Autoimmune Hemolytic Anemias: Classifications, Pathophysiology, Diagnoses and Management

Flow Cytometry Characterization and Analysis of Glial and Immune Cells from the Spinal Cord

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