Human leucocyte antigens A, B, C, and DRW in idiopathic "warm" autoimmune haemolytic anaemia.

Abdel-Khalik, A; Paton, Louise N.; White, A. C.; Urbaniak, S. J.

doi:10.1136/bmj.280.6216.760

Cited by 16 publications

(4 citation statements)

References 6 publications

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“…Although not specifically involved in the changing landscape of AIHA, it is worth considering genetic factors and historically recognized exogenous triggers (4). Several old and recent studies demonstrated a strong association of AIHA with HLA-B locus, particularly HLA-B8 and BW6 (21), or a reduced frequency of the disease in subjects harboring the HLA-DQ6 locus (22) (Table 2). As regards humoral immune response, various variable regions of the immunoglobulin heavy and light chains (IGHV and IGKV) have been associated with AIHA, particularly IGHV4-34, IGHV3, and IGKV3-20 genes, responsible for I antigen binding, and mostly represented in CAD (6).…”

Section: Genetic Background and Exogenous Triggers For Aiha Developmentmentioning

confidence: 99%

The Changing Landscape of Autoimmune Hemolytic Anemia

Barcellini

Fattizzo

2020

Front. Immunol.

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Autoimmune hemolytic anemia (AIHA) is a greatly heterogeneous disease due to autoantibodies directed against erythrocytes, with or without complement activation. The clinical picture ranges from mild/compensated to life-threatening anemia, depending on the antibody's thermal amplitude, isotype and ability to fix complement, as well as on bone marrow compensation. Since few years ago, steroids, immunesuppressants and splenectomy have been the mainstay of treatment. More recently, several target therapies are increasingly used in the clinical practice or are under development in clinical trials. This has led to the accumulation of refractory/relapsed cases that often represent a clinical challenge. Moreover, the availability of several drugs acting on the different pathophysiologic mechanisms of the disease pinpoints the need to harness therapy. In particular, it is advisable to define the best choice, sequence and/or combination of drugs during the different phases of the disease. In particular relapsed/refractory cases may resemble pre-myelodysplastic or bone marrow failure syndromes, suggesting a careful use of immunosuppressants, and vice versa advising bone marrow immunomodulating/stimulating agents. A peculiar setting is AIHA after autologous and allogeneic hematopoietic stem cell transplantation, which is increasingly reported. These cases are generally severe and refractory to standard therapy, and have high mortality. AIHAs may be primary/idiopathic or secondary to infections, autoimmune diseases, malignancies, particularly lymphoproliferative disorders, and drugs, further complicating their clinical picture and management. Regarding new drugs, the false positivity of the Coombs test (direct antiglobulin test, DAT) following daratumumab adds to the list of difficult diagnosis, together with the passenger lymphocyte syndrome after solid organ transplants. Diagnosis of DAT-negative AIHAs and evaluation of disease-related risk factors for relapse and mortality, notwithstanding improvement in diagnostic approach, are still an unmet need. Finally, AIHA is increasingly described following therapy of solid cancers with inhibitors of immune checkpoint molecules. On the whole, the double-edged sword of new pathogenetic insights and therapies has changed the landscape of AIHA, both providing enthusiastic knowledge and complicating the clinical management of this disease.

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Section: Genetic Background and Exogenous Triggers For Aiha Developmentmentioning

confidence: 99%

The Changing Landscape of Autoimmune Hemolytic Anemia

Barcellini

Fattizzo

2020

Front. Immunol.

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“…The genetic background plays an important role. AIHA has been associated with HLA-B8 and BW6 locus, with a particular configuration of the variable region of the immunoglobulin heavy and light chains (IGHV and IGKV), and with polymorphism of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene [26]. More recently, mutations of KMT2D and CARD11 genes have been reported in 69% and 31% of CAD patients [27].…”

Section: Genetic Background In Aiha Pathogenesismentioning

confidence: 99%

New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy

Barcellini

Zaninoni

Giannotta

et al. 2020

JCM

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Autoimmune hemolytic anemia (AIHA) is a highly heterogeneous disease due to increased destruction of autologous erythrocytes by autoantibodies with or without complement involvement. Other pathogenic mechanisms include hyper-activation of cellular immune effectors, cytokine dysregulation, and ineffective marrow compensation. AIHAs may be primary or associated with lymphoproliferative and autoimmune diseases, infections, immunodeficiencies, solid tumors, transplants, and drugs. The direct antiglobulin test is the cornerstone of diagnosis, allowing the distinction into warm forms (wAIHA), cold agglutinin disease (CAD), and other more rare forms. The immunologic mechanisms responsible for erythrocyte destruction in the various AIHAs are different and therefore therapy is quite dissimilar. In wAIHA, steroids represent first line therapy, followed by rituximab and splenectomy. Conventional immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporine) are now considered the third line. In CAD, steroids are useful only at high/unacceptable doses and splenectomy is uneffective. Rituximab is advised in first line therapy, followed by rituximab plus bendamustine and bortezomib. Several new drugs are under development including B-cell directed therapies (ibrutinib, venetoclax, parsaclisib) and inhibitors of complement (sutimlimab, pegcetacoplan), spleen tyrosine kinases (fostamatinib), or neonatal Fc receptor. Here, a comprehensive review of the main clinical characteristics, diagnosis, and pathogenic mechanisms of AIHA are provided, along with classic and new therapeutic approaches.

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“…Human patients with AIHA have been reported to have increased frequencies of the HLA class I alleles, B8, (36) and B27 (37), and also reduced frequency of HLA‐DQ6 (38, 39). There are no other reports of studies on HLA class II for human AIHA, so these class I associations may reflect linkage with other MHC genes.…”

Section: Introductionmentioning

confidence: 99%

Association of a common dog leucocyte antigen class II haplotype with canine primary immune‐mediated haemolytic anaemia

et al. 2006

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Immune-mediated haemolytic anaemia (IMHA) is the commonest immune-mediated disease of the dog, representing a major health concern to this species. The aim of this investigation was to determine whether genetic susceptibility to IMHA is associated with genes of the canine major histocompatibility complex (MHC; dog leucocyte antigen system, DLA). Samples were collected from 108 dogs with primary idiopathic, Coombs' positive IMHA. This diseased population was subdivided on the basis of Coombs' test results into two groups: 1) dogs with dominant warm-reactive immunoglobulin (Ig) G haemagglutinins and (2) dogs with an additional or dominant cold-reactive IgM haemagglutinin. The DLA class II alleles and haplotypes of the diseased population were characterised, and these data were compared with those derived from a breed-matched control cohort and a much larger group of DLA-typed dogs. Two haplotypes were increased in the patient group: DLA-DRB1*00601/DQA1*005011/DQB1*00701 (in the group with warm-reactive IgG haemagglutinins only) and DLA-DRB1*015/DQA1*00601/DQB1*00301 (in both groups, but more so in the group with cold-reactive IgM haemagglutinins). One haplotype, DLA-DRB1*001/DQA1*00101/DQB1*00201, was decreased in the total patient group, but this decrease was limited to the warm-reactive IgG haemagglutinins group, and it was actually increased in the cold-reactive IgM haemagglutinins group. A second haplotype, DLA-DRB1*015/DQA1*00601/DQB1*02301, was also decreased in the total patient group, and this decrease was found in both subgroups. In addition, all haplotypes carrying DLA-DRB1*001 were significantly increased in the cold-reactive IgM haemagglutinins group. When the overall patient group was divided on the basis of individual breeds with more than six animals represented, each of the haplotypes could be shown to be implicated in one of the breeds. Thus, it was apparent that different breeds had different MHC associations with canine IMHA, which is similar to the observation that different human ethnic groups can have different HLA associations with the same immune-mediated disease.

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Human leucocyte antigens A, B, C, and DRW in idiopathic "warm" autoimmune haemolytic anaemia.

Cited by 16 publications

References 6 publications

The Changing Landscape of Autoimmune Hemolytic Anemia

The Changing Landscape of Autoimmune Hemolytic Anemia

New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy

Association of a common dog leucocyte antigen class II haplotype with canine primary immune‐mediated haemolytic anaemia

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