Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil‐specific autoantibodies

Davoren, Anne; Saving, Kay L.; McFarland, Janice G.; Aster, Richard H.; Curtis, Brian R.

doi:10.1111/j.1537-2995.2004.03410.x

Cited by 47 publications

(14 citation statements)

References 26 publications

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“…For these reasons, it is critical that neutrophil antibody and antigen testing be performed by an experienced laboratory using appropriate controls (6,50). The granulocyte agglutination assay (51) and the granulocyte immunofluorescence test by flow cytometry (32,52) are two of the most commonly used serologic assays for neutrophil antibody detection and identification. DNA-based typing of granulocyte antigens HNA-1a, -1b, and -1c is also helpful in confirming alloantigen specificities of neutrophil antibodies detected (53,54).…”

Section: Laboratory Testing For Antibodies In Tralimentioning

confidence: 99%

Mechanisms of transfusion-related acute lung injury (TRALI): Anti-leukocyte antibodies

Curtis

McFarland²

2006

Critical Care Medicine

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There is abundant evidence that leukocyte antibodies in blood donor products are somehow involved in transfusion-related acute lung injury (TRALI). Human leukocyte antigen (HLA) class I, HLA class II, and neutrophil-specific antibodies in the plasma of both blood donors and recipients have been implicated in the pathogenesis of TRALI. The case for a relationship between leukocyte antibodies and TRALI is more compelling if concordance between the antigen specificity of the leukocyte antibodies in the donor plasma and the corresponding antigen on the cells of the affected recipient is demonstrated. Such antibody-antigen concordance can be investigated by typing the recipient for the cognate leukocyte antigens or by cross-matching the donor plasma against the recipient's leukocytes. Two proposed pathophysiologic mechanisms for TRALI have received the most attention: the antibody hypothesis and the two-event hypothesis. The final common pathway in all of the proposed pathogenic mechanisms of TRALI is increased pulmonary capillary permeability, which results in movement of plasma into the alveolar space causing pulmonary edema. A typical TRALI serologic workup consists of tests for HLA class I and II and neutrophil-specific antibodies. The use of flow cytometry and HLA-coated microbeads is recommended for detection of HLA antibodies in plasma of implicated blood donors and a combination of the granulocyte agglutination test and granulocyte immunofluorescence test for detection of neutrophil-specific antibodies. Genotyping for class I and II HLA and for a limited number of neutrophil antigens may also be helpful in establishing antibody-antigen concordance.

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Section: Laboratory Testing For Antibodies In Tralimentioning

confidence: 99%

Mechanisms of transfusion-related acute lung injury (TRALI): Anti-leukocyte antibodies

Curtis

McFarland²

2006

Critical Care Medicine

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“…Immune-mediated neutropenia was suspected, and testing of the patient's serum for neutrophil antibodies was performed using the granulocyte immunofluorescence test by flow cytometry (GIFT-FC) [3,4] against a panel of isolated neutrophils expressing the neutrophil-specific antigens HNA-1a, HNA-1b, HNA-1c, HNA-2, HNA-3a/3b, HNA-4a/b and HNA-5a/b. The patient's serum tested positive for anti-neutrophil antibodies, and characterization of these antibodies [3,4] revealed an immunoglobulin M (IgM) isotype reactive against 4 out of 6 normal donor target neutrophils, but with no specificity for any of the known human neutrophil alloantigens (HNA). Unfortunately, testing of the patient's own neutrophils for autoantibodies was not possible since her ANC was low.…”

Section: Report Of Casementioning

confidence: 99%

Severe autoimmune neutropenia associated with acute autoimmune hepatitis

et al. 2010

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A 49-year-old previously healthy female presented with acute hepatitis and severe neutropenia. A diagnosis of type 1 autoimmune hepatitis was made based on the histological appearance of a liver core biopsy, positive anti-smooth muscle antibodies, and positive anti-neutrophil cytoplasmic antibody (atypical ANCA). Hemogram revealed mild leukopenia with severe neutropenia (absolute neutrophil count 256/mm 3 ), normal hemoglobin and mild thrombocytopenia (115000/mm 3 ). A bone marrow biopsy and aspirate had a normal karyotype, increase in granulopoiesis, prominence of promyelocytes (31%) and absence of mature granulocytes. Anti-neutrophil antibodies were detected in the patient's blood. Therapy was directed at the underlying hepatitis with resolution of neutropenia without the use of colony-stimulating factors.

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“…3,6 Isolation of neutrophils, T and B lymphocytes, and platelets from normal donor blood, detection of antibodies reactive with these cells by flow cytometry and agglutination, and immunoprecipitation of membrane proteins have been described previously. [7][8][9] …”

Section: Antibodies and Antibody Detectionmentioning

confidence: 99%

The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution

Curtis

Cox

Sullivan

et al. 2010

Blood

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IntroductionThe leukocyte antigens 5a and 5b (now designated HNA-3b and HNA-3a) constitute a biallelic antigen system identified by van Leeuwen et al in 1964 using antibodies from multiparous women that agglutinated leukocytes of normal persons. 1 Despite the passage of more than 40 years, molecular properties of the HNA-3 antigens have not been defined. Characterization of HNA-3a has become particularly important with the recognition that HNA-3a-specific antibodies are prone to cause severe, often fatal, transfusion-associated acute lung injury (TRALI). [2][3][4][5] Here, we provide evidence that HNA-3a is carried on choline transporter-like protein 2 (CTL2), a member of the choline transporter-like family of membrane glycoproteins, and that the antigen results from a single nucleotide polymorphism (SNP) in exon 7 of the CTL2 gene (SLC44A2) encoding R154 (HNA-3a) or Q154 (HNA-3b) in the first extracellular loop of the mature protein. Methods Antibodies and antibody detectionHNA-3a-specific antibodies were from donors implicated in TRALI reactions. 3,6 Isolation of neutrophils, T and B lymphocytes, and platelets from normal donor blood, detection of antibodies reactive with these cells by flow cytometry and agglutination, and immunoprecipitation of membrane proteins have been described previously. [7][8][9] SNP analysisGenotyping of DNA from 8 unrelated HNA-3a-negative persons was performed using the Human Genome-Wide SNP Array 6.0 (Affymetrix). Genotypes were assigned using Birdseed 2.0. 10 Quality control studies, including assessment of call rate, investigation of potential genetic relationships among samples, and examination of data to identify potential departures from expected levels of heterozygosity, were completed using plink. 11 Eigenstrat was used to assess geographic ancestry in combination with HapMap CEU, YRI, JPT, and CHB samples. 12 All samples had high call rates (Ͼ 98%) with high-quality genotype data. The 8 HNA-3a-negative persons appeared to be of recent European descent and were quite similar in ancestry to the HapMap CEU samples. Association studies were performed using the 8 HNA-3a-negative samples as cases and unrelated European samples from HapMap3 as controls, with significance assessed using 100 000 permutations; thus, the smallest possible P value in permutation analysis was P ϭ 1 ϫ 10 Ϫ6 . DNA sequencingGenomic DNA was amplified by the polymerase chain reaction using primers designed to amplify exon 7 of the CTL2 gene SLC44A2 (reference sequence National Center for Biotechnology Information database; www.ncbi.nlm.nih.gov/nucore/NM_001145056.1). Primer sequences are available on request. Automated sequence analysis of polymerase chain reaction products was performed in both directions with the Big Dye Terminator version 3.1 Cycle Sequencing kit on an ABI 3130XL genetic analyzer (Applied Biosystems). 13 Mass spectrometryHNA-3a-specific antibody was incubated with HNA-3a-positive leukocytes and subjected to immunoprecipitation. An Inside Blood analysis of this article appears at the fr...

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Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil‐specific autoantibodies

Cited by 47 publications

References 26 publications

Mechanisms of transfusion-related acute lung injury (TRALI): Anti-leukocyte antibodies

Mechanisms of transfusion-related acute lung injury (TRALI): Anti-leukocyte antibodies

Severe autoimmune neutropenia associated with acute autoimmune hepatitis

The neutrophil alloantigen HNA-3a (5b) is located on choline transporter-like protein 2 and appears to be encoded by an R>Q154 amino acid substitution

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