Serological and clinical aspects of granulocyte antibodies leading to alloimmune neonatal neutropenia

Abstract

Eighteen cases of alloimmune neonatal neutropenia (ANN) were analysed for their clinical and serological properties. Pregnancy was normal in all cases, but a 50% incidence of abortion is recorded. With the exception of two premature babies, all newborns were delivered at term. Omphalitis and mild infections of the skin were predominantly present. None of the new-borns died by overwhelming sepsis. The average duration of neutropenia was 11 weeks (range 3-28 weeks). Intravenous IgG therapy was followed by transient remission in 2 of 4 affected newborns. Antibody differentiation revealed in five sera NA1-, in four sera NA2- and in two sera NB1-specific antibodies. In two sera only HLA antibodies were detectable. Complement activating antibodies were determined in 72% of the sera. Screening for granulocyte-specific antibodies in 1016 postpartum sera of unselected women revealed a total of 11 sera (1.1%) reacting selectively with granulocytes, but only four (0.4%) were directed against a known granulocyte-specific antigen. None of the new-born of mothers alloimmunized to granulocyte antigens developed neutropenia, which suggests an incidence of ANN below 0.1%.

Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica)

“…Indirect anti-neutrophil antibodies detection by flow cytometry was agreed on to be the most useful and practical method for identifying the autoimmune neutropenia (AIN) [1,7,9,17,[42][43][44][45][46]. The low sensitivity (74% at first assessment) [45] of this method was recognized by the panel but it was considered, in the respect of diagnostic power, less detrimental than the lower specificity (very high number of false positives) of the direct method [44] (III, V, EO, 9, A). If indirect anti-neutrophil antibody test is positive the diagnosis of AIN is appropriate (EO, 9, A).…”

Diagnosis and management of primary autoimmune neutropenia in children: insights for clinicians

“…Severe infections can be present in about 20% of patients [Bux et al 1992a;Rodwell et al 1996;Curtis et al 2005]. A positive crossmatch between maternal sera and paternal neutrophils confirms the diagnosis.…”

Resistance to Recombinant Human Granulocyte Colony-Stimulating Factor in Neonatal Alloimmune Neutropenia Associated With Anti-Human Neutrophil Antigen-2a (NB1) Antibodies

“…[1][2][3][4][5][6][7][8][9][10][11] During the period of neutropenia, antibiotic treatment is somewhat controversial. Prophylactic antibiotics may be used until the results of 12 rhG-CSF administration is generally very effective in NAN, rapidly increasing the ANC to levels considered safe.…”

“…2,23,24 In the United States, however, one half of all of the cases of NAN are mediated by antibodies that bind to 1 of 3 antigens: HNA-1a (NA1), HNA-1b (NA2), or HNA-2a (NB1). 25 rhG-CSF is known to downregulate the expression of certain neutrophil antigens (eg, antigenic determinants on Fc␥IIIb, such as HNA-1a and -1b), 26 thereby rendering the neutrophils less vulnerable to circulating antibodies.…”