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CORRESPONDENCE Nonimmune chronic idiopathic neutropenia of adults
(NI-CINA) is a frequently seen granulocytic disorder characterized by
the "unexplained" persistent decrease of the number of circulating neutrophils below the lower limit of the normal distribution in a given
ethnic population.1,2 The diagnostic criteria allowing the
identification of the condition among other types of chronic neutropenia are presented elsewhere.3-5 The cause of the
disorder and the underlying mechanisms leading to neutropenia in the
affected subjects are unknown, but recent studies in our laboratory
provided strong evidence for the existence of an unrecognized low-grade chronic inflammatory process in these patients, which may be involved in the pathogenesis of NI-CINA by increasing the production of a
variety of proinflammatory cytokines and chemokines3 and therefore affecting both neutrophil production in bone
marrow4 and neutrophil extravasation in the
periphery.5 Here, we describe a predisposition of
HLA-DRB1*1302 haplotype-carrying individuals to develop
NI-CINA. The study was carried out on 56 NI-CINA patients and 39 healthy
volunteers, all residents of the island of Crete. Venous blood was
collected into vacutainer tubes containing ethylenediaminetetraacetic acid (EDTA) as anticoagulant and used as a DNA source. DNA
extraction was carried out by salting-out technique. For the typing of
HLA alleles, polymerase chain reaction (PCR) was utilized. HLA-A, -B,
and -C alleles were typed using PCR-sequence specific primers (PCR-SSP)
with primer sets provided by PelFreez Clinical systems (Brown Deer,
WI). HLA-DRB1 alleles were typed using the ELPHA high resolution hybridization system provided by Biotest
AG (Dreieich, Germany). HLA-DQB1 and DPB1 alleles were typed
using the InnoLiPa reverse slot blot hybridization system
provided by Murex (Immunogenetics, Zwijndzecht, Belgium).
Results were analyzed with the Yates continuity-corrected chi-square
test using the GraphPad program. We found that the frequency of the HLA-DRB1*1302 haplotype was
21.43% in the group of patients compared to 2.56% in the controls (P = .0199) (Table 1). The relative risk
for the carriers was 8.36. The frequencies of all other HLA haplotypes
did not differ significantly between patients and control subjects.
The clinical and biologic significance of our finding is unknown, but it seems possible that the frequency of the HLA-DRB1*1302 haplotype may have a role in the development of the aforementioned unrecognized low-grade chronic inflammation. Associations of HLA haplotypes with chronic inflammatory processes have already been well documented in a variety of clinical disorders.8 We believe that the increased frequency of the HLA-DRB1*1302 haplotype in NI-CINA patients may indicate the possible genetic basis in the development of such an inflammation, and thus it may predispose the haplotype-carrying subjects to develop the disorder.
Helen A. Papadaki and George D. Eliopoulos
Stavroula A. Coulocheri
Maria Spyropoulou, and Cathrin Stavropoulos-Giokas
References 1. Dale DC, Guerry D, Wewerka J, Bull J, Chusid M. Chronic neutropenia. Medicine (Baltimore) 1979;58:128-144[Medline] [Order article via Infotrieve]. 2. Papadaki HA, Xylouri I, Coulocheri S, Kalmanti M, Kafatos A, Eliopoulos GD. Prevalence of chronic idiopathic neutropenia of adults among an apparently healthy population living on the island of Crete. Ann Hematol. 1999;78:293-297[CrossRef][Medline] [Order article via Infotrieve]. 3. Papadaki HA, Coulocheri SA, Eliopoulos GD. Patients with chronic idiopathic neutropenia of adults have increased serum concentrations of inflammatory cytokines and chemokines. Am J Hematol. 2000;65:271-277[CrossRef][Medline] [Order article via Infotrieve].
4.
Papadaki HA, Giouremou K, Eliopoulos GD.
Low frequency of myeloid progenitor cells in chronic idiopathic neutropenia of adults may be related to increased production of TGF- 5. Papadaki HA, Eliopoulos GD. Enhanced neutrophil extravasation may be a contributing factor in the determination of neutropenia in patients with chronic idiopathic neutropenia of adults. Eur J Haematol. 1998;61:272-277[Medline] [Order article via Infotrieve]. 6. Tongs S, March SGE, Bunce M, et al. HLA class I DNA typing study D. Charron, ed. Genetic Diversity of HLA, Functional and Medical Implications. Paris: EDK Medical and Scientific International Publishers; 1997:119-215.
7.
Saiki RK, Walsh Levenson CH, Erlich HA.
Genetic analysis of amplified DNA with immobilized sequence-specific oligonucleotide probes.
Proc Natl Acad Sci U S A.
1989;86:6230-6234 8. Brostoff J, Scadding GK, Male D, Roit IM. Clinical Immunology. London: Mosby; 1994:2.1-2.14.   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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| Copyright © 2001 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
1 by bone marrow stromal cells.
Eur J Haematol.
1999;63:154-162
