This study describes the frequency of serum organ-specific and organ-nonspecific autoantibodies in 157 patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). Forty-two age- and gender-matched volunteers were used as controls. We found that patients with NI-CINA had increased frequency of antinuclear antibodies (ANA) compared to controls (33.1 vs. 9.5%, p = 0.0025), and that ANA positivity inversely correlated with the number of circulating neutrophils (r = –0.2765, p < 0.0001). Speckled pattern of reactivity was seen in 84.6% of ANA-positive patients, and diffuse pattern in the remaining 15.4%. Patients had also increased levels of circulating immune complexes compared to controls (3.30 ± 2.41 vs. 1.70 ± 1.19 µg/ml, p = 0.0042), which inversely correlated with the number of circulating neutrophils (r = –0.2405, p = 0.0154) but not with the titer of ANA positivity. No significant differences were found between the patients and the normal controls in the frequency of positive tests for antibodies to dsDNA, Sm, nRNP, SSA, SSB and Scl-70 antigens, or for parietal cell antibodies, anti-neutrophil cytoplasmic antibodies (ANCA), anti-cardiolipin and anti-thyroid antibodies. Serum levels of rheumatoid factor, C-reactive protein (CRP) and complement factors C3 and C4 ranged within normal limits in the patients studied, but a highly significant correlation was noted between the levels of CRP and ANA positivity (r = 0.3936, p < 0.0001). These findings are suggestive of a chronic inflammation in NI-CINA patients which provides the antigenic stimulus for ANA production, and they further support our previously reported suggestion for the possible involvement of such a low-grade chronic inflammatory process in the pathogenesis of neutropenia in the affected subjects.

1.
Kyle RA, Linman JW: Chronic idiopathic neutropenia. N Engl J Med 1968;279:1015–1019.
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.
3.
Haddy TB, Rana SR, Castro O: Benign ethnic neutropenia: What is a normal absolute neutrophil count? Lab Clin Med 1999;133:15–22.
4.
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.
5.
Papadaki HA, Eliopoulos GD: Selective loss of peripheral blood CD45RO-positive T lymphocytes correlates with increased levels of serum cytokines and endothelial cell-derived cell adhesion molecules in patients with chronic idiopathic neutropenia of adults. Ann Hematol 1998;77:153–159.
6.
Papadaki HA, Coulocheri S, 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.
7.
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-β1 by bone marrow stromal cells. Eur J Haematol 1999;63:154–162.
8.
Papadaki HA, Chatzivassili A, Stefanaki K, Koumaki V, Kanavaros P, Eliopoulos GD: Morphologically defined myeloid cell compartments, lymphocyte subpopulations and histological findings of bone marrow in patients with nonimmune chronic idiopathic neutropenia of adults. Ann Hematol 2000;79:563–570.
9.
Papadaki HA, Palmblad J, Kapsimali V, Anagnou NP, Eliopoulos GD: Increased serum IgA and decreased IgG3 strongly correlate with increased serum levels of TGF-β1 in patients with nonimmune chronic idiopathic neutropenia of adults. Eur J Haematol 2000;65:237–244.
10.
Papadaki HA, Eliopoulos DG, Ponticoglou C, Eliopoulos GD: Increased frequency of monoclonal gammopathy of undetermined significance in patients with nonimmune chronic idiopathic neutropenia of adults. Int J Haematol, submitted.
11.
Papadaki HA, Katrinakis G, Eliopoulos AG, Coulocheri SA, Alexandrakis M, Eliopoulos GD: Low numbers of peripheral blood natural killer cells in patients with chronic idiopathic neutropenia of adults is probably due to enhanced extravasation into the tissues. Haema 1998;1:32–39.
12.
Hoffbrand AV, Pettit JE: Essential Haematology, ed 3. Oxford, Blackwell Scientific, 1993.
13.
Goodwin JS, Searles RP, Tung KS: Immunological responses of healthy elderly population. Clin Exp Immunol 1982;48:403–410.
14.
Craig WY, Ledue TB, Johnson AM, Ritchie RF: The distribution of antinuclear antibody titers in ‘normal’ children and adults. J Rheumatol 1999;26:914–919.
15.
Davis JS: Antinuclear antibodies; in Kelley WN, et al (eds): Textbook of Rheumatology. London, Saunders, 1981, pp 691–709.
16.
Chou MJ, Lee SL, Chen TY, Tsay GJ: Specificity of antinuclear antibodies in primary biliary cirrhosis. Ann Rheum Dis 1995;54:148–151.
17.
Konikoff F, Isenberg DA, Barrison I, Theodor E, Shoenfeld Y: Antinuclear autoantibodies in chronic live diseases. Hepatogastroenterology 1989;36:341–345.
18.
Hemmerich P, Neu E, Macht M, Peter HH, Krawinkel U, von Mikecz A: Correlation between chlamydial infection and autoimmune response: Molecular mimicry between RNA polymerase major sigma subunit from Chlamydia trachomatis and human L7. Eur J Immunol 1998;28:3857–3866.
19.
Saebo A, Lassen J: Yersinia enterocolitica: An inducer of chronic inflammation. Int J Tissue React 1994;16:51–57.
20.
Czaja AJ, Carpenter HA, Santrach PJ, Moore SB: Immunologic features and HLA associations in chronic viral hepatitis. Gastroenterology 1995;108:157–164.
21.
Wutzler P, Farber I, Ulbricht A: Autoantibodies in herpesvirus infections (letter). Acta Virol 1978;22:342.
22.
Goebel KM, Krause A, Neurath F: Acquired transient autoimmune reactions in Lyme arthritis: Correlation between rheumatoid factor and disease activity. Scand J Rheumatol Suppl 1988;75:314–317.
23.
Rapoport BL, Morrison RC, Sher R, Dos Santos L: A study of autoantibodies in chronic mycobacterial infections. Int J Lepr Other Mycobact Dis 1990;58:518–525.
24.
Garcia-de la Torre I: Autoimmune phenomena in leprosy, particular antinuclear antibodies and rheumatoid factor. J Rheumatol 1993;20:900–903.
25.
Blomgren SE, Condemi JJ, Bignall MC, Vaughan JH: Antinuclear antibody induced by procainamide. A prospective study. N Engl J Med 1969;28:64–66.
26.
Reichlin M, Harley JB: Antinuclear antibodies: An overview; in Wallace DJ, Hahn BH (eds): Dubois Lupus Erythematosus, ed 4. London, Lea & Febiger, 1993, pp 166–194.
27.
Jacob L, Tron F, Bach JF, Louvard D: A monoclonal anti-DNA antibody also binds to cell-surface protein(s). Proc Natl Acad Sci USA 1984;81:3843–3845.
28.
Kabat EA, Liao J, Bretting H, Franklin EC, Geltner D, Frangione B, Koshland ME, Shyong J, Osserman EF: Human monoclonal macroglobulins with specificity for Klebsiella K polysaccharides that contain 3,4-pyruvylated-D-galactose and 4,6-pyruvylated-D-galactose. J Exp Med 1980;152:979–995.
29.
Eilat D, Hochberg M, Pumphrey J, Rudikoff S: Monoclonal antibodies to DNA and RNA from NZB/NZW F1 mice: Antigenic specificities and NH2 terminal amino acid sequences. J Immunol 1984;133:489–494.
30.
Mevorach D, Zhou JL, Song X, Elkon KB: Systemic exposure to irradiated apoptotic cells induces autoantibody production. J Exp Med 1998;188:387–392.
31.
Herrmann M, Voll RE, Zoller OM, Hagenhofer M, Ponner BB, Kalden JR: Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 1998;41:1241–1250.
32.
Adebajo AO, Charles P, Maini RN, Hazleman BL: Autoantibodies in malaria, tuberculosis and hepatitis in a west African population. Clin Exp Immunol 1993;92:73–76.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.