The serum levels of the cytokines involved in the Th17 and Th1 cell commitment are increased in individuals with borderline thrombocytopenia
© Rocha et al.; licensee BioMed Central Ltd. 2013
Received: 20 March 2013
Accepted: 8 April 2013
Published: 12 April 2013
The definition of immune Thrombocytopenia (ITP) as a peripheral blood platelet count less than 100 × 109/L instead of the historical criteria of 150 × 109/L renders subjects with platelets between 100 and 150 × 109/L without a diagnosis. Here, we demonstrated that these subjects have enhanced levels of proinflammatory cytokines linked to Th1 and Th17 cell response, and are more frequently carriers of polymorphisms in genes that code cytokines involved in the commitment of Th1 and Th17 immune response, when compared with controls, similarly to that observed in patients with ITP.
KeywordsThrombocytopenia Th1 and Th17 cytokines IL2- 330 IL1RN VNTR
To the editor
According to the International Working Group consensus panel , primary Immune Thrombocytopenia (ITP) is defined as a peripheral blood platelet count less than 100 × 109/L in the absence of any obvious cause of thrombocytopenia. The recommendation of this value as the threshold for diagnosis of ITP, instead of the historical criteria of 150 × 109/L, was first proposed by Rodeghiero et al. based on the results of Stasi et al. showing that healthy individuals with incidentally discovered platelet count between 100 and 150 × 109/L have a 10-year probability of developing persistent thrombocytopenia of only 6.9% and of developing autoimmune disorders other than ITP of 12%. However, in addition to the fact that this criterion has not been formally validated yet , patients with platelet count between 100 and 150 × 109/L remain without a diagnosis . Recently, our group evaluated the serum cytokine profile of 98 patients with chronic ITP (platelet less than 100 × 109/L)  attending the University Hospital, Universidade Federal de Minas Gerais, Brazil and demonstrated higher levels of Th17 cell-related cytokines, in addition to Th1-associated cytokines in the patients than in blood donor controls. We have also demonstrated  that IL1RN VNTR and IL2- 330 allele polymorphisms were associated with increased concentrations of IL-1β and of IL-2, respectively and were risk factors for chronic ITP. In this study, we compared serum Th1 and Th17 cytokine profile of 28 individuals (13 female and 15 male, mean age 49.2 years, range from 19 to 79 years) with persistent borderline thrombocytopenia with that of chronic ITP patients and controls we have previously evaluated . None of the included individuals had obvious predisposing conditions or factors associated with thrombocytopenia. The platelet count of the subjects ranged from 101 to 138 × 109/L with a mean (±SD) of 120(±10) × 109/L and the duration of the thrombocytopenia varied from one to 12 years with a mean (±SD) of 4.7(±3.6) years. The serum cytokine concentrations (picogram per milliliter, pg/mL) were assayed in duplicate by ELISA (Biosource, Camarillo, CA). This study was approved by the Ethics Committee of the Institution and informed consent was obtained from all subjects. Data were analyzed with SPSS software package version 17.0 (SPSS Inc., Chicago, IL) and as the data showed significant departures from normality even after log transformation, comparisons among the groups were done by the two-tailed Mann-Whitney U-test. The level of significance was set at p ≤ 0.05.
This work was supported by Fundação de Amparo a Pesquisa de Minas Gerais (FAPEMIG) and Conselho Nacional de Desenvolvimento Científico e Tecnolológico (CNPq), Brazil.
Dr. Dulciene MM Queiroz is funded under The Sixth Framework Program of the European Union, Project CONTENT (INCO-CT-2006-032136).
- Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter D: International consensus report on the investigation and management of primary immune thrombocytopenia. Blood. 2010, 115: 168-186. 10.1182/blood-2009-06-225565.View ArticlePubMedGoogle Scholar
- Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kühne T, Ruggeri M, George JN: Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report form an international working group. Blood. 2009, 113: 2386-2393. 10.1182/blood-2008-07-162503.View ArticlePubMedGoogle Scholar
- Stasi R, Amadori S, Osborn J, Newland AC, Provan D: Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia. Plos Medicine. 2006, 3: 388-394.Google Scholar
- Neunert C, Lim W, Crowther M, Cohen A, Solberg L, Crowther MA: The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011, 117: 4190-4207. 10.1182/blood-2010-08-302984.View ArticlePubMedGoogle Scholar
- Grace RF, Long M, Kalish LA, Neufeld EJ: Applicability of 2009 international consensus terminology and criteria for immune thrombocytopenia to a clinical pediatric population. Pediatr Blood Cancer. 2012, 58: 216-220. 10.1002/pbc.23112.PubMed CentralView ArticlePubMedGoogle Scholar
- Rocha AMC, Souza C, Rocha GA, Melo FF, Clementino NCD, Marino MCA, Bozzi A, Silva ML, Martins-Filho OA, Queiroz DMM: The levels of IL-17A and of the cytokines involved in the Th17 cell commitment are increased in patients with chronic Immune Thrombocytopenia. Haematologica. 2011, 96: 1560-1564. 10.3324/haematol.2011.046417.PubMed CentralView ArticlePubMedGoogle Scholar
- Rocha AMC, Souza C, Rocha GA, Melo FF, Saraiva ISB, Clementino NCD, Marino MCA, Queiroz DMM: IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia. Br J Haematol. 2010, 150: 679-684. 10.1111/j.1365-2141.2010.08318.x.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.