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CORRESPONDENCE Recently, Emilia et al1 reported a high
prevalence of Helicobacter pylori infection in patients with
idiopathic thrombocytopenic purpura (ITP) and a significant increase in
platelet count after bacterium eradication. In this study, we analyzed
the correlation between H pylori infection and HLA class II
alleles in 39 ITP patients (median age, 48.9 years; range, 21-82 years;
17 males, 22 females; M/F ratio, 0.8) observed at our department
between December 1998 and April 2002. We compared the frequency of the HLA-DR/-DQ antigens in these patients with that of 150 healthy bone
marrow donors, matched for sex and age (Table 1). The frequency of
HLA-DRB1*11 and -DQB1*03 alleles were significantly lower in ITP
patients than in healthy controls. None of the other alleles (HLA-DRB1*1, *15, *16, *03, *04, *12, *13, *14, *07, *08, *0910, *1001;
and -DQB1*02, *04, *05, *06) was differently expressed in ITP patients
and healthy controls. The 39 patients were then compared for the
presence of H pylori infection: 24 patients were H pylori-positive and 15 patients were H
pylori-negative (Table 1). These 2 groups differed for median age (56.5 years, range, 21-82 years, for
H pylori-positive patients; 41 years, range, 22-70 years,
for H pylori-negative patients;
P = .03), for sex (9 males and 15 females, M/F
ratio, 0.6, for H pylori-positive patients; 8 males and 7 females, M/F ratio, 1.1, for H pylori-negative patients),
and for HLA class II alleles distribution. H
pylori-negative patients showed an HLA-DRB1*03 frequency
significantly higher and a -DRB1*11, *14 and -DQB1*03
frequencies significantly lower than in H
pylori-positive patients. The lower frequencies of HLA-DRB1*11 and of -DQB1*03 alleles observed in our ITP patients seems to be a
typical feature of H pylori-negative cases. No significant differences in any of the class II alleles was observed in H
pylori-positive patients as compared with controls.
So far, there is little evidence of an association between major histocompatibility complex class II and ITP.2-5 A higher prevalence of other class II alleles and ITP patients has been described in some human races,2 although other studies failed to demonstrate a statistically significant association.4,5 By contrast, in our study the HLA class II allele pattern seems to identify 2 groups of ITP patients with a different incidence of H pylori infection and, possibly, with different pathogenetic mechanisms.
Dino Veneri, Michele Gottardi, Elisabetta Guizzardi, Carla Zanuso, Mauro Krampera, and Massimo Franchini
References
1.
Emilia G, Longo G, Luppi M, et al.
Helicobacter pylori eradication can induce platelet recovery in idiopathic thrombocytopenic purpura.
Blood.
2001;97:812-814
2.
Nomura S, Matsuzaki T, Ozaki Y, et al.
Clinical significance of HLA-DRB1*0410 in Japanese patients with idiopathic thrombocytopenic purpura.
Blood.
1998;91:3616-3622
3.
Cines DB, Blanchette VS.
Immune thrombocytopenic purpura.
N Engl J Med.
2002;346:995-1008
4.
Leung AYH, Hawkins BR, Chim CS, Kwong YL, Liang RHS.
Genetic analysis of HLA-typing in Chinese patients with idiopathic thrombocytopenic purpura.
Haematologica.
2001;86:221-222 5. Gaiger A, Neumeister A, Heinzl H, Pabinger I, Panzer S. HLA class-I and -II antigens in chronic idiopathic autoimmune thrombocytopenia. Ann Hematol. 1994;68:299-302[CrossRef][Medline] [Order article via Infotrieve].
Response:Idiopathic thrombocytopenic purpura, Helicobacter pylori infection, and the HLA systemThe interesting letter of Veneri et al gives us the opportunity for some remarks. First of all, the authors confirm the high prevalence of Helicobacter pylori infection in idiopathic thrombocytopenic purpura (ITP) patients. In a recent careful review of the literature, including an update of our case series, we found 112 H pylori-infected patients out of a total of 193 ITP patients studied so far.1 Thus, by including the 24 H pylori infected, out of the 39 ITP patients reported by Veneri et al, the prevalence of H pylori infection in ITP is 58.6%. Of course, this important association between ITP and a bacterium infection may prompt to investigate whether host genetic factors are involved in the pathogenesis of the disease and in susceptibility to infection. With respect to this, the study of human leukocyte antigens (HLAs) seems to be appropriate. Veneri et al found that a low frequency of HLA-DRB1*11 and -DQB1*03 alleles characterizes the ITP patients compared with healthy controls. Moreover, a low frequency of such alleles seems to be typical of H pylori-negative patients. This is a suggestive finding, but we would like to introduce a note of caution. The complexity of HLA system, the variability of H pylori strains, and the yet not well defined pathophysiology of ITP make this type of in vivo investigations very complicated. In particular, in the literature there is a very large amount of reports dealing with possible correlations between diseases with underlying immune mechanisms and HLA system, with a great many alleles that correlate to certain features of the disease, while other alleles do not. For example, the HLA-DRB1*11 allele has been found at low frequency in hepatitis C virus (HCV)-positive Turkish patients,2 whereas that allele has been found at high frequency in French HCV-positive patients with mixed cryoglobulinemia and vasculitis.3 In HIV-positive patients the -DR*11 allele seems to represent a risk factor for the AIDS development and poor prognosis, but some reports have failed to confirm such an association between HLA and the disease.4 In aplastic anemia, HLA-DR2 has been found at increased frequency, particularly in patients with associated paroxysmal nocturnal hemoglobinuria.5 The findings about H pylori infection and HLA are contradictory. Some HLA alleles, like -DQB1*0602, have been found at high frequency in H pylori-positive patients favoring gastric cancer occurrence, whereas -DQB1*0301 seems to be protective against cancer in Taiwanese patients.6 In contrast, other alleles were found to be not associated with H pylori infection and cancer risk in Italian (-DQA1 and -DQB1) and German (-DQA1, -DQB1, and HLA class II) patients, respectively, whereas -DRB1*1501, -DQA1*01021, and -DQB1*0602 seem to be protective against H pylori infection in Japanese patients.7,8 Similarly, other different alleles were found at high or low frequency in Caucasian, Chinese, Spanish, Greek, and Japanese patients infected with H pylori.9-13 Similarly, as reported by Veneri et al, the few studies on ITP and H pylori infection revealed contradictory findings concerning a correlation with HLA alleles. A better reassessment of these data and their possible clinical relevance should await for further rigorous studies on specific HLA alleles on very large series of ITP patients, which could necessarily take into account the racial differences of the population groups tested and also the H pylori-strain differences.
Giovanni Emilia, Mario Luppi, Monica Morselli, Giuseppe Longo, and Giuseppe Torelli
References 1. Emilia G, Luppi M, Morselli M, Potenza L, D'Apollo N, Torelli G. Helicobacter pylori infection and idiopathic thrombocytopenic purpura. Br J Haematol. 2002. In press.
2.
Yenigun A, Durupinar B.
Decreased frequency of the HLA-DRB1*11 allele in patients with chronic hepatitis C virus infection.
J Virol.
2002;76:1787-1789 3. Cacoub P, Renou C, Kerr G, et al. Influence of HLA-DR phenotype on the risk of hepatitis C virus-associated mixed cryoglobulinemia. Arthritis Rheum. 2001;44:2118-2124[CrossRef][Medline] [Order article via Infotrieve]. 4. Al Jabri AA. HLA and in vitro susceptibility to HIV infection. Mol Immunol. 2002;38:959-967[Medline] [Order article via Infotrieve].
5.
Maciejewski JP, Follmann D, Nakamura R, et al.
Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome.
Blood.
2001;98:3513-3519 6. Wu MS, Hsieh RP, Huang SP, et al. Association of HLA-DQB1*0301 and HLA-DQB1*0602 with different subtypes of gastric cancer in Taiwan. Jpn J Cancer Res. 2002;93:404-410[Medline] [Order article via Infotrieve]. 7. Perri F, Piepoli A, Quitadamo M, Quarticelli M, Merla A, Bisceglia M. HLA-DQA1 and -DQB1 genes and Helicobacter pylori infection in Italian patients with gastric adenocarcinoma. Tissue Antigens. 2002;59:55-57[Medline] [Order article via Infotrieve]. 8. Kunstmann E, Hardt C, Treitz H, et al. In the European population HLA-class II genes are not associated with Helicobacter pylori infection. Eur J Gastroenterol Hepatol. 2002;14:49-53[Medline] [Order article via Infotrieve].
9.
Magnusson PKE, Enroth H, Eriksson I, et al.
Gastric cancer and human leukocyte antigen: distinct DQ and DR alleles are associated with development of gastric cancer and infection by Helicobacter pylori.
Cancer Res.
2001;61:2684-2689 10. Santolaria S, Barrios Y, Benito R, Piazuelo E, Quintero E, Lanas A. Helicobacter pylori and immunogenetic factors of the host: relevance of the HLADQA1*0102 and *0301 alleles in peptic ulcer. Gastroenterol Hepatol. 2001;24:117-121[Medline] [Order article via Infotrieve]. 11. Gao C, Li Z, Ding J. Study on the relations between HLA-DRB1 alleles and Helicobacter pylori infection. Zhonghua Liu Xing Bing Xue Za Zhi. 2000;21:417-419[Medline] [Order article via Infotrieve]. 12. Archimandritis A, Sougioultzis S, Foukas PG, Tzivras M, Davaris P, Moutsopoulos HM. Expression of HLA-DR, costimulatory molecules B7-1, B7-2, intercellular adhesion molecule-1 (ICAM-1) and Fas ligand (FasL) on gastric epithelial cells in Helicobacter pylori gastritis; influence of H pylori eradication. Clin Exp Immunol. 2000;119:464-471[CrossRef][Medline] [Order article via Infotrieve]. 13. Yoshitake S, Okada M, Kimura A, Sasazuki T. Contribution of major histocompatibility complex genes to susceptibility and resistance in Helicobacter pylori related diseases. Eur J Gastroenterol Hepatol. 1999;11:875-880[Medline] [Order article via Infotrieve].   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
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