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 wereH 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, forH 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.

Table 1.

Comparison of HLA-DRB1/-DQB1 frequencies of ITP patients and controls and relationship with Helicobacter pyloriinfection

HLA class II alleles ITP patients (%), n = 39 Controls (%), n = 150 P* ITP patients (%), n = 39  
H pylori+, n = 24 H pylori, n = 15 P 
DRB1       
*01 8  (20.5) 32  (21.3) NS 5  (20.8) 3  (20.0) NS  
*15 7  (17.9) 30  (20.0) NS 3  (12.5) 4  (26.7) NS  
*16 5  (12.8) 12  (10.2) NS 2  (8.3) 3  (20.0) NS 
*03 10  (25.6) 28  (18.6) NS 3  (12.5) 7  (46.7) .01  
*04 6  (15.4) 21  (14.0) NS 4  (16.7) 2  (13.3) NS 
*11 12  (30.8) 68  (45.3) .04 10  (41.7) 2  (13.3) .03  
*12 4  (2.6) NS — 
*13 6  (15.4) 28  (18.6) NS 4  (16.7) 2  (13.3) NS  
*14 6  (15.4) 15  (10.0) NS 6  (25.0) .02 
*07 9  (23.1) 26  (17.3) NS 6  (25.0) 3  (20.0) NS  
*08 3  (7.7) 6  (4.0) NS 2  (8.3) 1  (6.7) NS 
*0910 2  (1.3) NS — 
*1001 6  (4.0) NS — 
DQB1       
*02 17  (43.6) 48  (32.0) NS 9  (37.5) 8  (33.3) NS 
*03 17  (43.6) 94  (62.6) .03 14  (58.3) 3  (20.0) .02  
*04 3  (7.7) 7  (4.6) NS 2  (8.3) 1  (6.7) NS 
*05 17  (43.6) 66  (44.0) NS 11  (45.8) 6  (40.0) NS  
*06 10  (25.6) 50  (33.3) NS 5  (20.8) 5  (33.3) NS 
HLA class II alleles ITP patients (%), n = 39 Controls (%), n = 150 P* ITP patients (%), n = 39  
H pylori+, n = 24 H pylori, n = 15 P 
DRB1       
*01 8  (20.5) 32  (21.3) NS 5  (20.8) 3  (20.0) NS  
*15 7  (17.9) 30  (20.0) NS 3  (12.5) 4  (26.7) NS  
*16 5  (12.8) 12  (10.2) NS 2  (8.3) 3  (20.0) NS 
*03 10  (25.6) 28  (18.6) NS 3  (12.5) 7  (46.7) .01  
*04 6  (15.4) 21  (14.0) NS 4  (16.7) 2  (13.3) NS 
*11 12  (30.8) 68  (45.3) .04 10  (41.7) 2  (13.3) .03  
*12 4  (2.6) NS — 
*13 6  (15.4) 28  (18.6) NS 4  (16.7) 2  (13.3) NS  
*14 6  (15.4) 15  (10.0) NS 6  (25.0) .02 
*07 9  (23.1) 26  (17.3) NS 6  (25.0) 3  (20.0) NS  
*08 3  (7.7) 6  (4.0) NS 2  (8.3) 1  (6.7) NS 
*0910 2  (1.3) NS — 
*1001 6  (4.0) NS — 
DQB1       
*02 17  (43.6) 48  (32.0) NS 9  (37.5) 8  (33.3) NS 
*03 17  (43.6) 94  (62.6) .03 14  (58.3) 3  (20.0) .02  
*04 3  (7.7) 7  (4.6) NS 2  (8.3) 1  (6.7) NS 
*05 17  (43.6) 66  (44.0) NS 11  (45.8) 6  (40.0) NS  
*06 10  (25.6) 50  (33.3) NS 5  (20.8) 5  (33.3) NS 

The χ2 method with Yates correction and Fisher exact test were used for data analysis.

NS indicates not significant.

*

ITP patients versus healthy controls.

H pylori–positive patients versus H pylori–negative patients.

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.

Idiopathic thrombocytopenic purpura, Helicobacter pyloriinfection, and the HLA system

The 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 112H pylori–infected patients out of a total of 193 ITP patients studied so far.1-1 Thus, by including the 24H 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 ofH 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,1-2 whereas that allele has been found at high frequency in French HCV-positive patients with mixed cryoglobulinemia and vasculitis.1-3 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.1-4 In aplastic anemia, HLA-DR2 has been found at increased frequency, particularly in patients with associated paroxysmal nocturnal hemoglobinuria.1-5 The findings about H pyloriinfection 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.1-6 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.1-7,1-8 Similarly, other different alleles were found at high or low frequency in Caucasian, Chinese, Spanish, Greek, and Japanese patients infected with H pylori.1-9-1-13 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.

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