Human Pathology (2015) 46, 929–931
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Correspondence Comment on autoimmune myelofibrosis Dear Editor, Vergara-Lluri and colleagues [1] describe the histomorphologic features of autoimmune myelofibrosis (AIMF) and associate it with “… a benign clinical course.” Whether the finding of AIMF per se confers a benign clinical course in an affected patient is not known for lack of systematic studies [2,3]. For example, the clinical relevance of AIMF in patients with systemic lupus erythematosus (a major subset of AIMF) is unclear because of selection bias, lack of or short follow-up, and incomplete clinical data in many reported patients [4]. Prospective studies of bone marrow reticulin content in unselected patients with systemic lupus erythematosus together with clinical and laboratory features are needed to determine the prognostic relevance of AIMF in patients with lupus-associated AIMF. VergaraLluri et al are right in underlining the benign nature of the clinicomorphologic entity of AIMF and to distinguish it from chronic idiopathic myelofibrosis, a myeloproliferative neoplasm.
Prasad R. Koduri, MD The Division of Hematology-Oncology, Mediciti Hospital 5-9-22 Secretariat Rd, Hyderabad, India 500063 E-mail address: [email protected]
http://dx.doi.org/10.1016/j.humpath.2014.11.023
References [1] Vergara-Lluri ME, Piatek CI, Pullarkat V, et al. Autoimmune myelofibrosis: an update on morphologic features in 29 cases and review of the literature. HUM PATHOL 2014;45:2183-91. [2] McCarthy DM. Fibrosis of the bone marrow: content and causes. Br J Haematol 1983;59:1-7. [3] Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 2007;139:351-62. [4] Chalayer E, Ffrench M, Cathebras P. Bone marrow fibrosis as a feature of systemic lupus erythematosus: a case report and literature review. SpringerPlus 2014;3:349-58. 0046-8177/© 2015 Elsevier Inc. All rights reserved.
Helicobacter pylori dupA and smoking are associated with increased levels of interleukin-8 in gastric mucosa in Iraq Dear Editor, We read with interest the paper by Nagashima et al [1] about interleukin (IL)–8 expression in Helicobacter pylori– infected gastric mucosa tissues from patients in Bhutan and the Dominican Republic. The cagA genotype was predominantly of East Asian type in Bhutan versus Western type in the Dominican Republic. They also found that the IL-8 mRNA levels were significantly higher in biopsies from Bhutan compared with those from the Dominican Republic. It was implied that East Asian–type cagA-positive strains in Bhutan play a role in the increased expression of IL-8 mRNA [1]. We studied the gastric mucosa IL-8 levels in relation to virulence factors (cagA, vacA, and dupA), smoking, and sex in biopsies taken from 81 H pylori–infected Iraqi patients with nonulcerative disease. It was found that 61.7% of our strains were cagA positive with Western type. It was also found that the IL-8 levels in gastric mucosa infected with cagA-positive H pylori were significantly higher than those in gastric mucosa infected with cagA-negative strains (mean ± SD, 36.3 ± 18 versus 28.3 ± 12; P = .001; Fig. A). No significant association was found between vacA s1 versus vacA s2 or vacA m1 versus vacA m2 regions and IL-8 levels (Fig. C and D). Regarding dupA, we classified our samples into 2 groups: (1) mucosa infected with clustered full-length dupA and (2) mucosa infected with truncated, missing dupA or missing vir genes. In agreement with previous reports [2–4], it was found that the levels of IL-8 were significantly higher in mucosa infected with full-length clustered dupA (36.6 ± 16.6 versus 29 ± 10.3; P = .0001; Fig. B). In addition, the effect of sex and smoking upon the gastric mucosal IL-8 levels was studied. It was found that the IL-8 levels in gastric mucosa sample taken from smokers were significantly higher than those in gastric mucosa of non-smokers (57.3 ± 15 versus 28.3 ± 9.8; P = .0001; Fig. E). No association was found between IL-8 levels and sex (Fig. F). Hence, cagA, full-length clustered dupA, and smoking were associated with increased levels of IL-8 in gastric mucosa. However, multivariate stepwise regression analysis
930
Correspondence
revealed that only infection with full-length clustered dupA-type strain (odds ratio, 1.12; 95% confidence interval, 1.1-1.16) and smoking (odds ratio, 1.14; 95% confidence interval, 1.08-1.2) were independently associated with increased IL-8 levels. In light of these results, it is suggested that other virulence factors, such as dupA, should also be studied in both populations of Bhutan and the Dominican Republic; and this would give better insight into the virulence determinants predisposing to high IL-8 levels. In addition, it was also previously suggested that isolating the influence of a single H pylori virulence factor is extremely difficult and that virulence factors may interact in one way or another in the disease development process [5]. Therefore, results of the association of a single virulence factor with cytokine secretions should be carefully interpreted. Furthermore, it was found that the IL-8 levels in gastric mucosa samples taken from smokers were significantly higher than those of nonsmokers. Therefore, matching for smoking and other environmental factors is suggested in any study comparing gastric mucosal IL-8 levels. Finally, the difference in the samples’ mean age used in the study by Nagashima et al [1] (mean age was 38.5 years for Bhutan versus 47 years for Dominican Republic) and the difference in the genetic makeup of these 2 populations may also play a role in the difference in IL-8 levels.
A
P = .001
B
D
P = NS
E
Nawfal R. Hussein, MD, PhD Department of Internal Medicine School of Medicine Faculty of Medical Sciences Duhok, Kurdistan Region, 8-1014 AM, Iraq E-mail address: [email protected] Ibrahim E. Tuncel, MSc Fatih University, Faculty of Science Department of Biology, Istanbul, Turkey http://dx.doi.org/10.1016/j.humpath.2015.01.021
References [1] Nagashima H, Iwatani S, Cruz M, et al. Differences in interleukin 8 expression in Helicobacter pylori–infected gastric mucosa tissues from patients in Bhutan and the Dominican Republic. HUM PATHOL 2015;46: 129-36. [2] Hussein NR, Abdullah SM, Salih AM, Assafi MA. dupA1 is associated with duodenal ulcer and high interleukin-8 secretion from the gastric mucosa. Infect Immun 2012;80:2971-2. [3] Jung SW, Sugimoto M, Shiota S, Graham DY, Yamaoka Y. The intact dupA cluster is a more reliable Helicobacter pylori virulence marker than dupA alone. Infect Immun 2012;80:381-7. [4] Lu H, Hsu P-I, Graham DY, Yamaoka Y. Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology 2005;128:833-48. [5] Atherton J. The pathogenesis of H pylori–induced gastro-duodenal diseases. Annu Rev Pathol 2006;1:63-96.
P = .0001
P = .0001
C
P = NS
F
P = NS
Fig. Mean levels of IL-8 secretion from gastric mucosa of H pylori–infected Iraqi samples. Significant differences were found between samples infected with H pylori carrying cagA-positive (50 samples) versus cagA-negative (31 samples) genotype (A); full-length clustered dupA (23 samples) versus dupA-negative, truncated dupA, or missing vir genes (58 samples) (B); and smokers (33 samples) versus nonsmokers (48 samples) (E). Nonsignificant (NS) differences were found between samples infected with H pylori carrying vacA s1 (61 samples) versus vacA s2 (20 samples) (C); vacA m1 (13 samples) versus vacA m2 (68 samples) (D); and H pylori isolated from male (46 samples) versus female (35 samples) patients (F). * Outlier.
www.elsevier.com/locate/humpath
Correspondence Comment on autoimmune myelofibrosis Dear Editor, Vergara-Lluri and colleagues [1] describe the histomorphologic features of autoimmune myelofibrosis (AIMF) and associate it with “… a benign clinical course.” Whether the finding of AIMF per se confers a benign clinical course in an affected patient is not known for lack of systematic studies [2,3]. For example, the clinical relevance of AIMF in patients with systemic lupus erythematosus (a major subset of AIMF) is unclear because of selection bias, lack of or short follow-up, and incomplete clinical data in many reported patients [4]. Prospective studies of bone marrow reticulin content in unselected patients with systemic lupus erythematosus together with clinical and laboratory features are needed to determine the prognostic relevance of AIMF in patients with lupus-associated AIMF. VergaraLluri et al are right in underlining the benign nature of the clinicomorphologic entity of AIMF and to distinguish it from chronic idiopathic myelofibrosis, a myeloproliferative neoplasm.
Prasad R. Koduri, MD The Division of Hematology-Oncology, Mediciti Hospital 5-9-22 Secretariat Rd, Hyderabad, India 500063 E-mail address: [email protected]
http://dx.doi.org/10.1016/j.humpath.2014.11.023
References [1] Vergara-Lluri ME, Piatek CI, Pullarkat V, et al. Autoimmune myelofibrosis: an update on morphologic features in 29 cases and review of the literature. HUM PATHOL 2014;45:2183-91. [2] McCarthy DM. Fibrosis of the bone marrow: content and causes. Br J Haematol 1983;59:1-7. [3] Kuter DJ, Bain B, Mufti G, Bagg A, Hasserjian RP. Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres. Br J Haematol 2007;139:351-62. [4] Chalayer E, Ffrench M, Cathebras P. Bone marrow fibrosis as a feature of systemic lupus erythematosus: a case report and literature review. SpringerPlus 2014;3:349-58. 0046-8177/© 2015 Elsevier Inc. All rights reserved.
Helicobacter pylori dupA and smoking are associated with increased levels of interleukin-8 in gastric mucosa in Iraq Dear Editor, We read with interest the paper by Nagashima et al [1] about interleukin (IL)–8 expression in Helicobacter pylori– infected gastric mucosa tissues from patients in Bhutan and the Dominican Republic. The cagA genotype was predominantly of East Asian type in Bhutan versus Western type in the Dominican Republic. They also found that the IL-8 mRNA levels were significantly higher in biopsies from Bhutan compared with those from the Dominican Republic. It was implied that East Asian–type cagA-positive strains in Bhutan play a role in the increased expression of IL-8 mRNA [1]. We studied the gastric mucosa IL-8 levels in relation to virulence factors (cagA, vacA, and dupA), smoking, and sex in biopsies taken from 81 H pylori–infected Iraqi patients with nonulcerative disease. It was found that 61.7% of our strains were cagA positive with Western type. It was also found that the IL-8 levels in gastric mucosa infected with cagA-positive H pylori were significantly higher than those in gastric mucosa infected with cagA-negative strains (mean ± SD, 36.3 ± 18 versus 28.3 ± 12; P = .001; Fig. A). No significant association was found between vacA s1 versus vacA s2 or vacA m1 versus vacA m2 regions and IL-8 levels (Fig. C and D). Regarding dupA, we classified our samples into 2 groups: (1) mucosa infected with clustered full-length dupA and (2) mucosa infected with truncated, missing dupA or missing vir genes. In agreement with previous reports [2–4], it was found that the levels of IL-8 were significantly higher in mucosa infected with full-length clustered dupA (36.6 ± 16.6 versus 29 ± 10.3; P = .0001; Fig. B). In addition, the effect of sex and smoking upon the gastric mucosal IL-8 levels was studied. It was found that the IL-8 levels in gastric mucosa sample taken from smokers were significantly higher than those in gastric mucosa of non-smokers (57.3 ± 15 versus 28.3 ± 9.8; P = .0001; Fig. E). No association was found between IL-8 levels and sex (Fig. F). Hence, cagA, full-length clustered dupA, and smoking were associated with increased levels of IL-8 in gastric mucosa. However, multivariate stepwise regression analysis
930
Correspondence
revealed that only infection with full-length clustered dupA-type strain (odds ratio, 1.12; 95% confidence interval, 1.1-1.16) and smoking (odds ratio, 1.14; 95% confidence interval, 1.08-1.2) were independently associated with increased IL-8 levels. In light of these results, it is suggested that other virulence factors, such as dupA, should also be studied in both populations of Bhutan and the Dominican Republic; and this would give better insight into the virulence determinants predisposing to high IL-8 levels. In addition, it was also previously suggested that isolating the influence of a single H pylori virulence factor is extremely difficult and that virulence factors may interact in one way or another in the disease development process [5]. Therefore, results of the association of a single virulence factor with cytokine secretions should be carefully interpreted. Furthermore, it was found that the IL-8 levels in gastric mucosa samples taken from smokers were significantly higher than those of nonsmokers. Therefore, matching for smoking and other environmental factors is suggested in any study comparing gastric mucosal IL-8 levels. Finally, the difference in the samples’ mean age used in the study by Nagashima et al [1] (mean age was 38.5 years for Bhutan versus 47 years for Dominican Republic) and the difference in the genetic makeup of these 2 populations may also play a role in the difference in IL-8 levels.
A
P = .001
B
D
P = NS
E
Nawfal R. Hussein, MD, PhD Department of Internal Medicine School of Medicine Faculty of Medical Sciences Duhok, Kurdistan Region, 8-1014 AM, Iraq E-mail address: [email protected] Ibrahim E. Tuncel, MSc Fatih University, Faculty of Science Department of Biology, Istanbul, Turkey http://dx.doi.org/10.1016/j.humpath.2015.01.021
References [1] Nagashima H, Iwatani S, Cruz M, et al. Differences in interleukin 8 expression in Helicobacter pylori–infected gastric mucosa tissues from patients in Bhutan and the Dominican Republic. HUM PATHOL 2015;46: 129-36. [2] Hussein NR, Abdullah SM, Salih AM, Assafi MA. dupA1 is associated with duodenal ulcer and high interleukin-8 secretion from the gastric mucosa. Infect Immun 2012;80:2971-2. [3] Jung SW, Sugimoto M, Shiota S, Graham DY, Yamaoka Y. The intact dupA cluster is a more reliable Helicobacter pylori virulence marker than dupA alone. Infect Immun 2012;80:381-7. [4] Lu H, Hsu P-I, Graham DY, Yamaoka Y. Duodenal ulcer promoting gene of Helicobacter pylori. Gastroenterology 2005;128:833-48. [5] Atherton J. The pathogenesis of H pylori–induced gastro-duodenal diseases. Annu Rev Pathol 2006;1:63-96.
P = .0001
P = .0001
C
P = NS
F
P = NS
Fig. Mean levels of IL-8 secretion from gastric mucosa of H pylori–infected Iraqi samples. Significant differences were found between samples infected with H pylori carrying cagA-positive (50 samples) versus cagA-negative (31 samples) genotype (A); full-length clustered dupA (23 samples) versus dupA-negative, truncated dupA, or missing vir genes (58 samples) (B); and smokers (33 samples) versus nonsmokers (48 samples) (E). Nonsignificant (NS) differences were found between samples infected with H pylori carrying vacA s1 (61 samples) versus vacA s2 (20 samples) (C); vacA m1 (13 samples) versus vacA m2 (68 samples) (D); and H pylori isolated from male (46 samples) versus female (35 samples) patients (F). * Outlier.
