Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40

Lymphangiogenesis in Crohn’s disease: an immunohistochemical study using monoclonal antibody D2-40
F. Pedica1 , C. Ligorio1, P. Tonelli2, S. Bartolini3 and P. Baccarini1
(1)
Section of Pathology, Bellaria Hospital, University of Bologna, Via Altura 3, 40139 Bologna, Italy
(2)
General Surgery 1, Department of Medicine and General Surgery, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
(3)

Unity of Oncology, Bellaria Hospital, Bologna, Italy
Received: 17 September 2007 Revised: 24 October 2007 Accepted: 26 October 2007 Published online: 27 November 2007

Abstract

Crohn’s disease (CD) is a chronic inflammatory bowel disorder of unknown etiology. An involvement of the intestinal lymphatic system has been suggested. Recently, monoclonal antibodies have become available to distinguish lymphatic vessels from blood vessels. The aim of the study was to examine the distribution of lymphatic vessels in ileal and colic walls of patients affected by CD and compare it with healthy controls and other inflammatory bowel diseases. Twenty-eight cases of CD, 13 cases of other inflammatory bowel diseases, and 10 normal ileal and colic walls were studied. Immunohistochemical staining was performed using the monoclonal antibody D2-40. Quantification of lymphatic vessels was performed by identifying four fields with high density of lymphatics and then counting the number of lymphatic vessels at high resolution. Lymphatic diameter was also evaluated by using an ocular micrometer. Lymphatic vessels showed the highest density in CD specimens. The median number of lymphatics was significantly higher both in ileal and colic samples of CD than the other inflammatory diseases as well as normal controls. Moreover, in patients with CD, diffuse lymphangiectasia was also observed. The present data suggest that lymphangiogenesis and lymphangiectasia probably play a role in the pathogenesis of CD.

Springer Link

Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss.

Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss.

J Gastroenterol Hepatol. 2007 Nov 14

Hokari R, Kitagawa N, Watanabe C, Komoto S, Kurihara C, Okada Y, Kawaguchi A, Nagao S, Hibi T, Miura S.Department of Internal Medicine, National Defense Medical College, Saitama, Japan.

Background and Aim: Vascular endothelial growth factor receptor 3 (VEGFR3) and LYVE-1 are specifically expressed in the endothelium of the lymphatic systems. VEGF-C, D, FOXC2, Prox 1, and SOX18 are known to play central roles in lymphatic development. We investigated the expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa of idiopathic intestinal lymphangiectasia.

Methods: Biopsy samples were obtained from duodenal biopsies in patients with intestinal lymphangiectasia complicated with protein-losing from white spot lesions in which lymphangiectasia was histologically confirmed. Immunohistochemical analysis for VEGFR3 and LYVE-1 was performed. mRNA expression of VEGF-C, VEGF-D, VEGFR3, and transcription factors was determined by the quantitative reverse transcription-polymerase chain reaction method.

Results: In the control mucosa, VEGFR3 was weakly expressed on the central lymphatic vessels in the lamina propria and LYVE-1 was expressed mainly on the lymphatic vessels in the submucosa. In intestinal lymphangiectasia, VEGFR3 and LYVE-1 expression levels were increased on the mucosal surface corresponding to widely dilated lymphatic vessels, while they were decreased in the deeper mucosa. mRNA expression study showed a significant increase in the expression level of VEGFR3 in lymphangiectasia, but the expression of VEGF-C and -D mRNA was significantly suppressed compared with that in controls despite the presence of lymphangiectasia. The mRNA expression levels of FOXC2 and SOX18 were also decreased, whereas Prox 1 was not altered.

Conclusions: There is an altered expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa in these patients.

PMID: 18005011 [PubMed - as supplied by publisher]

Osteomalacia in a patient with primary intestinal lymphangiectasis (Waldmann's disease).

Osteomalacia in a patient with primary intestinal lymphangiectasis (Waldmann's disease).

Joint Bone Spine. 2007 Aug 29
Sahli H, Ben Mbarek R, Elleuch M, Azzouz D, Meddeb N, Chéour E, Azzouz MM, Sellami S.
Rheumatology Department, La Rabta Hospital, 1007 Tunis, Tunisia.

Keywords: Waldmann's disease; Primary intestinal lymphangiectasis; Intestinal malabsorption; Osteomalacia; Vitamin D

Primary intestinal lymphangiectasis (PIL), also known as Waldmann's disease, is a rare protein-losing enteropathy characterized by abnormal enlargement of the lymphatic ducts in the bowel wall. The symptoms usually start in early infancy. We report a case of osteomalacia in a 63-year-old patient with delayed-onset of PIL, for which she was on dietary treatment. She presented with a 3-year history of mechanical pain in the back and pelvis. Mild ascites and edema with functional impairment of the lower limbs were noted. The neurological evaluation was normal. Blood tests showed hypocalcemia, hypophosphatemia, alkaline phosphatase elevation, and evidence of intestinal malabsorption. Radiographs of the pelvis disclosed a fracture, Looser's zones in the iliopubic rami and left femoral neck, and a washed-out appearance of the vertebras. Dual-energy X-ray absorptiometry showed bone loss with T-score values of -1.2SD at the lumbar spine and -2.5SD at the femoral necks. A diagnosis of osteomalacia related to vitamin D deficiency was given. Serum 25-OH-vitamin D was 18.2ng/ml (normal, 20-40ng/ml) and serum parathyroid hormone was 620pg/ml (normal, 15-65pg/ml), suggesting secondary hyperparathyroidism. Intramuscular vitamin D was given, together with oral calcium and an adequate diet. At follow-up 8 months later, small improvements were noted in the symptoms and absorptiometry findings.

Elsevier

Edema and protein-losing enteropathy (lymphangiectasia) complicating chronic constrictive pericarditis associated with an ascending aortic aneurysm

Edema and protein-losing enteropathy complicating chronic constrictive pericarditis associated with an ascending aortic aneurysm

**Here is an interesting abstract showing how swelling (ab edema) from pericarditis will trigger protein losing enteropathy (dilation of intestinal lymphatics/protein lose)**

Presse Med. 2007 Nov 5
Article in French]

Lesaffre F, Sandras R, Saade YA, Duval S, Metz D.Département de cardiologie et pathologies vasculaires, CHU de Reims, Hôpital Robert Debré, Avenue du Général Koenig, F-51100 Reims, France.

INTRODUCTION: Chronic constrictive pericarditis is suspected on clinical and echocardiographic grounds. Its treatment is surgical.

CASE: We report here the case of a 45-year-old man, admitted for edema characteristic of lymphatic obstruction. Examination revealed ascending aorta ectasia, associated with chronic constrictive pericarditis. Measurement of alpha-1 antitrypsin clearance confirmed protein-losing enteropathy. Total recovery followed pericardectomy and aneurysm resection.

DISCUSSION: The clinical edema in this case was due to several phenomena: protein-losing enteropathy from a functional lymphatic overload, induced by chronic constrictive pericarditis and by compression of the right atrium and vena cava by an aortic aneurysm. The hypoalbuminemia induced by protein loss may also magnify edema. An association between chronic constrictive pericarditis and ascending aortic aneurysm is uncommon. No cause for this association was found.

PMID: 17988828 [PubMed - as supplied by publisher]