Enterocyte apoptosis and proliferation are increased in microvillous inclusion disease (Familial microvillous atrophy)

• Published in: Human pathology 2000-11, Vol.31 (11), p.1404-1410
• Main Authors: Groisman, Gabriel M., Sabo, Edmond, Meir, Alona, Polak-Charcon, Sylvie
• Format: Article
• Language: English
• Subjects: Apoptosis; apoptotic index; Atrophy; Biological and medical sciences; Diarrhea, Infantile - genetics; Diarrhea, Infantile - metabolism; Diarrhea, Infantile - pathology; DNA - analysis; Enterocytes - metabolism; Enterocytes - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; In Situ Nick-End Labeling; Infant; Infant, Newborn; Intestine, Small - metabolism; Intestine, Small - pathology; Ki-67 Antigen - metabolism; Male; Medical sciences; Microvilli - metabolism; Microvilli - pathology; microvillous inclusion disease; Mitotic Index; Other diseases. Semiology; proliferation; proliferation index; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; terminal uridine deoxynucleotidyl nick end labeling; total parenteral nutrition; TPN; TUNUL
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/S0046-8177(00)80011-8

Microvillous inclusion disease (MID) is characterized by diffuse villous atrophy without inflammatory changes. While increased apoptosis has been related to mucosal flattening in celiac disease, the role of apoptosis in the pathogenesis of MID is unknown. The aim of this study was to assess the rates of apoptosis and cell proliferation in MID and to compare them with those of normal controls and celiac disease. Small intestinal biopsies from 5 infants with MID, 10 children with normal villous architecture, and 10 children with untreated celiac disease were stained with the terminal uridine deoxynucleotidyl nick end labeling (TUNEL) method to assess apoptotic activity, and with Ki-67 immunchistochemistry to assess cellular proliferation. TUNEL and Ki-67 positive enterocytes were counted in a minimum of 20 well oriented half crypts per section. The percentage of apoptotic cells per crypt (apoptotic index) in normal, MID, and celiac biopsies was 0.03 ± 0.01%, 0.08 ± 0.08%, and 0.16 ± 0.3%, respectively. Significant differences were found between normal and MID, and between normal and celiac cases. The percentage of Ki-67 positive cells per crypt (proliferation index) in normal, MID, and celiac cases was 14 ± 2.5%, 28 ± 9.2%, and 56 ± 14%. Significant differences were found between the 3 groups. In conclusion, (1) enterocyte apoptosis and proliferation are increased in MID; (2) apoptosis appears to be an important factor of cell loss and may be, at least in part, responsible for villous atrophy in MID; and (3) crypts in MID are hyperplastic and not hypoplastic.