Autoimmune enteropathy and nephropathy with circulating anti-epithelial cell antibodies Richard B, Colletti, MD, Ann P. Guillot, MD, Seymour Rosen, MD, Atul K. Bhan, MD, C. D a m o n Hobson, Jr., A. Bernard Collins, G a r y J. Russell, MD, a n d Harland S. Winter, MD From the Combined Program in Gastroenterology and Nutrition, Children's Hospital, and the Departments of Pathology, Beth Israel Hospital and Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and the Department of Pediatrics, University of Vermont College of Medicine, Burlington We describe a child with circulating anti-epithelial cell antibodies, a u t o i m m u n e e n t e r o p a t h y with intestinal villous atrophy, and membranous glomerulonephritis. The patient had persistent diarrhea at 6 months of age, and a small bowel biopsy showed a c t i v e enteritis, villous atrophy, and crypt hyperplasia. When the patient was, 10 months of age, nephrotic syndrome d e v e l o p e d b e c a u s e of membranous glomerulonephritis. Results of tests for circulating immune complexes were negative. Indirect immunofluorescence studies r e v e a l e d a circulating a n t i b o d y d i r e c t e d against renal epithelial cells. Circulating antibodies directed against normal small intestine epithelial cells were also d e t e c t e d by the i m m u n o p e r o x l d a s e technique. Western blot and immunoprecipitation identified a 55-kd antigen, in both small bowel and kidney, that r e a c t e d with an ant i b o d y in the patient's serum. High-dose prednlsone therapy i n d u c e d a clinical remission, resolution of the small bowel injury, and diminished serum anti-epithelial cell antibodies; after dose reduction, clinical relapse occurred with villous atrophy and r e a p p e a r a n c e of anti-epithelial cell antibodles. When the patient was 45 months of age, persistent diarrhea recurred despite intravenous administration of corticosteroids, cyclosporine, and total parenteral nutrition. Autoantibodies to a 55-kd epithelial cell protein are temporally related to the d e v e l o p m e n t of e n t e r o p a t h y and nephropathy. Study of slmilar patients is n e e d e d to determine the role of such antibodies in this disorder. (J PEDIATR 1991;118:858-64) Features of autoimmune disease, such as circulating tissue autoantibodies or a concurrent extraintestinal disorder thought to be autoimmune, have been seen in some infants with intractable diarrhea. H ~ Two patients have been described in whom villous atrophy was associated with membranous glomerulonephritis and a circulating antibody to small intestinal mucosa. 11, 12 We describe a child with

intestinal villous atrophy and immune-mediated membranous glomerulonephritis who had a circulating anti-epithelial cell antibody directed against an epitope present in both small bowel and kidney. AECA

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CASE REPORT Submitted for publication Oct. 8, 1990; accepted Dec. 12, 1990. Reprint requests: Harland S. Winter, MD, Hunnewell Ground, Gastrointestinal Division, Children's Hospital Medical Center, 300 Longwood Ave., Boston MA 02115. 9/20/27288

858

The patient was healthy until 2 months of age, when diarrhea developed and he failed to thrive while being fed cow milk-based and soy-based infant formula (Fig. 1). His condition improved when he was fed a hydrolyzed-protein formula at 3 months of age. When he was 6 months of age, the results of 30 dermal scratch tests,

Volume 118 Number 6

Autoimmune enteropathy

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Fig. t. Correlation of disease activity and treatment with circulating AECAs. High-dose prednisone treatment resulted in resolution of bloody stools, healing of villous atrophy (VA) to normal villi (NV) on small bowel biopsy (S.B.Bx), resolution of nephrotic syndrome, and reduction in circulating AECAs. Lower-dose prednisone therapy resulted in relapse. At age 45 months, patient had relapse that was resistant to high-dose intravenous therapy with corticosteroids, cyclosporine (Cy), and total parenteral nutrition (TPN). Solid bar denotes daily dose of prednisone; vertical lines denote alternate-day dose of prednisone. C, Cow milk; S, soy formula; H, hydrolyzed protein formula; AA, amino acid formula; +, presence of bloody stools; - , absence of bloody stools; MN, membranous nephropathy. including tests of cow milk and soy antigen, were negative. Two hours after he was fed 180 ml of a soy formula, vomiting, bloody diarrhea, shock, and leukocytosis developed. The urinalysis showed normal values. The patient recovered after 48 hours of supportive care, including a transfusion of packed erythrocytes. On a diet of a hydrolyzed-protein formula, rice cereal, pureed fruits and vegetables, but no dairy products, soy, or gluten, the patient had frequent loose stools, poor linear growth, and eczema. When he was 10 months of age, nephrotic syndrome developed, with ascites, peripheral edema, urinary protein level >3 gin/L, serum albumin level of 19 gm/L, and cholesterol level of 7.9 retool/ L (305 mg/dl). The blood leukocyte count was 17.7 • 109/L and the erythrocyte sedimentation rate 40 ram/hr. The urine specific gravity was 1.020, pH 6, with no leukocytes or erythrocytes but >50 hyaline cases per high-power field. The ratio of urinary protein to creatinine was 22.3 (normal

Autoimmune enteropathy and nephropathy with circulating anti-epithelial cell antibodies.

We describe a child with circulating anti-epithelial cell antibodies, autoimmune enteropathy with intestinal villous atrophy, and membranous glomerulo...
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