Diagnosis of amyloidosis and differentiation from chronic, idiopathic enterocolitis in rhesus (Macaca mulatta) and pig-tailed (M. nemestrina) macaques

Abstract

Amyloidosis is a progressive and ultimately fatal disease in which amyloid, an insoluble fibrillar protein, is deposited inappropriately in multiple organs, eventually leading to organ dysfunction. Although this condition commonly affects macaques, there is currently no reliable method of early diagnosis. Changes in clinical pathology parameters have been associated with amyloidosis but occur in late stages of disease, are nonspecific, and resemble those seen in chronic, idiopathic enterocolitis. A review of animal records revealed that amyloidosis was almost always diagnosed postmortem, with prevalences of 15% and 25% in our rhesus and pig-tailed macaque colonies, respectively. As a noninvasive, high-throughput diagnostic approach to improve antemortem diagnosis of amyloidosis in macaques, we evaluated serum amyloid A (SAA), an acute-phase protein and the precursor to amyloid. Using necropsy records and ELISA analysis of banked serum, we found that SAA is significantly elevated in both rhesus and pig-tailed macaques with amyloid compared with those with chronic enterocolitis and healthy controls. At necropsy, 92% of rhesus and 83% of pig-tailed had amyloid deposition in either the intestines or liver. Minimally invasive biopsy techniques including endoscopy of the small intestine, mucosal biopsy of the colon, and ultrasound-guided trucut biopsy of the liver were used to differentiate macaques in our colonies with similar clinical presentations as either having amyloidosis or chronic, idiopathic enterocolitis. Our data suggest that SAA can serve as an effective noninvasive screening tool for amyloidosis and that minimally invasive biopsies can be used to confirm this diagnosis.

Figure 1.

Histopathology of intestinal mucosal pinch biopsies of (A) small intestine with chronic, idiopathic enterocolitis, (B) small intestine with amyloidosis, (C) colon with chronic, idiopathic entercolitis, and (D) colon with amyloidosis. Amyloid protein is homogenous, amorphous, eosinophilic, and indicated by black arrows. Hematoxylin and eosin stain; bar, 20 µm.

Figure 2.

Histopathology of trucut liver biopsy from (A) normal liver tissue from a macaque diagnosed with chronic, idiopathic enterocolitis and (B) liver tissue from a macaque with extensive amyloidosis and sparse remaining hepatocytes. Amyloid protein is homogenous, amorphous, and eosinophilic. Hematoxylin and eosin stain; bar, 20 µm.

Figure 3.

ELISA results of serum amyloid A (SAA) serum concentration compared with diagnosis at necropsy for (A) rhesus and (B) pig-tailed macaques; bars represent median values. Serum amyloid A varied significantly by disease status in both rhesus (Kruskal–Wallis, P = 0.0015, n = 24) and pig-tailed macaques (Kruskal–Wallis, P = 0.0014, n = 31).