Pathology of AA Amyloidosis in Domestic Sheep and Goats

Abstract

We describe the main pathologic changes in small ruminants affected by AA amyloidosis, together with the partial sequence of the protein involved. Twenty-one sheep and one goat were selected for presenting macroscopic kidney lesions compatible with systemic amyloidosis. Available tissue samples were studied by histologic, immunopathologic, and ultrastructural means. Renal lesions were characterized grossly by pale cortical surfaces with scattered, miliary, whitish-yellow foci and on cut cortical surfaces by straight, whitish-yellow striations. Gangrenous pneumonia was observed in 16 out of 21 affected sheep (76.2%), although other chronic inflammations were also observed. Amyloid was detected in all grossly affected kidneys using Congo red staining, lesions being most remarkable in glomeruli, affecting 95.5% of animals studied. Congophilic deposits were also observed in intertubular interstitium (68.2%) and medulla (57.1%). All amyloid-affected animals presented proximal convoluted tubule lesions, mostly characterized by an increase in diameter and by hyaline granular degeneration that were responsible for the macroscopic appearance of the kidney. Histologically, amyloid was also seen in blood vessels, spleen, liver, lymph nodes, gastrointestinal tract, and adrenal glands. All amyloid deposits demonstrated greenish-yellow birefringence with polarized light, and the antisera prepared against goat amyloid extracts specifically reacted with birefringent congophilic deposits of both sheep and goats. Ultrastructurally, these deposits were formed by masses of straight, nonbranching fibrils located predominantly in the basement membranes of glomerular capillaries and in the mesangium. Partial sequence of the protein in sheep and goats indicated a high degree of homology with the previously reported sequence of sheep Serum Amyloid A.

Immunohistochemical distribution of Amyloid Deposits in 25 Cows Diagnosed with Systemic AA Amyloidosis

“…AA amyloidosis characteristically develops in humans and animals as a consequence of a long-standing chronic infectious or inflammatory process [12]. It has been reported that gangrenous pneumonia seems to be relatively high in AA amyloidosis of adult sheep [12]. The cows we examined tended to have chronic mastitis and pneumonia as concurrent inflammatory lesions.…”

“…Amyloidosis is a general term describing a group of diseases characterized by extracellular deposition of amyloid, in the form of ultrastructurally similar but biochemically distinct proteins, in various organs and tissues [3,12]. In animals, at least eight different amyloid precursors have been described.…”

“…When the blood concentration of SAA is increased, typically as a result of chronic inflammation, certain isoforms of SAA are partially cleaved into fragments that have an increased propensity to form fibrillar aggregates (amyloid). This sequence of reactions results in the systemic deposit of amyloid, mainly in the kidney, liver, spleen and intestine [7,12]. Recently, it has been reported that AA amyloidosis in mice is induced by the administration of amyloid enhancing factor (AEF), including AA amyloid fibrils, when there is concurrent inflammatory stimulation [4,11].…”

“…Recently, it has been reported that AA amyloidosis in mice is induced by the administration of amyloid enhancing factor (AEF), including AA amyloid fibrils, when there is concurrent inflammatory stimulation [4,11]. In cattle, there have been many reported cases of amyloidosis [5,6,8,[12][13][14][15]. However, the distribution of amyloid deposition has not been described across the entire body.…”

“…It seemed to be related to the onset of systemic amyloidosis and aging, but the distribution and degree of the amyloid deposits were not correlated with aging. AA amyloidosis characteristically develops in humans and animals as a consequence of a long-standing chronic infectious or inflammatory process [12]. It has been reported that gangrenous pneumonia seems to be relatively high in AA amyloidosis of adult sheep [12].…”