Effects of sporadic transthyretin amyloidosis frequently on the gallbladder and the correlation between amyloid deposition in the gallbladder and heart

The aim of the study is to evaluate the clinicopathological features of cholecystic ATTR deposition in patients with cardiac involvement, investigate the correlation of amyloid deposition severity in the gallbladder and the heart, and compare its prevalence in the gallbladder and other organs. Fifty patients with sporadic ATTR amyloidosis were identified. Of these, we evaluated 15 patients who underwent gallbladder sampling accurately. Among 10 patients (67%) with cholecystic deposition, six exhibited detectable deposition in the hematoxylin and eosin-stained specimens, and all of them displayed obstructive vascular deposition (VD). The severity of gall bladder VD was statistically correlated with that of cardiac VD and atrial interstitial deposition (ID). Additionally, all patients exhibiting cholecystic ID displayed severe ventricular and atrial IDs. In visceral organs excluding the heart, amyloid deposition was commonly observed in the lungs (93%), followed by the gastrointestinal tract (47%‒80%), liver (60%), and periosteal tissues (53%). The involvement of gallbladder was prevalent and comparable to that of the gastrointestinal tract. Moreover, the severity of cholecystic deposition was correlated with that of cardiac deposition. Therefore, pathologists should be aware that sporadic ATTR amyloidosis is a common condition and should not be overlooked.

Improvement of Renal Function by Long-Term Sustained Eculizumab Treatment in a Patient with Paroxysmal Nocturnal Hemoglobinuria

Chronic kidney disease (CKD) is one of the major manifestations of paroxysmal nocturnal hemoglobinuria (PNH). CKD in PNH is induced mainly by intravascular hemolysis of PNH-affected red blood cells (RBC) missing the glycosylphosphatidylinositol-anchored proteins with complement-regulatory activities, CD55 and CD59. CKD develops by heme absorption in the proximal tubules resulting in the interstitial deposition of iron in the kidneys. We administered eculizumab to a patient with PNH, who was one of 29 patients enrolled in the AEGIS clinical trial, an open-label study of eculizumab in Japan. The patient was complicated by stage 3 CKD with impaired estimated glomerular filtration rate (eGFR), at grade G3b, and had obvious proteinuria (2-3+, 1-2 g/day). In a two-year extension to the 12-week AEGIS study, eGFR improved significantly, and the eGFR has since been maintained at grade G2 without proteinuria by sustained eculizumab treatment (>6 years). Renal function improved and maintained by long-term sustained eculizumab treatment, presumably by clearance of iron from the kidney as well as inhibition of the production of anaphylatoxin C5a, even in advanced stages of CKD, is one of the benefits of eculizumab treatment in PNH.

IgM-Mesangial Nephropathy in Callithricids

Spontaneous IgM-mediated mesangioproliferative nephropathy was detected in 91% of tamarins and marmosets over 6 months old. The disease remains silent for long periods but is progressive. It is responsible for, or is at least related to, the cause of death in 20% of animals. Morphological characteristics are those of mesangial hyperplasia accompanied by subacute to chronic interstitial inflammation. The immunopathological demonstration of early accumulation of IgM within the mesangial cells and matrix, followed by interstitial deposition of C3, suggests that the lesion is mediated by immunological mechanisms.