Satoshi Ueda

C4d and C4bp deposition along the glomerular capillarywalls in a patient with preeclampsia

Complement (C) 4d and cofactor C4b binding protein (C4bp) are detected in the glomerular capillary walls of a patient with preeclampsia. A 32-year-old nullipara had proteinuria of 1.2 g/d and edema at the 33rd week of pregnancy. Gradually the urinary protein excretion increased, reaching 5.1 g/d at the 37th week. The patient also showed hypertension at this stage. After normal mature delivery, the level of the urinary protein excretion remained at 3 to 4 g/d. Renal biopsy performed by means of light and electron microscopy, 15 days after delivery, showed almost normal glomeruli and modest subendothelial widening. Immunohistochemistry indicated that immunoglobulin (Ig) A, IgG, C1q, C3c, and C4c were not deposited in the glomeruli, whereas weakly positive IgM and fibrin-related antigen (FRA) were observed. Conversely, C4d, C3d, and C4bp were strongly deposited. Protein S (PS) also was observed, with a similar distribution pattern to that of C4bp. Immunoelectron microscopy showed the deposition of C4d along the capillary walls and of C4bp in the subendothelium. These findings suggest that the C4 activation process as well as the regulation process of C system and of the inflammatory coagulation axis by C4bp and PS may play an important role in the pathophysiology of preeclampsia, so-called glomerular capillary endotheliosis (GCE).

A 41-year-old woman with protein S deficiency and diffuse proliferative lupus nephritis: Is protein S deficiency associated with a hyperinflammatory response?

A 41-year-old woman with complete protein S (PS) deficiency who developed diffuse proliferative lupus nephritis is reported. She was referred to our hospital with nephrotic syndrome and thrombocytopenia. Her medical history included colorectostomy and amputation of the extremities because of repeated thrombotic episodes during her teens without any evidence of systemic lupus erythematosus. The diagnosis of PS deficiency was made from the patients clinical course, undetectable serum PS in either the active or inactive form, normal protein C activity, and no evidence of the antiphospholipid syndrome. However, there was no definitive family history. A depressed level of complements and a positive antinuclear acid antibody suggested a diagnosis of systemic lupus erythematosus. The patient had a rapidly progressive course and died of disseminated intravascular coagulation. An autopsy showed generalized thrombotic lesions and diffuse proliferative lupus nephritis on both ordinal light and immunoperoxidase microscopy. Our observations suggest that PS-deficient patients may have a hyperinflammatory response.