Pneumococcus-induced T-antigen activation in hemolytic uremic syndrome and anemia

Abstract

The hemolytic uremic syndrome (HUS) is most commonly associated with Escherichia coli, but has been associated with other infections such as Streptococcus pneumoniae. Pneumococcus-induced HUS carries an increased risk of mortality and renal morbidity compared with E. coli-induced HUS. The pneumococcal organism produces an enzyme, which can expose an antigen (T-antigen) present on erythrocytes, platelets, and glomeruli. Antibodies to the T-antigen, normally found in human serum, bind the exposed T-antigen, and the resultant antigen-antibody reaction (T-activation) can lead to HUS and anemia. Clinicians need to be aware to request specific testing when pneumococcus-induced HUS/anemia is suspected, as current blood banking techniques do not routinely test for the presence of the T-antigen. Once this association is documented, washing all blood products and avoiding plasma products, if possible, is recommended. Plasmapheresis can be considered for the more critically ill patient. The incidence of pneumococcus-induced HUS may be increasing. We report six cases of pneumococcus-induced HUS/anemia presenting at our hospital.

Streptococcus pneumoniae-associated hemolytic uremic syndrome

“…Since 1987, 73 children [14,16,18,19,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] with pneumococcal HUS have been reported in the English language literature. Of these, 12.3% (9/73) died; 10.1% (7/69) progressed to ESRF; and 16% (11/69) survived, with chronic kidney disease or hypertension.…”

“…Of these, 12.3% (9/73) died; 10.1% (7/69) progressed to ESRF; and 16% (11/69) survived, with chronic kidney disease or hypertension. Detailed clinical [33] and follow-up data [34] were unavailable for four patients. The improved mortality rate in the past 20 years may have been the result of the advances in critical care medicine as opposed to changes in disease virulence [31].…”

“…They also have longer periods of oligo-anuria, more frequent need for acute dialysis (75% vs 59%), longer hospital stays (33 days vs 16 days), more red blood cell and platelet transfusions, and a longer duration of thrombocytopenia [31]. In our review of the 73 patients reported from 1987 to 2007 [14,16,18,19,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] 10.1% developed endstage renal failure (ESRF) and 12.3% died in the acute phase. These rates are two-to-three-times higher than those of STEC HUS [43,44,45].…”

“…There is no evidence that plasmapheresis is of value. Several authors have attributed the recent decrease in mortality rate to earlier recognition and a more conservative approach to transfusion with washed blood products [25,33]. It remains to be seen whether the routine administration of the seven-valent pneumococcal vaccine to infants has effectively decreased the incidence of pneumococcal HUS.…”

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

“…Streptococcus Pneumoniae produces a circulating neuraminidase that removes N-acetylneuraminic acid from cell surfaces. As a consequence, the normally circulating T-antigen antibodies react with the newly exposed T-antigen on red blood cells, platelets and endothelial cells, thus causing hemolytic anemia, thrombocytopenia and micro vascular injury [42] .…”