Significant Intrapulmonary Schistosoma Egg Antigens are not Present in Schistosomiasis‐Associated Pulmonary Hypertension

Abstract

Schistosomiasis-associated pulmonary arterial hypertension (PAH) is one of the most common causes of pulmonary hypertension worldwide. A potential contributing mechanism to the pathogenesis of this disease is a localized immune reaction to retained and persistent parasite-derived antigens. We sought to identify Schistosoma-derived egg antigens present in the lungs of individuals who died of the disease. We obtained 18 lung samples collected at autopsy from individuals who died of schistosomiasis-associated PAH in Brazil. A rabbit polyclonal antibody was created to known Schistosoma mansoni-soluble egg antigen (SEA). Histologic assessment and immunostaining of the human tissue was performed, along with immunostaining and immunoblotting of lung tissue from mice experimentally infected with S. mansoni. All 18 lung samples had evidence of pulmonary vascular remodeling with plexiform lesions and arterial medial thickening, but no visible eggs were seen. The anti-SEA antibody detected S. mansoni egg antigens in visible eggs in mouse lung and human intestine specimens, but did not identify a significant amount of egg antigen in the human lung specimens. In mouse granulomas containing degraded eggs, we observed colocalization of egg antigens and macrophage lysosomes. In conclusion, there is unlikely to be a significant amount of persistent parasite-derived antigens within the lungs of individuals who die of schistosomiasis-associated PAH. This suggests that retained and persistent parasite proteins are not contributing to a localized immune response in the pathogenesis of this disease.

The Causal Role of IL-4 and IL-13 inSchistosoma mansoniPulmonary Hypertension

“…Of note, Schistosoma-PAH patients would need to be first treated with antihelmenthic therapy before such biologic inhibitors, to eradicate any active infection, because antiinflammatory therapy suppresses the host-parasite response. Such an approach is warranted, however, because modern series report patients are dying of this disease despite antihelminthic treatment and in the absence of active infection (19,34).…”

“…We have developed a robust and reproducible mouse model of Schistosoma-induced PH using intraperitoneal sensitization followed by intravenous challenge with S. mansoni eggs (8,10,11,19). This model bypasses potentially confounding effects of liver disease and abbreviates the development of PH to 21 days.…”

Schistosomiasis and pulmonary hypertension

“…Ş-PHT'de oluşan lezyonun en ilginç yanı İPAH ile olan benzerliğidir (1). Kronik şistosoma infeksiyonuna bağlı PAH nedeniyle kaybedildiği düşünülen hastaların otopsi çalışmalarında akciğerlerde S. mansoni yumurta ve yumurta antijeni bulunamamıştır (14). İmmünolojik kaskat bir kez başladığında, parazit akciğerden temizlenmiş olsun veya olmasın, PHT'ye yol açan pulmoner vaskülopa-ti gelişebilir.…”

“…Bu durum parazit tedavi edilse, yumurta ve antijenleri eradike edilse bile pulmoner vaskülo-patinin sebat edebileceğini gösterir (15). Daha fazla parazit yumurta yükü daha kötü hastalık ile korele bulunmasına rağmen, ağır PHT için yumurtanın varlığı gerekmemektedir (14,15).…”

“…Şistosomaya bağlı hepatosplenik hastalık sonrasında portal hipertansiyon ve sonuç olarak PHT gelişir. Bu olay damar yatağında granülom veya parazit yumurta embolizasyonu olmaksızın PHT'yi açıklamaktadır (14).…”