Red cells from ferrochelatase-deficient erythropoietic protoporphyria patients are resistant to growth of malarial parasites.

Many red cell polymorphisms are a result of selective pressure by the malarial parasite. Here, we add another red cell disease to the panoply of erythrocytic changes that give rise to resistance to malaria. Erythrocytes from individuals with erythropoietic protoporphyria (EPP) have low levels of the final enzyme in the heme biosynthetic pathway, ferrochelatase. Cells from these patients are resistant to the growth of Plasmodium falciparum malarial parasites. This phenomenon is due to the absence of ferrochelatase and not an accumulation of substrate, as demonstrated by the normal growth of P falciparum parasites in the EPP phenocopy, X-linked dominant protoporphyria, which has elevated substrate, and normal ferrochelatase levels. This observation was replicated in a mouse strain with a hypomorphic mutation in the murine ferrochelatase gene. The parasite enzyme is not essential for parasite growth as Plasmodium berghei parasites carrying a complete deletion of the ferrochelatase gene grow normally in erythrocytes, which confirms previous studies. That ferrochelatase is essential to parasite growth was confirmed by showing that inhibition of ferrochelatase using the specific competitive inhibitor, N-methylprotoporphyrin, produced a potent growth inhibition effect against cultures of P falciparum. This raises the possibility of targeting human ferrochelatase in a host-directed antimalarial strategy.

Influence of meteorological data on sun tolerance in patients with erythropoietic protoporphyria in France.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare metabolic disorder, characterized by photosensitivity, caused by errors of the haem biosynthetic pathway. Avoidance of sun exposure is recommended; however, some patients suggested a paradoxical improvement of symptoms when they move to sunny areas. OBJECTIVES: In a national French study, we sought to investigate the influence of sun exposure on EPP symptoms. MATERIALS AND METHODS: We used a national transversal observational study by questionnaire. Patients were selected from the national record of the Centre Français des Porphyries (French Porphyrias referral centre). Sun exposure level by geographic area was assessed using climate data provided by the French national meteorological service (Météo France). RESULTS: Eighty-nine patients were included. We notably observed that 40% of patients declared an improvement in their tolerance of sun exposure after repeated sun exposures. In the more sunny areas, the intensity of the pain was lower (r = -0·26) and the duration of the sun exposure responsible for flares was longer (r = 0·39) than in the areas that were less sunny (P < 0·05). CONCLUSIONS: This study proposes a benefit of natural progressive sun exposure for patients with EPP.