Background Familial Mediterranean Fever (FMF) is an autoinflammatory disease manifested by short febrile episodes of serositis. Severity of disease is linked to the occurrence of AA amyloidosis1 that involves many tissues, including the lungs2. Pulmonary hypertension (PH) is a rare complication of amyloidosis, and its natural history is not well-defined3. In addition to endothelial dysfunction, inflammatory mechanisms appear to play a significant role4.
Objectives To clarify the significance of endothelial vasoactive mediators we studied serum NO and plasma ET-1 in relation to inflammation and amyloidosis in FMF patients.
Methods We selected 53 FMF patients without amyloidosis (mean age 33.6±14.1)-I group, 49 FMF patients with amyloidosis (37.6±9.1)-II group, and 50 healthy control subjects matched for age, gender, and smoking habit. Besides other type of attacks all patients had pleuritic as well. Laboratory tests were performed in attack free period. NO and ET-1 levels were measured by Griess reaction and enzyme immunoassay, respectively. CRP was determined by immunoturbidimetric method and SAA by ELISA.
Results The levels of NO were within normal ranges in FMF patient groups, but the mean level of NO was lower in I group than in the control group (3.18±0.55μmol/l vs 8.79±2.72 μmol/l, t=14.3, p<0.000) and significantly lower in II group than in I group (2.71±0.85 μmol/l vs 3.18±0.55 μmol/l t=3.32, p<0.001). The mean level of ET-1 was increased in patient groups. It was higher in I group than in the control group (15.16±6.48 pg/ml vs 7.8.±1.99 pg/ml, t=7.89, p<0.000) and significantly higher in II group than in I group (23.9±14.14 pg/ml vs 15.16±6.48 pg/ml t=3.96, p<0.0001). Mean C-reactive protein (CRP) and serum amyloid-A (SAA) were 17.74±13.74 mg/L vs 11,88±13.79 mg/L and 33±66.6 mg/L vs 5.25±4,45mg/L, and significantly higher in II group than the mean values of I group (P<0,0001). NO levels were correlated negatively with CRP (r=-0.395, p=0,003, I group; r=-0,320, p=0,025, II group) and did not correlate with SAA in both patient groups. ET-1 levels were correlated positively with CRP and SAA in both patient groups (r=0,708, p=0,000 and r=0,416, p=0,002,respectively,I group), (r=0,495, p=0,000 and r=0,384, p=0,006, II group).
Conclusions Our study has shown that amyloidosis in FMF is associated with higher plasma levels of ET-1, raising the possibility of a pathogenetic role for endothelial dysfunction in the pathogenesis of PH in FMF-amyloidosis. Elevated levels of ET-1 should be explained by amyloid vascular deposition. At the same time our data show that increases in ET-1 plasma levels in FMF patients without amyloidosis are associated with higher serum levels of CRP and SAA, raising the possibility of pathogenetic role for low-grade systemic inflammation in the pathogenesis of PH in FMF without amyloidosis. This further supports the value of ET-1 as a marker of vascular abnormalities in FMF related PH. It is possible that the pulmonary vascular disease process associated with FMF begins early in the course of the disease.
Grateau G et al. Clinical versus genetic diagnosis of FMF. Q J Med 2000;93:223-9.
Lidar M et al. Thoracic and lung involvement in FMF. Clin Chest Med 2002;23(2):505-11.
Dingli D et al. Pulmonary hypertension in patients with amyloidosis. Chest 2001;120:1735-9.
Dorfmüller P et al. Inflammation in pulmonary arterial hypertension. ERJ 2003;22(2):358-63.
Acknowledgements We thank Anahit Davtyan, chief of the laboratory, for collaboration.
Disclosure of Interest None declared
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.