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Up regulation of C3, C4, and soluble intercellular adhesion molecule-1 co-expresses with high sensitivity C reactive protein in familial hypoalphalipoproteinaemia: further evidence of inflammatory activation


Objective: To test the working hypothesis that inflammation underlying precocious and severe coronary atherosclerotic disease in familial hypoalphalipoproteinaemia (FH) can be mediated by up regulation of the innate immune response.

Methods and results: 52 patients with FH were compared with 52 healthy controls with regard to immune system markers such as C reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), C3c, and C4. Patients differed from controls in their significantly lower concentrations of high density lipoprotein cholesterol (30.2 (4.0) v 50.5 (13.6) mg/dl, p < 0.0001) and apolipoprotein A I (113.2 (19.9) v 148.7 (25.1) mg/dl, p < 0.0001) and their higher triglyceride (139.3 (63.2) v 81.4 (41.7) mg/dl, p < 0.0001) and CRP plasma concentrations (median 0.33 mg/dl, range 0.02–4.66 mg/dl v median 0.07 mg/dl, range 0.02–0.85 mg/dl, p < 0.0001), but not in their total cholesterol and low density lipoprotein cholesterol concentrations. Concentrations of protein complement were higher in patients (C3: 150.8 (42.3) v 101.9 (17.4) mg/dl, p < 0.0001; C4: 35.5 (13.6) v 22.8 (6.4) mg/dl, p < 0.0001) and sICAM-1 concentrations were more than double those found in the controls (335.1 (107.5) v 159.5 (78.2) mg/dl, p < 0.0001).

Conclusions: Increased concentrations of sICAM-1, C3c, and C4 co-express with high concentrations of CRP in FH. The lack of signs and symptoms of inflammation in these patients may suggest that the immune response is up regulated as part of the pro-inflammatory mechanisms that are activated in this atherogenic condition.

  • CRP, C reactive protein
  • ELISA, enzyme linked immunosorbent assay
  • FH, familial hypoalphalipoproteinaemia
  • HDL, high density lipoprotein
  • ICAM-1, intercellular adhesion molecule-1
  • sICAM-1, soluble intercellular adhesion molecule-1
  • high density lipoprotein
  • HDL
  • hypoalphalipoproteinaemia
  • sICAM-1
  • soluble intercellular adhesion molecule-1
  • complement
  • atherosclerosis

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