An hypothetical model for the pathogenesis of sarcoidosis is presented which is compatible with its generalized nature, lack of an apparent etiologic agent and biochemical difference from other granulomas, including marked elevation of angiotensin converting enzyme.
New normal ranges of serum ACE level were determined for each genotype, and found to be 22% more sensitive overall than the conventional normal range and 39% more so for II type, suggesting an advantage for diagnosis and assessment of the disease activity of sarcoidosis.
ACE insertion/deletion (I/D) gene polymorphism has been reported to have an association with SACE levels in sarcoidosis, but no evidence of an association between angiotensin II receptor gene polymorphism and SACE in this disease has been found.
We earlier reported that ACE and its enzymatic product, angiotensin II (A-II), might play a role in maintaining macrophage/T lymphocyte alveolitis by enhancing an accessory function of macrophages in chronic active cases with sarcoidosis.
Increased serum calcium and serum angiotensin-converting enzyme activity have been associated with clinical sarcoidosis but have also occasionally been described in association with Hodgkin lymphoma and non-Hodgkin lymphoma without evidence of sarcoidosis.
There was a striking over-representation of the ACE I/D genotype DD in patients with sarcoidosis and their families as compared with controls of the study and well founded genotype frequencies from the literature.
We conclude that the ACE I/D polymorphism has no role in sarcoidosis susceptibility in European whites and that it is not a regulatory variant in this disease.
Synthetic substrates were developed for the determination of ACE activity in various biological fluids, mostly human plasma, for the diagnosis of sarcoidosis and other granulomatous diseases.
The present authors conclude that in African-Americans, the angiotensin converting enzyme, vitamin D receptor, and tumour necrosis factor-alpha genes are not significant risk factors for sarcoidosis susceptibility.
ACE and sIL2-R serum levels were significantly higher in M. tuberculosis positive sarcoidosis independent of the HLA-DRB1 specificity, but did not differ between acute and chronic disease course alone.
In conclusion, the present authors recommend the use of new, genotype-specific reference values for serum angiotensin-converting enzyme levels, especially to improve the sensitivity and specificity of tests for angiotensin-converting enzyme in the follow-up of sarcoidosis.
A boy was diagnosed as having juvenile sarcoidosis because he presented with cervical and pulmonary lymphadenopathy with epitheloid cells and granuloma formation and high angiotensin converting enzyme.Later, a liver abscess was diagnosed.
In conclusion, the results showed that the TNF-alpha genotype could be a significant risk factor for sarcoidosis, whereas the risk of sarcoidosis due to the ACE genotype was not substantially elevated.