Bluegreen> this is the first post and the FIRST time I have EVER seen someone else suggest my theory as plausible.(more or less)
"Firstly there is the anti BPI ANCA which, is thought to be present early in the disease, and therefore presumed to be associated with the defect in CFTR."
(read my lips >bpi associated with CFTR)
EXACTLY.
BINGO.
My theory has been all along that at the>minimum< anca to bpi is a co-factor in disease progression. I have been maintaining ALL ALONG that EVERYONE was focused on CFTR and ignoring bpi-anca. I continue to believe that EARLY TREATMENT in CF with bpi-21 BEFORE symptoms of CF will at least DELAY CF progression. YESSSS, I am thrilled that someone FINALLY sees what I have seen all along for perhaps 5 years now.
And YES>I have been saying ALL ALONG that BPI-21 is invisible to ANCA. >imo its the perfect solution.
Here is the rest of the article. ENJOY
More specifically, sera from CF patients with and without vasculitis have been reported to contain ANCA directed against bactercidal permeability increasing protein (BPI) (11, 29, 30). BPI is a 55-kDa membrane associated cationic protein that forms an important part of defence system against gram negative bacteria, as it binds to LPS, it neutralises endotoxin and opsonizes bacteria (31-33).
Zhao et al (11) reported that 60 out of 66 patients with CF had IgA or IgG autoantibodies to the neutrophil granule protein BPI.In the small proportion of patients with secondary vasculitis, the levels of these antibodies were higher. The BPI autoantibody levels correlated with reduction in lung function, and the presence of secondary vasculitis. The association between anti BPI autoantibodies and severity of the lung disease was also observed by Mahadeva et al (29) who reported that 55% and 70% of 148 adults patients with CF, had IgA and IgG anti BPI antibodies respectively. Sediva et al (30) reported that 51 of 71 children with CF were positive for BPI ANCA. In contrast to adult patients, there was no correlation observed between anti-BPI antibodies and severity of the impairment of lung function.
Two types of ANCA relevant to CF have been proposed (30). Firstly there is the anti BPI ANCA which, is thought to be present early in the disease, and therefore presumed to be associated with the defect in CFTR. BPI may be more easily released from the azurophilic granules of the neutrophils, encouraging antibody formation. Consequently these antibodies would block BPI, resulting in ineffective immune response and infection with Pseudomonas species. In fact, Pseudomonas colonisation is associated with higher levels of IgA anti BPI antibodies, which inhibit BPI induced phagocytosis, and therefore may contribute to more severe lung damage (29). Conversely, anti PR 3 ANCA may be a result of recurrent infections occurring over many years (30). BPI expresses a protective activity against lipopolysaccharide induced injury on vascular endothelial cells (34). Thus anti BPI antibodies by interfering with this particular function may conciliate vasculitic inflammation. Whether this particular mechanism contributes to vasculitis in CF remains an issue of speculation.
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