Autoimmunity to protective molecules (Re: What if......)

[Guest guest]

I only now got around to reading that abstract. Very provocative.

I hadn't known about Shoenfeld.

With regards to apoptosis defects playing a role in autoimmunity,

there's some indication that autophagy can mediate programmed cell

death (see e.g., PMID: 9332326, PMID: 15530778 and PMID: 15325581).

Makes me think of the two independent autophagy genes that are

associated with Crohn's. The recent editorial on those findings

cited the role of autophagy in clearing intracellular pathogens, but

now I wonder if the role that those alleles seem to play in Crohn's

may have more to do with a reduced ability of clonally expanded T

cells to experience the full measure of contraction.

On another matter, given your experience with D3 supplementation and

my hangup with the implication that D3 supplementation can alter the

local concentration of calcitriol, another resolution (in addition

to the ability of IFNg to block feedback inhibition) is implied by

PMID: 16115686. Apparently the vitamin D binding protein (DBP)

ehances chemotaxis of neutrophils in response to the complement

fragment C5a. What's especially interesting about this paper is

that it not only claims that calcitriol abrogates the chemotaxis,

but figure 3 provides evidence that calcidiol can block this effect

of calcitriol. If this paper has merit, it implies that high-dose

D3 supplementation might enhance neutrophil chemotaxis by competing

away the bound calcitriol. That may not explain what happened to

you, but it's another angle on the matter--one that doesn't require

calcidiol to be converted to calcitriol.

>

>

> > Various proteins are capable of putting the brakes on

inflammation.

> > IL-10 is the obvious example, but there are others. So what if

the

> > autoantibody that some people generate happens to neutralize one

of

> > these " brakes " ?

>

> Here's a related thought from Y Shoenfeld. Shoenfeld is a mile-tall

> earth shaker in AI studies, editor of 6 billion symposium books and

> author of 729 planets of papers (33 papers so far in 2007).

Possibly a

> good guy to have a pubmed alert on in order to keep track of trends

> and developments in orthodox AI research. I think he seemed pretty

> thoughtful to me when I read one of his papers, but I haven't read

> much of him.

>

> The importance (to SLE) of the complement proteins mentioned below

is

> nothing flimsy. Humans that are null at certain of the complement

> genes have an SLE prevalance around 30% (sayeth Dubois). While this

> association could possibly involve chronic infection, it's also far

> from the only SLE-related factor which can be related to

apoptosis.

>

>

>

> Autoimmunity to Protective Molecules: Is it the Perpetuum Mobile

> (Vicious Cycle) of Autoimmune Rheumatic Diseases?

>

>

> e Szyper Kravitz; Yehuda Shoenfeld

>

> Summary

>

>

> Apoptotic defects and impaired clearance of cellular debris are

> considered key events in the development of autoimmunity, as they

can

> contribute to autoantigen overload and might be involved in the

> initiation of an autoimmune response. The C1q protein and

> mannose-binding lectin are activators of the complement system. The

> pentraxins are a group of highly conserved proteins including the

> short pentraxins, C-reactive protein and serum amyloid P, and the

long

> pentraxin family member, pentraxin 3, all of which are involved in

> innate immunity and in acute-phase responses. In addition to their

> role in innate immunity and inflammation, each of these proteins

> participates in the removal of damaged and apoptotic cells. In this

> article, we discuss the clinical significance of different levels

of

> these proteins, their role in the induction of or protection

against

> autoimmunity, and the presence of specific autoantibodies against

them

> in various autoimmune diseases.

>