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International
Medicine 3(1): 1-2, 2008 |
LETTER TO THE
EDITOR |
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http://im1.biz/im |
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© Truthfinding
Cyberpress (http://im1.biz/tfcp) |
MOLECULAR
PATHOGENESIS |
On a particular IgA1 as
substance X in rheumatoid arthritis: a further molecular pursuit of Hench´s legacy
Razvan Tudor Radulescu
Molecular Concepts Research
(MCR),
E-mail: ratura@gmx.net
(Received
HIGHLIGHT
For
more than half a century, various attempts have been undertaken to zero in on
the enigma of substance X, a natural molecule that had been postulated by Phil
Hench to be responsible for attenuating the course of rheumatoid arthritis
during pregnancy and obstructive jaundice. This mystery may have now been
solved by the molecular specification presented in this brief report.
ABSTRACT
Recently, the application of the peptide strings concept
and its extensions have unravelled a possible dysfunction of a subclass of
immunoglobulin A1 molecules as a potentially crucial event for the onset and
maintenance of rheumatoid arthritis. Based on additional clinical
considerations presented here, it it now proposed that this distinct IgA1
antibody may represent in its functional form the long-sought substance X that
had been inferred by Philip Hench in the late 1940s to account for the
mitigated course of rheumatoid arthritis during pregnancy and obstructive
jaundice. The solution to this major clinical puzzle advanced in this
communication may transform the diagnosis and therapy of rheumatoid arthritis
in the years to come.
KEY
WORDS
Philip Hench, Substance X, Rheumatoid arthritis,
Obstructive jaundice, Pregnancy, Immunoglobulin, Antibody, IgG1, Rheumatoid
factor, Candida albicans, Epitope, Molecular mimicry, Cross-reactivity, Autoimmunity,
Diagnosis, Treatment, IgA1, Peptide
Sir,
It has been a long time since Phil Hench communicated his important
observations on an improvement of the course of rheumatoid arthritis (RA)
during pregnancy and obstructive jaundice (1). Yet, the precise nature of the
molecule termed substance X and held responsible for this amelioration has
remained elusive to date. Already Hench himself had ascertained that "the
responsible agent is neither bilirubin nor a unisexual (female) hormone"
(1). Meanwhile, it has also become clear that, although highly effective as
therapeutics for RA, corticosteroids are not candidates for substance X either
(2).
Recently, my own investigations into the
pathogenesis and possible treatment of RA have led me to propose that a certain
variant of the immunoglobulin A1 (IgA1) molecule could, most likely as a result
of aberrant glycosylation, be dysfunctional in this disease whereas, normally,
this distinct subset of natural antibodies would be holding in check the fungus
Candida albicans and concomitantly
concealing a potentially cross-reactive epitope on IgG1 such that it is not a
subject for autoimmune reactions (3).
I am now following up on this report (3) by
suggesting that such IgA1 isoform may be the long-sought substance X. This
conjecture is supported by the fact that, interestingly, pregnancy and
obstructive jaundice share the feature of a significant increase in (local
and/or systemic) IgA levels, as measured in saliva in the former condition (4)
and in serum in the latter one (5,6). In this context, it is notable that
Hench´s observation according to which several types of (intrahepatic or
extrahepatic, biliary) jaundice had been found to be effective in attenuating
RA (1) is entirely consistent with the known increase of IgA as part of these
diseases (7). I should specify that among these accumulated IgA molecules there
ought to be IgA1 variants that- due, for instance, to saturation of modifying
enzymes- have not immediately been inactivated by a post-translational (glycosylation)
modification and thus could still assume their putative combined anti-fungal
and autoimmunity-preventive role for a given time period.
Therefore, it may be worth examining if (an increase
in) the postulated IgA1 fraction could be determined and, if so, these specific
immunoglobulins and/or (peptide) mimetics thereof might be employed to reverse
RA.
REFERENCES
1. Hench, P.S. 1949. The potential
reversibility of rheumatoid arthritis. Ann. Rheum. Dis. 8:90-96.
2. Crocker,
3. Radulescu, R.T. 2008. Peptide strings
clues to the genesis and treatment of rheumatoid arthritis: rebuilding
self-protective immunity amid fungal ruins. arXiv:0808.1283v1 [q-bio.SC].
4. Widerström L., and D. Bratthall. 1984.
Increased IgA levels in saliva during pregnancy. Scand. J. Dent. Res. 92:33-37.
5. Goldblum, R.M., G.K. Powell, and G. Van
Sickle. 1980. Secretory IgA in the serum of infants with obstructive
jaundice. J. Pediatr. 97:33-36.
6. Ohshio, G., F. Furukawa, K. Sekita, T.
Manabe, T. Tobe, and Y. Hamashima. 1985. IgA containing circulating immune
complexes and IgA anti-single stranded DNA antibodies in patients with
obstructive jaundice. Clin. Exp. Immunol. 59:435-441.
7. Chandy K.G., S.G. Hübscher, E. Elias, J.
Berg, M. Khan, and D. Burnett. 1983. Dual role of the liver in regulating
circulating polymeric IgA in man: studies on patients with liver disease. Clin.
Exp. Immunol. 52:207-218.