Page 128 - GTM-4-1

Global Translational Medicine AA amyloidosis in rheumatoid arthritis

sAAa prevalence and mortality in these studies were
Cl+/Cl- – – Cl+ – – – 9 often overestimated or underestimated when compared
to our results. This discrepancy likely stems from limited
Cause of death cAAa rAAa-U rAAa-U cAAa – – 25 microscopic examination of various organs or the
application of non-specific staining methods (Table 6).
53-76
Unfortunately, few studies have specifically addressed the
Table 5. Mortality of systemic amyloid A amyloidosis (n=34), gastrointestinal amyloid A amyloidosis (n=31), and their amyloid A deposits per patient
relationship between sAAa and AA deposition in different
Avg giAAa 0.65 0.00 1.53 1.42 1.83 1.38 31 organs. To our best knowledge, no prior study has provided
a detailed analysis of the rate of AA deposition in the GI
tract, nor its relationship to sAAa and mortality.
The precursors of AA protein fibrils are synthesized
Avg sAAa 0.738 1.193 0.325 0.172 0.435 0.258 34 by the liver and circulate in the bloodstream, where they
are deposited in various organs. The concentration of
these precursors in the blood is influenced by the balance
Accompanying disease DM Hypertension – Operated breast cancer RA – 20 cardiovascular system and spreads through the bloodstream,
between their production and elimination.
primarily
involves
amyloidosis
Systemic
the
whereas organ- or tissue-limited (localized) amyloidosis
is not directly linked to systemic circulation and remains
confined to specific tissues.
As previously stated: “All
74,79
forms of amyloidosis related to the circulation of blood are
74(p.48),79(pp.67-68),80(pp.212-213)
.
circulation are isolated (localized).”
Cause of death Multifocal myocardiocytolysis Uremia Uremia Circulatory failure Bronchopneumonia Peritonitis-sepsis Notes: Basic disease: Underlying disease related to death; Complication: A direct consequence of the basic disease that contributed to death; Associated (Accompanying) disease: A significant disorder without a direct causal role in death; Pr. n 0] /y: Protocol number/year; CoD: Cause of death – Uremia (U) or Uremia due to massive AA de
The rate and extent of AA deposition in different organs
may be influenced by differences in blood supply per unit
volume, local tissue factors, and the potential for incidental
amyloid elimination.
74,79
Amyloidosis is a progressive and cumulative process,
Complication 2 sAAa – – Epicarditis sAAa Penectomy 34 14 initially affecting only a few tissue structures in select
organs before progressively involving more structures as
3,74,79-82
the disease advances.
The degree of AA deposition – both in terms of prevalence
Complication 1 Bronchiolitis obliterans sAAa sAAa sAAa Hypertension sAAa 34 and amount – in various organs and tissue structures
follows the same progressive and cumulative pathological
process, as demonstrated in Figures 5,7,8 and 10. The
steady and continuous (consistently linear) accumulation
of AA across different tissue structures and organs suggests
a gradual deposition process.
With the exception of the early (latent) and late stages of
Basic disease Atherosclerosis RA-colitis-nephrolithiasis of GI tract were not available; RA: Rheumatoid arthritis; JCA: Juvenil chronic arthritis. amyloidosis, AA accumulation in different tissue structures
and organs generally follows a linear trajectory. The onset
of AA deposition varies across organs, which explains the

RA RA RA RA 34 variability observed in the early stage of amyloidosis.
In the terminal stage, a rapid (exponential) increase in AA
f/m f f f f f f accumulation occurs, likely due to massive amyloid deposition
Pr. n 0] /y 245/88 101/90 306/90 287/91 52/92 183/92 34 in the kidneys, which leads to complete renal failure and the
inability to excrete amyloid precursors in end-stage rAAa.
The rate of amyloid deposition was comparable in
Total 29 30 31 32 33 34 Total patients with mild and severe amyloidosis, as well as across

Volume 4 Issue 1 (2025) 120 doi: 10.36922/gtm.5325