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Global Translational Medicine AA amyloidosis in rheumatoid arthritis

Table 2. Statistical correlations (P-values) between female and male RA patients with sAAa and giAAa at different stages
Patient cohorts with RA Age Onset of RA Duration of RA
RA patients (n=161) versus sAAa (n=34 of 161) 0.321 0.376 0.554
Female: n=116 of 161 versus n=29 of 34 0.800 0.631 0.682
Male: n=45 of 161 versus n=5 of 34 0.348 0.565 0.688
With sAAa (n=34 of 161) versus without sAAa (n=127 of 161) 0.213 0.262 0.462
Female: n=29 of 34 versus n=87 of 127 0.745 0.528 0.593
Male: n=5 of 34 versus n=40 of 127 0.297 0.521 0.662
With sAAa (n=34 of 161) versus with giAAa (n=31 of 34) 0.811 0.883 0.867
Female: n=29 of 34 versus n=26 of 31 0.623 0.820 0.861
Male: n=5 of 34 versus n=5 of 31 1.000 1.000 1.000
With latent giAAa (n=2 of 31) versus with mild giAAa (n=17 of 31) 0.364 – –
a
Female: n=2 of 2 versus n=0 of 17 0.676 – –
Male: n=0 of 2 versus n=4 of 17 – – –
With latent* giAAa (n=2 of 31) versus with severe giAAa (n=12 of 31) 0.115 – –
Female: n=2 of 2 versus n=8 of 12 0.050 – –
Male: n=0 of 2 versus n=4 of 12 – – –
With mild giAAa (n=17of 31) versus with severe giAAa (n=12 of 31) 0.363 0.127 0.560–
Female: n=2 of 2 versus n=8 of 12 0.048 0.436 0.030
Male: n=0 of 2 versus n=4 of 12 – – –
Note: Amyloid A deposits were not found (detected) in tissue blocks of the gastrointestinal tract of two patients with sAAa, which were considered as
a
latent-stage giAAa.
Abbreviations: giAAa: Gastrointestinal amyloid A amyloidosis; RA: Rheumatoid arthritis; sAAa: Systemic amyloid A amyloidosis.
3.3. Immunohistochemical characteristics of sAAa deposits were not observed in the brain. The most extensive
and/or giAAa deposits were found in the kidneys and heart (Table 3).
AA deposits exhibit a positive reaction for anti-human In 22 (64.71%) of 34 RA patients with sAAa, the average
AA components when subjected to immunohistochemical amount of AA deposits per patient was <0.8, which was
staining (Figure 3). The anti-human AA reaction is highly classified as mild. In 12 (35.29%) of 34 patients, the AA
specific; however, minimal AA deposits may not be deposit load was >0.8, classifying it as severe (Patients
detected. 23 – 34 in Table 3). Table 3 and Figures 5-7 summarize
the quantitative differences in AA deposits across various
3.4. Histochemical characteristics of sAAa and/or organs (kidneys, heart, pancreas, GI tract, liver, lungs, skin,
giAAa and brain) in 34 RA patients with sAAa.
AA deposits associated with sAAa exhibit sensitivity to The prevalence and amount of AA deposits in patients with
performate pre-treatment (1 s) and variable resistance sAAa followed a generally parallel trajectory (Table 3), aligning
to KMnO oxidation, depending on the exposure time: with the trend lines of incremental increase (Figure 5), except
4
(i) resistant for 30 sec – 1 min, (ii) resistant/sensitive for during the early and terminal stages of amyloid deposition.
3 – 5 min, and (iii) sensitive for 10 min. The histological Figure 5 illustrates the prevalence and amount of AA deposits
and histochemical characteristics of sAAa and/or GI AA across eight organs in 34 RA patients with sAAa. In the early
deposits are demonstrated using light and polarization stage of sAAa, AA deposition started abruptly, while in the
microscopy in Figure 4.
terminal stage, AA deposition accelerated again, resulting in
3.5. Characteristics of sAAa an exponential increase in the growth curve. In some patients,
moderate differences between the prevalence and severity of
The accumulation of AA deposits in various organs sAAa were observed, primarily due to the unavailability of
followed a progressive and primarily linear trajectory, with tissue samples from certain organs.
an abrupt onset and an exponential increase in the terminal
stage. Amyloid deposition most frequently affected the GI The prevalence and amount of AA deposits in various
tract and pancreas, compared to other organs, while AA organs of 34 RA patients with sAAa followed a generally

Volume 4 Issue 1 (2025) 108 doi: 10.36922/gtm.5325