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Global Translational Medicine                                          AA amyloidosis in rheumatoid arthritis



            1.6. Objective                                     AA deposition values. A significance level of P < 0.05 was

            This study aims to determine the prevalence and severity   considered statistically significant.
            of systemic AA amyloidosis (sAAa) in RA, assess the   For comparisons between two datasets, the most
            prevalence and extent of GI AA deposits (giAAa) in   stringent statistical criteria in Microsoft Excel were
            various tissue structures of the GI tract, and characterize   applied, using a two-tailed distribution (parameter=“2”)
            the progression of AA deposition within the GI tract. In   and assuming unequal variance (not homoscedastic,
            addition, this study seeks to evaluate the relationship   parameter=“-3”).
            between sAAa and giAAa, investigate the impact of sAAa   The mean age of patients varied within the observed
            and giAAa on mortality, and clarify the diagnostic value of   minimum and maximum values, and the distribution of
            GI biopsy in AA amyloidosis.                       AA deposits followed a normal (Gaussian) distribution,
                                                               characterized by a bell-shaped curve.
            2. Methods
                                                                 The correlation between sAAa and giAAa was assessed
            2.1. Patients (autopsy population)                 using Pearson’s chi-squared (χ ) test. 51
                                                                                       2
            At the National Institute of Rheumatology, 9,475 patients
            died between 1969 and 1992. Among them, 161 had RA   3. Results
            and underwent autopsy. 3                           3.1. Demographics of patients with sAAa and/or
              The clinical diagnosis of RA in these patients was   giAAa
            established based on the criteria of the American   sAAa was identified in 34 (23.13%) of 161 patients with
            College of Rheumatology.  The patient histories and   RA. Tissue blocks from at least one segment of the GI tract
                                  44
            clinical protocols were reviewed by co-author Ágnes   (stomach, small intestine, or large intestine) were available
            Apáthy, a rheumatologist and neurologist. Autopsies and   for 31 (91.18%) of these 34 patients.
            histopathological evaluations were conducted by Miklós   In 29 of the 31  patients (93.55%) with available GI
            Bély.
                                                               tissue,  AA  deposits  were  detected in  branches  of blood
            2.2. Methodology                                   vessels of varying calibers and various tissue structures of
                                                               the GI tract. In contrast, 2 (6.45%) of the 31 patients with
            In this study, the term “GI tract” refers specifically to the   sAAa did not exhibit histologically detectable AA deposits
            stomach, small intestine, and large intestine; other sections,   in the GI tract, and these cases were considered as latent-
            such as the oral cavity, pharynx, and esophagus, were not   stage giAAa.
            evaluated separately.
                                                                 A strong positive correlation was observed between
              The presence and extent of sAAa and giAAa were   sAAa (n = 34) and giAAa (n = 29) (c = 1.0, χ  = 142.06,
                                                                                                     2
            determined histologically through a detailed examination   P < 0.000). However, there was no significant difference
            of eight organs (kidneys, heart, pancreas, GI tract, liver,   between the average AA deposition in sAAa and giAAa
            lungs, skin, and brain).                           (P < 0.386).

              AA deposition in various tissue structures of these organs   Table  1 summarizes the demographics, onset, and
            was  diagnosed  histologically  according  to  Romhányi’s   duration of disease for the total study population (N = 161),
            method,  utilizing a modified and more sensitive Congo   as well as for subgroups with sAAa (n = 34) and without
                  45
            red staining technique.  AA deposits were further   sAAa (n = 127). In addition, it presents data for patients
                                46
            identified in serial sections using immunohistochemical    with giAAa (n = 31), categorized into latent (n = 2), mild
                                                         47
            and histochemical methods. 48-50                   (n = 17), and severe (n = 12) AA deposits in the GI tract.
            2.3. Statistical analysis                            A comparison of age, sex, RA onset, and disease
                                                               duration at the time of death revealed no statistically
            The  demographic  characteristics  of  different  patient   significant differences in survival time, disease onset,  or
            cohorts were analyzed using the Student’s (Welch) t-test   disease duration between patients with sAAa (n = 34) and
            to compare age, sex, disease onset, and disease duration at   the total study population (n = 161) (P = 0.321, P = 0.376, P
            the time of death between patients with and without sAAa,   = 0.554). No significant differences were observed between
            as well as between patients with giAAa with mild (<0.8   female patients (P = 0.800, P = 0.631, P = 0.682) and male
            deposits/patient) or severe (≥0.8/patient) AA deposits. 51
                                                               patients (P = 0.348, P = 0.565, P = 0.688). Similarly, no
              The threshold value of 0.8 for classifying mild and severe   statistically significant differences were found between
            cases was determined based on the Gauss distribution of   patients with  sAAa (n =  34)  and  those  without  sAAa


            Volume 4 Issue 1 (2025)                        106                              doi: 10.36922/gtm.5325
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