Serum amyloid A as a marker of ankylosing spondylitis activity

Serum amyloid A protein A (SAA) is a normal serum protein (serving as a precursor of fibrillar tissue protein AA), synthesized in the liver and a rapidly responding marker of the acute phase of inflammation. A constant high concentration of SAA is one of the factors in the development of AA-amyloidosis. As a rule, secondary amyloidosis develops in patients with long-term and poorly controlled inflammatory diseases, including rheumatic diseases, one of which is ankylosing spondylitis (AS).Objective: to assess the level of SAA in AS patients and its relationship with indicators of disease activity.Patients and methods. The study included 124 patients with AS who met the modified New York 1984 criteria. The disease activity and functional status of patients were assessed according to the recommendations of Russian experts. SAA and CRP, ESR in blood serum were measured in all patients.Results and discussion. The median SAA concentration was 12.5 mg/L [4; 71.6]. Of 124 patients, 31% had SAA levels <5 mg/L and 69% had >5 mg/L. A strong correlation was found between the levels of SAA and CRP (r=0.80, p<0.000001), no significant relationship was found between SAA and ESR (r=0.31, p=0.92). The correlation between the AS activity according to the BASDAI index and SAA was weak (r=0.3, p<0.002), the correlation with ASDAS-CRP was moderate (r=0.54, p<0.00001).Conclusion. A statistically significant relationship was found between SAA and CRP levels, as well as the AS activity indices. Research has shown that SAA can be used as one of the markers of inflammation in AS.

AA-amyloidosis in autoinflammatory diseases

AA amyloidosis complicates various chronic inflammatory disorders and is characterized by the accumulation of amyloid fibrils composed of serum amyloid A protein, an acute phase reactant. In recent decades, the role of chronic infections and rheumatoid arthritis in the ethiology of AA amyloidosis have decreased significantly as a result of their treatment improvement, whereas both monogenic (familial Meditarranean fever, cryopirin-associated periodic syndrome, etc.) or polygenic (ankylosing spondilitis, psoriatic arthritis, adult onset Still’s disease, etc) autoinflammatory diseases more frequently account for AA-amyloidosis today. Autoinflammatory diseases are a consequence of innate immunity disorders although the latter can contribute to the pathogenesis of autoimmune diseases as well. In patients with autoinflammatory diseases, the suppression of inflammation, even subclinical, is essential to prevent development or progression of AA amyloidosis. The choice of inflammatory agents that can be used to achieve this aim depends on the pathogenesis of autoinflammation, e.g. key mediators that are involved in the activation of inflammatory cascade.

Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

Shear wave elastography evaluation of liver, pancreas, spleen and kidneys in patients with familial mediterranean fever and amyloidosis

Objectives: Amyloid deposits in a visceral organ can contribute to tissue stiffness that could be measured with shear wave elastography (SWE). We aimed to investigate changes in organ stiffness in conjunction with laboratory parameters in patients with Familial Mediterranean Fever (FMF) and amyloidosis. Methods: This prospective study included 27 FMF patients, 11 patients with amyloidosis, and 38 healthy controls. Median shear wave elasticity values of the liver, spleen, both kidneys, and pancreas on SWE were compared among study and control groups. The mean values of CRP (C-reactive protein) and ESR (erythrocyte sedimentation rate) were compared by the t–test and the median of SAA (serum amyloid A protein) was compared with the Mann–Whitney U test between FMF groups with and without amyloidosis. Spearman’s correlation analysis was performed to reveal the association between stiffness values and laboratory parameters. Results: The median liver, spleen, kidney, and pancreas elasticity values were significantly higher in the FMF group with amyloidosis compared to control subjects. The median kidney stiffness values in the FMF group with or without amyloidosis were significantly higher compared to control subjects. Median liver stiffness values in FMF patients with amyloidosis were significantly higher than FMF patients without amyloidosis. There were statistically significant positive correlations between the CRP (p = 0.001, r = 0.56), ESR (p = 0.001, r = 0.61), and SAA (p = 0.002, r = 0.53) levels with spleen stiffness, and CRP (p = 0.006, r = 0.48) and ESR (p = 0.001,r = 0.61) levels with pancreas stiffness, and ESR (p = 0.004, r = 0.51) levels with the left kidney stiffness. Conclusion: SWE could be a potential tool for noninvasive follow-up of FMF patients and also amyloid deposition. Advances in knowledge: Both acute inflammation and amyloidosis in the FMF patients could increase organ stiffness.

Comparison of metabolic, oxidative and inflammatory status of Simmental × Holstein crossbred with parental breeds during the peripartal and early lactation periods

The aim of the research reported in this paper was to evaluate plasma concentrations of energy, oxidative and inflammatory biomarkers of Simmental (sire) × Holstein (dam) crossbred cows, in comparison with the two parental breeds during the peripartal and early lactation periods and to estimate the effects of heterosis for these traits. Thirty-three animals, managed under the same conditions, 8 Simmental (SI), 9 Holstein (HO) and 16 crossbred (CR) cows were enrolled in this study. Glucose, non-esterified fatty acids (NEFA), β-hydroxybutyrate (BHB), total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatine kinase (CK), total protein, albumin, creatinine and urea were determined in blood sampled at six different time points (30 ± 3 and 15 ± 3 d before the expected calving date, at calving and 15, 30 and 60 d after calving). Furthermore, derived reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), interleukin-6 (IL-6), haptoglobin (Hp) and serum amyloid A protein (SAA) were determined to evaluate inflammatory and oxidative status. Results showed that the CR group had significantly lower average values of glucose and NEFA when compared to HO group; signifcantly lower values of urea than SI group and significantly higher values of creatinine than HO. Furthermore, CR cows showed the lowest average value of d-ROMs with respect to SI and HO parental breeds. Finally, the average value of haptoglobin was significantly lower in CR and HO groups, when compared to SI group. As for the heterosis we found the highest (positive) percentage for CK (98%) and BAP (47%) and the lowest (negative) percentage for OSi (−75%) and d-ROMs (−39%). A negative percentage was also found for the glucose (−11%) and NEFA (−20%) toward the Simmental parental breed. Our results suggest a different response among the three genetic groups during the peripartal and early lactation periods. In particular, CR and SI cows seem more adaptable regarding energy metabolism and oxidative status. Heterosis led to a positive effect on those parameters in Simmental (sire) × Holstein (dam) crossbred cows F1 population (50% Simmental and 50% Holstein).

AB0072 SERUM AMYLOID A PROTEIN (SAA) IN ANKYLOSING SPONDYLITIS AND THE RELATIONSHIP WITH SYSTEMIC INFLAMMATION

Background:Serum amyloid A protein (SAA) likely has a critical role in control and possibly propagation of the primordial acute phase response and is the precursor of AA amyloid fibrils. Prolonged elevations in SAA are the major inciting factor for AA amyloidosis developing in chronic inflammatory diseases. In Russia 2-4% of patients with ankylosing spondylitis (AS) have secondary (AA) amyloidosis.Objectives:To study the level of SAA in AS its relationship with indicators of disease activity.Methods:124 patients with AS (according to mNYC 1984) 70 men, 54 women, of whom HLA B 27 positive 91.1% mean age 38.1 (± 12.9), age at the onset of the disease 23.5 (± 9.9) consecutively admitted to the clinic of the Research Institute rheumatology from February to November 2020. In addition to the standard examination (the median CRP 6.7 mg/l [1.4; 24.9], ESR 13 mm/h [7; 27], SAA was studied in all patients by the nephelometric method.Results:The median SAA in 124 patients was 12.5 mg/l [4;71.6]. Among them, 31% had normal SAA level (<5 mg/l), and 69 % - more than 5 mg/l. In 21 (17.5 %) cases, the level of SAA was increased at normal CRP levels, and only in 2 cases an increase in the level of CRP at normal SAA levels; 50 patients (40.3 %) with normal ESR had elevated SAA levels, and 7 (5.6%) - ESR exceeded the upper limits of the norm with normal SAA levels. Comparison of the average values of the levels of SAA, CRP, ESR in men and women did not reveal significant differences between them. The SAA level was weakly correlated with ESR (r = 0.2; p=0.002) and BASDAI (r=0.3; p=0.002), moderately with ASDAS-CRP (r=0.5; r<0.0001), but showed a strong association with CRP (r = 0.80; p<0.00001). Patients with elevated SAA levels (>5 mg/l) had a shorter disease duration (10 and 12 year; p<0.0004), higher ASDAS-CRP (2.9 and 2.4; p<0.003), blood CRP level (14.6 and 1.3; p<0.00001), and significantly more peripheral arthritis (60% and 39%; p<0.05) than patients with normal indicators.Conclusion:The level of SAA correlates well with indicators of AS activity, especially with the level of CRP, and can be used as an alternative indicator of disease activity.Disclosure of Interests:None declared

Methods to study the structure of misfolded protein states in systemic amyloidosis

Systemic amyloidosis is defined as a protein misfolding disease in which the amyloid is not necessarily deposited within the same organ that produces the fibril precursor protein. There are different types of systemic amyloidosis, depending on the protein constructing the fibrils. This review will focus on recent advances made in the understanding of the structural basis of three major forms of systemic amyloidosis: systemic AA, AL and ATTR amyloidosis. The three diseases arise from the misfolding of serum amyloid A protein, immunoglobulin light chains or transthyretin. The presented advances in understanding were enabled by recent progress in the methodology available to study amyloid structures and protein misfolding, in particular concerning cryo-electron microscopy (cryo-EM) and nuclear magnetic resonance (NMR) spectroscopy. An important observation made with these techniques is that the structures of previously described in vitro formed amyloid fibrils did not correlate with the structures of amyloid fibrils extracted from diseased tissue, and that in vitro fibrils were typically more protease sensitive. It is thus possible that ex vivo fibrils were selected in vivo by their proteolytic stability.

Influence of obesity on serum levels of SARS-CoV-2-specific antibodies in COVID-19 patients

SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus-2), cause of COVID-19 (Coronavirus Disease of 2019), represents a significant risk to people living with pre-existing conditions associated with exacerbated inflammatory responses and consequent dysfunctional immunity. In this paper, we have evaluated the influence of obesity, a condition associated with chronic systemic inflammation, on the secretion of SARS-CoV-2-specific IgG antibodies in the blood of COVID-19 patients. Our hypothesis is that obesity is associated with reduced amounts of specific IgG antibodies. Results have confirmed our hypothesis and have shown that SARS-CoV-2 IgG antibodies are negatively associated with Body Mass Index (BMI) in COVID-19 obese patients, as expected based on the known influence of obesity on humoral immunity. Antibodies in COVID-19 obese patients are also negatively associated with serum levels of pro-inflammatory and metabolic markers of inflammaging and pulmonary inflammation, such as SAA (serum amyloid A protein), CRP (C-reactive protein), and ferritin, but positively associated with NEFA (nonesterified fatty acids). These results altogether could help to identify an inflammatory signature with strong predictive value for immune dysfunction. Inflammatory markers identified may subsequently be targeted to improve humoral immunity in individuals with obesity and in individuals with other chronic inflammatory conditions.