Early diagnosis and treatment of giant cell arteritis (GCA) is crucial for preventing ischemic complications. Multiple serological markers have been identified; however, there is a distinct lack of predicting markers for GCA relapse and complications. Our main objective was to identify serological parameters in a large cohort of treatment-naïve GCA patients, which could support clinicians in evaluating the course of the disease. Clinical data was gathered, along with analyte detection using Luminex technology, ELISA, and nephelometry, among others. Unsupervised hierarchical clustering and principal component analysis of analyte profiles were performed to determine delineation of GCA patients and healthy blood donors (HBDs). Highest, significantly elevated analytes in GCA patients were SAA (83-fold > HBDs median values), IL-23 (58-fold), and IL-6 (11-fold). Importantly, we show for the first time significantly changed levels of MARCO, alpha-fetoprotein, protein C, resistin, TNC, TNF RI, M-CSF, IL-18, and IL-31 in GCA versus HBDs. Changes in levels of SAA, CRP, haptoglobin, ESR, MMP-1 and MMP-2, and TNF-alpha were found associated with relapse and visual disturbances. aCL IgG was associated with limb artery involvement, even following adjustment for multiple testing. Principal component analysis revealed clear delineation between HBDs Blaž Burja and Julia Feichtinger shared first co-authorship, authors contributed equally to the work. Rheumatology in Slovenia: Clinical practice and translational researchElectronic supplementary material The online version of this article (https://doi.org/10.1007/s10067-018-4240-x) contains supplementary material, which is available to authorized users. and GCA patients. Our study reveals biomarker clusters in a large cohort of patients with GCA and emphasizes the importance of using groups of serological biomarkers, such as acute phase proteins, MMPs, and cytokines (e.g. TNF-alpha) that could provide crucial insight into GCA complications and progression, leading to a more personalized disease management.

Serum amyloid A (SAA) is a sensitive inflammatory marker rapidly increased in response to infection, injury or trauma during the acute phase. Resolution of the acute phase and SAA reduction are well documented, however the exact mechanism remains elusive. Two inducible SAA proteins, SAA1 and SAA2, with their variants could contribute to systemic inflammation. While unconjugated human variant SAA1α is already commercially available, the variants of SAA2 are not. Antibodies against SAA have been identified in apparently healthy blood donors (HBDs) in smaller, preliminary studies. So, our objective was to detect anti-SAA and anti-SAA1α autoantibodies in the sera of 300 HBDs using ELISA, characterize their specificity and avidity. Additionally, we aimed to determine the presence of anti-SAA and anti-SAA1α autoantibodies in intravenous immunoglobulin (IVIg) preparations and examine their effects on released IL-6 from SAA/SAA1α-treated peripheral blood mononuclear cells (PBMCs). Autoantibodies against SAA and SAA1α had a median (IQR) absorbance OD (A450) of 0.655 (0.262–1.293) and 0.493 (0.284–0.713), respectively. Both anti-SAA and anti-SAA1α exhibited heterogeneous to high avidity and reached peak levels between 41–50 years, then diminished with age in the oldest group (51–67 years). Women consistently exhibited significantly higher levels than men. Good positive correlation was observed between anti-SAA and anti-SAA1α. Both anti-SAA and anti-SAA1α were detected in IVIg, their fractions subsequently isolated, and shown to decrease IL-6 protein levels released from SAA/SAA1α-treated PBMCs. In conclusion, naturally occurring antibodies against SAA and anti-SAA1α could play a physiological role in down-regulating their antigen and proinflammatory cytokines leading to the resolution of the acute phase and could be an important therapeutic option in patients with chronic inflammatory diseases.

Background The association of the ABO blood group with COVID‐19 disease has been confirmed by several studies, with the blood group A patients being more susceptible and prone to a more severe clinical course of the disease. Additionally, several authors also addressed the association of ABO‐types and the levels of anti‐SARS‐CoV‐2 antibodies in convalescents, mostly supporting a theory that the non‐O blood group convalescents present with higher levels of anti‐SARS‐CoV‐2 antibodies. Study Design and Methods Since previous findings were based on small convalescent cohorts, we quantified the anti‐SARS‐CoV‐2 antibody levels in a total of 3187 convalescent plasma donors with three commercial serological and one standard neutralizing antibody test. The majority of donors had undergone a mild form of the disease and the median time of sampling was 66 days after diagnosis. Results None of the antibody quantitation results showed any significant association with the ABO blood group types. The same result was evident in the subgroup of vaccinated individuals (n = 370) and the subgroups when stratified according to post‐COVID‐19 periods (0–60, 60–120, and 120–180 days). Conclusion In conclusion, we found no evidence to confirm that the ABO blood group types influence the level of SARS‐CoV‐2 antibody response in COVID‐19 convalescent plasma donors.

BackgroundNaturally occurring autoantibodies (Abs) against acute phase proteins (APPs), such as anti-serum amyloid A1 (SAA1) Abs have already been identified in sera of healthy individuals, as well as in patients with autoimmune diseases (1). Currently however, no method exists for simultaneous detection of multiple Abs against APPs.ObjectivesTo develop a bead-based duplex immunoassay for simultaneous detection of IgG anti-SAA1 and anti-alpha 1 acid glycoprotein (AGP) Abs and quantify their levels in sera of healthy blood donors (HBD), and patients with systemic autoimmune diseases, as well as in intravenous immunoglobulin preparation (IVIg).MethodsFluorescently labeled MagPlex microspheres (Luminex Corp) were used to covalently bind SAA1 and AGP. Sera samples (diluted 1:20) were added to a 96-well microtiter plate and incubated with SAA1- and AGP-coupled microspheres for 2h. Subsequently, PE-conjugated anti-human IgG Abs were added to each well, incubated for 30 min, resuspended in PBS-1%BSA and analysed using the MagPix system (Biomedica, GmbH).Abstract THU0040 – Figure 1 Levels of antibodies against SAA1 (A) and AGP (B) in HBD as compared to patients with systemic autoimmune diseases. Shown is median and IQR. 5th and 95th percentile of MFI values in HBD are indicated with dotted lines; *p<0.05; **p<0.01. ?SAA1, serum amyloid A1; AGP, alpha 1 acid glycoprotein; MFI, median fluorescence intensity; HBD, healthy blood donors; GCA, patients with giant cell arteritis; IgAV, immunoglobulin A vasculitis; SLE, systemic lupus erythematosus; SSc, systemic sclerosis; APS, antiphospholipid syndrome; ERA, early rheumatoid arthritis.Abstract THU0040 – Figure 2 Presence of antibodies against SAA1 and AGP in IVIg. ?IVIg, intravenous immunoglobulin G; SAA1, serum amyloid A1; AGP, alpha 1 acid gycoprotein; MFI, median fluorescence intensity.Sera samples were collected from HBD (n=55), patients with giant cell arteritis (GCA; n=30), immunoglobulin A vasculitis (IgAV; n=30), systemic lupus erythematosus (SLE; n=20), systemic sclerosis (SSc; n=27), antiphospholipid syndrome (APS; n=19) and early rheumatoid arthritis (ERA; n=20). Ab levels were determined also in IVIg (Octapharma AG).ResultsWe observed the presence of both, anti-SAA1, and anti-AGP Abs in sera of HBD, as well as in patients with GCA, IgAV, SLE, SSc, APS and ERA.GCA patients had significantly higher anti-SAA1 levels (median (IQR) MFI was 2163 (1113- 3048)) as compared to SSc (816 (480-1462); p<0.01) and ERA (886 (722-1596); p<0.05) patients. Levels of anti-AGP Abs were also significantly higher in sera of GCA patients (495 (298-872)) as compared to ERA (213 (130-338); p<0.01) and APS (264 (154-399); p<0.05) patients. No difference in anti-SAA1 or anti-AGP levels was observed between HBD and the tested groups of patients (Figure 1).Substantial amounts of anti-SAA1 Abs were observed in serially diluted IVIg, while there were ∼4-fold less anti-AGP Abs detected (Figure 2), which corresponds also to the ratio found in HBD (Figure 1).ConclusionSerum IgG Abs against SAA1 and ...

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