The low molecular weight fraction of human serum albumin (LMWF5A) is a biologic drug currently under clinical investigation for the treatment of osteoarthritis and the hyper-inflammation observed with severe COVID-19. In vitro investigations demonstrate that LMWF5A inhibits pro-inflammatory cytokine release (such as TNFα, IL1β, IL6, and CXCL10) as well as the activity of pro-inflammatory transcription factors (NF-κB and STAT) in immune cells stimulated through toll-like receptor (TLR) 4 using lipopolysaccharide. The aim of this investigation is to evaluate the ability of LMWF5A to suppress TLR7/8 signaling, which has been implicated in the pathology of a variety of inflammatory and autoimmune diseases including cytokine storm development and acute kidney injury in sepsis and lupus.
To evaluate this, human monocytic cell lines and peripheral blood mononuclear cells (PBMC) were activated in the presence of LMWF5A or saline using an agonist for TLR7/8 (CL075). CXCL10 release in the culture medium was then quantified by ELISA after 24 hours, and percent change was calculated versus TLR7/8-activated cells treated with saline as a diluent control.
LMWF5A dose-dependently inhibited CL075-induced CXCL10 release from macrophage-like THP-1 cells from 15-90%. Furthermore, this drug response was observed across a range of CL075 concentrations and in a variety of monocytic lineages, including primary PBMC (54%) and U937 cells (82%).
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These findings provide evidence that LMWF5A treatment suppresses TLR7/8 signaling in monocytic/macrophage lineages and suggests a role for LMWF5A in treating the dysregulation of these pathways observed in lupus nephritis as well as in COVID-19.
Hydroxychloroquine(HCQ) is a disease-modifying anti-rheumatic drug that is often used in patients with rheumatoid arthritis(RA), systemic lupus erythematosus(SLE), and other autoimmune diseases like Sjogren's Syndrome(SS) or Mixed Connective Tissue Disease(MCTD). It has been observed that in-vitro, SARS-Cov-2 viral replication is reduced by HCQ, but in doses higher than 1000mg. There is controversy about whether it can help in preventing or treating COVID-19, but it is not approved by any international association.
Our study aimed to evaluate and analyze the incidence of COVID-19 in patients with SLE, RA, SS and, MCTD who were taking Hydroxychloroquine for their rheumatic diseases.
This was a prospective study that included 145 patients with SLE, RA, SS, and MCTD who were on HCQ. The study began on 25/02/2020 (14 days before discovering the first cases of SARS-Cov2 in Albania) and was completed on 25 March 2021, coinciding with the start of massive vaccination. All patients were completed with SARS-Cov-2 serology and PCR.
After analyzing the data, it was seen that in 24 patients(16.6%) were found positive IgG anti-Cov-2, 4 patients had experienced pulmonary complications, however, not requiring hospitalization. Twelve of them had RA, 3 had SS, 7 patients had SLE and 2 patients had MCTD. All IgG-positive patients had taken 200mg/day. The other 121 patients(83.4%) were found to have negative IgG anti-Cov-2 antibodies.
Our study resulted in a low incidence of COVID-19 in patients with rheumatic diseases on hydroxychloroquine. This suggests a protective role of this drug in rheumatic patients, even in moderate usual doses.