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Papers of the Week

Papers: 14 May 2022 - 20 May 2022

Pharmacology/Drug Development

2022 May


36 Suppl 1

On the Flame: The Fab Fragment of Rheumatoid Arthritis.


Chen K, Akintola T, Lawrence K, Lane J
FASEB J. 2022 May; 36 Suppl 1.
PMID: 35556532.


With more than 200,000 cases per year, Rheumatoid Arthritis (RA) is one of the most common autoimmune disorders in the United States. Across the globe, up to 14 million people are affected by its symptoms of joint pain, stiffness, swelling, fatigue, and even physical deformity. Rheumatoid factors (RF) are autoantibodies that correlate with RA severity and recognize epitopes in the Fc region of its antigen immunoglobulin (Ig) G, yet it is paradoxically found circulating in the blood alongside the antigen without binding to it. According to Thomsen, et. al, a 2018 study that contested the idea of IgG aggravation as the prerequisite to RF binding, the native state of IgG is present in a closed form, where the Fab fragment shields the Fc region, only exposing the Fc effector sites when a conformational change is induced. This closed form is a result of a missing galactose between the C□2 domains of the heavy chains, thus causing the IgG to self associate, forming immune complexes to fix the complement system. The subsequent heightened inflammatory response exacerbates the progression of joint damage in RA and other severe symptoms. In this study, we examined RF in relation to IgG forming immune complexes to achieve a better understanding of the immunological progression or pathogenesis of RA. The Mahtomedi MSOE Center for BioMolecular Modeling MAPS Team used 3-D modeling and printing technology to examine structure-function relationships of Fab and Fc fragments in IgG. The visual model will be a valuable tool in developing our story.