OBJECTIVE: Autoantibody production in patients with systemic lupus erythematosus (SLE) is associated with abnormalities of B cell function and phenotype. Clinical responses to B cell depletion therapy (BCDT), based on rituximab, are encouraging. Therefore, we undertook this study to investigate the effect of BCDT on antibody profiles. METHODS: Serial sera from 16 patients with active, refractory SLE were assayed for antinucleosome antibodies, anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigen, anti-tetanus toxoid, and antibodies to pneumococcal capsular polysaccharide for at least 1 year following BCDT. Anti-dsDNA antibodies derived from the V(H)4.34 immunoglobulin germ line gene (9G4+) were also measured. RESULTS: All patients achieved peripheral B cell depletion and improved clinically for at least 3 months. Antinucleosome and anti-dsDNA antibodies decreased to a mean +/- SD of 64 +/- 37% and 38 +/- 33% of baseline values, respectively, by 6-8 months post-BCDT. Levels of other autoantibodies and antimicrobial antibodies were generally unchanged. In the 9 of 16 patients who were still well at 1 year, anti-dsDNA antibodies fell to 42 +/- 36% of baseline values at 6-8 months and to 37 +/- 33% at 10-14 months. In patients who had disease flares within 1 year of BCDT, levels of these antibodies decreased to 60 +/- 40% and 83 +/- 93% of baseline values at 6-8 months and at 10-14 months, respectively. Circulating anti-dsDNA antibodies were positive for 9G4 expression in 4 of 6 patients tested, and flares in 2 of these patients were accompanied by rises in 9G4+ anti-dsDNA antibodies. CONCLUSION: These observations suggest that B cell clones committed to producing antinucleosome and anti-dsDNA antibodies, including the V(H)4.34 subpopulation of anti-dsDNA antibodies, have a relatively rapid turnover compared with B cell clones producing other antibodies. There was also a trend toward a greater and more sustained decrease in anti-dsDNA antibodies in patients with clinical benefit lasting >1 year.
OBJECTIVE: Autoantibody production in patients with systemic lupus erythematosus (SLE) is associated with abnormalities of B cell function and phenotype. Clinical responses to B cell depletion therapy (BCDT), based on rituximab, are encouraging. Therefore, we undertook this study to investigate the effect of BCDT on antibody profiles. METHODS: Serial sera from 16 patients with active, refractory SLE were assayed for antinucleosome antibodies, anti-double-stranded DNA (anti-dsDNA), anti-extractable nuclear antigen, anti-tetanus toxoid, and antibodies to pneumococcal capsular polysaccharide for at least 1 year following BCDT. Anti-dsDNA antibodies derived from the V(H)4.34 immunoglobulin germ line gene (9G4+) were also measured. RESULTS: All patients achieved peripheral B cell depletion and improved clinically for at least 3 months. Antinucleosome and anti-dsDNA antibodies decreased to a mean +/- SD of 64 +/- 37% and 38 +/- 33% of baseline values, respectively, by 6-8 months post-BCDT. Levels of other autoantibodies and antimicrobial antibodies were generally unchanged. In the 9 of 16 patients who were still well at 1 year, anti-dsDNA antibodies fell to 42 +/- 36% of baseline values at 6-8 months and to 37 +/- 33% at 10-14 months. In patients who had disease flares within 1 year of BCDT, levels of these antibodies decreased to 60 +/- 40% and 83 +/- 93% of baseline values at 6-8 months and at 10-14 months, respectively. Circulating anti-dsDNA antibodies were positive for 9G4 expression in 4 of 6 patients tested, and flares in 2 of these patients were accompanied by rises in 9G4+ anti-dsDNA antibodies. CONCLUSION: These observations suggest that B cell clones committed to producing antinucleosome and anti-dsDNA antibodies, including the V(H)4.34 subpopulation of anti-dsDNA antibodies, have a relatively rapid turnover compared with B cell clones producing other antibodies. There was also a trend toward a greater and more sustained decrease in anti-dsDNA antibodies in patients with clinical benefit lasting >1 year.
Authors: Tanvi Arkatkar; Holly M Jacobs; Samuel W Du; Quan-Zhen Li; Kelly L Hudkins; Charles E Alpers; David J Rawlings; Shaun W Jackson Journal: Kidney Int Date: 2018-06-12 Impact factor: 10.612
Authors: Jolan E Walter; Francesca Rucci; Laura Patrizi; Mike Recher; Stephan Regenass; Tiziana Paganini; Marton Keszei; Itai Pessach; Philipp A Lang; Pietro Luigi Poliani; Silvia Giliani; Waleed Al-Herz; Morton J Cowan; Jennifer M Puck; Jack Bleesing; Tim Niehues; Catharina Schuetz; Harry Malech; Suk See DeRavin; Fabio Facchetti; Andrew R Gennery; Emma Andersson; Naynesh R Kamani; JoAnn Sekiguchi; Hamid M Alenezi; Javier Chinen; Ghassan Dbaibo; Gehad ElGhazali; Adriano Fontana; Srdjan Pasic; Cynthia Detre; Cox Terhorst; Frederick W Alt; Luigi D Notarangelo Journal: J Exp Med Date: 2010-06-14 Impact factor: 14.307