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Comprehensive Longitudinal Surveillance of the IgG Autoantibody Repertoire in Established Systemic Lupus Erythematosus
Author(s) -
Vordenbäumen Stefan,
Brinks Ralph,
Hoyer Annika,
FischerBetz Rebecca,
Pongratz Georg,
Lowin Torsten,
Zucht HansDieter,
Budde Petra,
Bleck Ellen,
SchulzKnappe Peter,
Schneider Matthias
Publication year - 2019
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.40788
Subject(s) - autoantibody , epitope , immunology , lupus nephritis , antibody , medicine , epitope mapping , systemic lupus erythematosus , antigen , lupus erythematosus , connective tissue disease , recombinant dna , autoimmune disease , biology , genetics , gene , disease
Objective To investigate the role of epitope spreading in established systemic lupus erythematosus ( SLE ). Methods IgG autoantibody reactivity with 398 distinct recombinant proteins was measured over a period of 6 years in 69 SLE patients and compared to that in 45 controls. Changes in mean fluorescence intensity ( MFI ), number of autoantibodies to distinct antigens, and reactivity with distinct clones of established antigenic targets (e.g., U1 RNP , Sm, and ribosomal P) representing epitope fine mapping were assessed. Linear mixed modeling, adjusted with Bonferroni correction for age and sex, was applied. Results The total number of autoantibodies, mean MFI , and number of autoantibodies in epitope fine mapping were higher in SLE patients compared to controls ( P < 0.0001). The total number of antibodies to distinct autoantigens remained stable over time, while the mean MFI decreased over time in SLE ( P < 0.021). SLE patients showed variable recognition of epitopes in fine mapping over time. In particular, in SLE patients, more clones of the U1 RNP complex were recognized at the time of new organ involvement (+0.65) ( P = 0.007). Mean MFI was higher in patients with lupus nephritis ( P = 0.047). The time‐averaged MFI s of 22 individual autoantibodies (including double‐stranded DNA [ds DNA ]) were higher, after Bonferroni correction, in SLE ( P < 0.0001). The MFI s of ds DNA and histone cluster 2 H3c were associated with scores on the Systemic Lupus Activity Measure ( P < 0.0001). Conclusion Longitudinal surveillance of the IgG autoantibody repertoire in established SLE reveals evidence of sustained breadth of autoantibody repertoire without significant expansion. Associations of disease activity with ds DNA and with histone H3 autoantibodies were confirmed.