Absence of autoantibodies against correctly folded recombinant fibrillin-1 protein in systemic sclerosis patients.

Jürgen Brinckmann, Nico Hunzelmann, Ehab El-Hallous, Thomas Krieg, Lynn Y. Sakai, Sven Krengel, Dieter P. Reinhardt

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Autoantibodies against short recombinant fragments of fibrillin-1 produced in bacterial expression systems have been found in tight-skin mouse, systemic sclerosis, mixed connective tissue disease, and primary pulmonary hypertension syndrome. In patients with scleroderma, the frequency of anti-fibrillin-1 antibodies was 42% in Caucasians. Until now it has been unclear whether this immune response has a primary function in disease pathogenesis or is a secondary phenomenon. In the present study we analyzed the frequency of autoantibodies against two overlapping recombinant polypeptides spanning the N-terminal and C-terminal halves of human fibrillin-1, which were produced in human embryonic kidney (HEK-293) cells. Correct three-dimensional structures of the recombinant fibrillin-1 polypeptides were shown by electron microscopy and immunoreactivity with antibodies. Screening of fibrillin-1 antibodies was performed in 41 sera from systemic sclerosis patients and in 44 healthy controls with a Caucasian background. Microtiter plates were coated with the recombinant polypeptides of fibrillin-1 and incubated with 1:100 diluted sera. Positive binding was defined as being more than 2 SD above the mean of the control group. ELISAs showed that none of the sera of patients with systemic sclerosis contained autoantibodies against the N-terminal or C-terminal recombinant fibrillin-1 polypeptide. The data show the absence of autoantibodies against recombinant fibrillin-1 protein in Caucasian systemic sclerosis patients. Because the correct three-dimensional folding of the recombinant proteins has been substantiated by several independent methods, we conclude that autoantibodies against correctly folded fibrillin are not a primary phenomenon in the pathogenesis of systemic sclerosis.

Original languageEnglish (US)
Pages (from-to)R1221-1226
JournalArthritis research & therapy
Volume7
Issue number6
StatePublished - 2005

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

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    Brinckmann, J., Hunzelmann, N., El-Hallous, E., Krieg, T., Sakai, L. Y., Krengel, S., & Reinhardt, D. P. (2005). Absence of autoantibodies against correctly folded recombinant fibrillin-1 protein in systemic sclerosis patients. Arthritis research & therapy, 7(6), R1221-1226.