Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies?

BMC Immunology

Research Article

Marian-Christopher Pott¹  Natalie Frede¹  Cristina Glocker¹  Bodo Grimbacher²  Lennart Hammarström³  Jennifer Wanders⁴  Fariba Tahami⁴  Erik-Oliver Glocker⁵ 

[1] Centre for Chronic Immunodeficiency, Medical Centre University Hospital, Medical Faculty of Freiburg, Freiburg, Germany;Centre for Chronic Immunodeficiency, Medical Centre University Hospital, Medical Faculty of Freiburg, Freiburg, Germany;Institute of Immunity and Transplantation, Royal Free Hospital, University College London, London, UK;Department of Immunology, Karolinska Institutet, Stockholm, Sweden;Institute of Immunity and Transplantation, Royal Free Hospital, University College London, London, UK;Institute of Medical Microbiology and Hygiene, University Medical Center Freiburg, Freiburg, Germany;Institute of Laboratory Medicine, Brandenburg Hospital, Brandenburg Medical School, Brandenburg, Germany;

关键词: Autoimmunity;    Autoantibodies;    Cytokines;    Primary antibody deficiency;    Common variable immunodeficiency;    Selective IgA deficiency;    BAFF;    APRIL;    IL-21;   

DOI  :  10.1186/s12865-017-0217-9

 received in 2016-10-30, accepted in 2017-06-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe ability of anti-cytokine antibodies to play a disease-causing role in the pathogenesis of immunodeficiencies is widely accepted. The aim of this study was to investigate whether autoantibodies against BAFF (important B cell survival signal), APRIL (important plasma cell survival signal), or Interleukin-21 (important cytokine for immunoglobulin class switch) present an alternative mechanism for the development of the following primary antibody deficiencies (PADs): common variable immune deficiency (CVID) or selective IgA deficiency (sIgAD).ResultsTwo hundred thirty-two sera from patients with PADs were screened for autoantibodies against cytokines by ELISA. Statistical data analysis yielded a significant difference (p < 0.01) between the healthy donor sera and both PAD cohorts. The analysis was deepened by subdividing the patient collective into groups with distinct B cell phenotypes but no significant differences were found. For selected sera with notable high ELISA-read outs functional analysis ensued. Anti-BAFF and anti-APRIL antibodies were further examined by a B cell survival assay, whilst the functional relevance of putative anti-IL-21 autoantibodies was investigated by means of a STAT3 phosphorylation assay. However, the results of these experiments revealed no discernible functional effect.ConclusionWhilst statistical analysis of ELISA results showed significant differences between patients and healthy controls, in our set of patients functional tests yielded no evidence for an involvement of autoantibodies against BAFF, APRIL, or IL-21 in the pathogenesis of CVID or sIgAD.

【 授权许可】

CC BY   
© The Author(s). 2017