Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies?
Abstract Background The 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 survi...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-06-01
|
| Series: | BMC Immunology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12865-017-0217-9 |
| _version_ | 1818929816579080192 |
|---|---|
| author | Marian-Christopher Pott Natalie Frede Jennifer Wanders Lennart Hammarström Erik-Oliver Glocker Cristina Glocker Fariba Tahami Bodo Grimbacher |
| author_facet | Marian-Christopher Pott Natalie Frede Jennifer Wanders Lennart Hammarström Erik-Oliver Glocker Cristina Glocker Fariba Tahami Bodo Grimbacher |
| author_sort | Marian-Christopher Pott |
| collection | DOAJ |
| description | Abstract Background The 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). Results Two 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. Conclusion Whilst 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. |
| first_indexed | 2024-12-20T03:50:49Z |
| format | Article |
| id | doaj.art-b7fa29ed94d2478f833bb2414e405a9e |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-20T03:50:49Z |
| publishDate | 2017-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-b7fa29ed94d2478f833bb2414e405a9e2022-12-21T19:54:29ZengBMCBMC Immunology1471-21722017-06-011811810.1186/s12865-017-0217-9Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies?Marian-Christopher Pott0Natalie Frede1Jennifer Wanders2Lennart Hammarström3Erik-Oliver Glocker4Cristina Glocker5Fariba Tahami6Bodo Grimbacher7Centre for Chronic Immunodeficiency, Medical Centre University Hospital, Medical Faculty of FreiburgCentre for Chronic Immunodeficiency, Medical Centre University Hospital, Medical Faculty of FreiburgInstitute of Immunity and Transplantation, Royal Free Hospital, University College LondonDepartment of Immunology, Karolinska InstitutetInstitute of Medical Microbiology and Hygiene, University Medical Center FreiburgCentre for Chronic Immunodeficiency, Medical Centre University Hospital, Medical Faculty of FreiburgInstitute of Immunity and Transplantation, Royal Free Hospital, University College LondonCentre for Chronic Immunodeficiency, Medical Centre University Hospital, Medical Faculty of FreiburgAbstract Background The 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). Results Two 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. Conclusion Whilst 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.http://link.springer.com/article/10.1186/s12865-017-0217-9AutoimmunityAutoantibodiesCytokinesPrimary antibody deficiencyCommon variable immunodeficiencySelective IgA deficiency |
| spellingShingle | Marian-Christopher Pott Natalie Frede Jennifer Wanders Lennart Hammarström Erik-Oliver Glocker Cristina Glocker Fariba Tahami Bodo Grimbacher Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies? BMC Immunology Autoimmunity Autoantibodies Cytokines Primary antibody deficiency Common variable immunodeficiency Selective IgA deficiency |
| title | Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies? |
| title_full | Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies? |
| title_fullStr | Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies? |
| title_full_unstemmed | Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies? |
| title_short | Autoantibodies against BAFF, APRIL or IL21 - an alternative pathogenesis for antibody-deficiencies? |
| title_sort | autoantibodies against baff april or il21 an alternative pathogenesis for antibody deficiencies |
| topic | Autoimmunity Autoantibodies Cytokines Primary antibody deficiency Common variable immunodeficiency Selective IgA deficiency |
| url | http://link.springer.com/article/10.1186/s12865-017-0217-9 |
| work_keys_str_mv | AT marianchristopherpott autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies AT nataliefrede autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies AT jenniferwanders autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies AT lennarthammarstrom autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies AT erikoliverglocker autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies AT cristinaglocker autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies AT faribatahami autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies AT bodogrimbacher autoantibodiesagainstbaffapriloril21analternativepathogenesisforantibodydeficiencies |