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Murine studies suggest that complement modulates helper T\u2010cell differentiation, and Th1 responses in particular are impaired in the absence of functional complement. Here, we have studied humoral responses to toxoid vaccines in eight patients with C3 deficiency, representing more than 25% of all the known patients worldwide. Serum cytokine levels were also studied. The patients developed normal Ig responses to tetanus and diphtheria toxoids, but IgE levels were low. The pattern of antigen\u2010specific IgG subclasses was abnormal, with increased Th1\u2010related IgG3 responses, low IgG2, and almost completely undetectable IgG4. The patients also had increased amounts of Th1\u2010related cytokines IL\u201012p70 and IL\u201021, and these showed a positive correlation with IgG3 levels. Our results confirm that complement modulates Th differentiation, but reveal a more nuanced outcome than previously reported. Since IgG4 has been linked to tolerogenic responses, the data also suggest that in the absence of functional complement at least some aspects of systemic tolerance are impaired.<\/jats:p>","DOI":"10.1002\/eji.201444948","type":"journal-article","created":{"date-parts":[[2014,11,29]],"date-time":"2014-11-29T09:39:55Z","timestamp":1417253995000},"page":"915-921","source":"Crossref","is-referenced-by-count":19,"title":["Dysregulation of adaptive immune responses in complement C3\u2010deficient patients"],"prefix":"10.1002","volume":"45","author":[{"given":"Pirkka T.","family":"Pekkarinen","sequence":"first","affiliation":[{"name":"Haartman Institute and Research Programs Unit Immunobiology University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelli","family":"Heikkil\u00e4","sequence":"additional","affiliation":[{"name":"Haartman Institute and Research Programs Unit Immunobiology University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Kisand","sequence":"additional","affiliation":[{"name":"Molecular Pathology Institute of Biomedicine and Translational Medicine University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4rt","family":"Peterson","sequence":"additional","affiliation":[{"name":"Molecular Pathology Institute of Biomedicine and Translational Medicine University of Tartu  Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Botto","sequence":"additional","affiliation":[{"name":"Centre for Complement and Inflammation Research Division of Immunology and Inflammation Department of Medicine Imperial College  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed R.","family":"Daha","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center and University Medical Center  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Drouet","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Joseph Fourier GREPI\/AGIM CNRS FRE3405  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lourdes","family":"Isaac","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merja","family":"Helminen","sequence":"additional","affiliation":[{"name":"The Paediatric Research Centre Tampere University and University Hospital  Tampere"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tari","family":"Haahtela","sequence":"additional","affiliation":[{"name":"Department of Allergy Skin and Allergy Hospital Helsinki University Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seppo","family":"Meri","sequence":"additional","affiliation":[{"name":"Haartman Institute and Research Programs Unit Immunobiology University of Helsinki  Helsinki Finland"},{"name":"HUSLAB and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Jarva","sequence":"additional","affiliation":[{"name":"Haartman Institute and Research Programs Unit Immunobiology University of Helsinki  Helsinki Finland"},{"name":"HUSLAB and Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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