Dysregulation of adaptive immune responses in complement C3-deficient patients

Pirkka T. Pekkarinen*, Nelli Heikkila, Kai Kisand, Paert Peterson, Marina Botto, Mohamed R. Daha, Christian Drouet, Lourdes Isaac, Merja Helminen, Tari Haahtela, Seppo Meri, Hanna Jarva, T. Petteri Arstila

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    9 Citations (Scopus)


    In addition to its effector functions, complement is an important regulator of adaptive immune responses. Murine studies suggest that complement modulates helper T-cell 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-specific IgG subclasses was abnormal, with increased Th1-related IgG3 responses, low IgG2, and almost completely undetectable IgG4. The patients also had increased amounts of Th1-related cytokines IL-12p70 and IL-21, 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.

    Original languageEnglish
    Pages (from-to)915-921
    Number of pages7
    JournalEuropean Journal of Immunology
    Issue number3
    Publication statusPublished - Mar-2015


    • Adaptive immunity
    • Complement
    • Immune deficiency
    • Immunoglobulin G subclass
    • Immunoglobulin G4
    • T-CELLS
    • IGG4
    • IL-10

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