PIK3CD GOF patients have autoreactive serum antibodies. (A) Heatmap showing relative binding of serum IgM from healthy controls (Ctrl; n = 2), PIK3CD GOF (n = 12), or SLE (n = 2) patients to different self-antigens. Shown are antibodies with statistical difference as detected by significance analysis of microarray test. ssDNA, single-stranded DNA. (B and C) Measurement of serum VH4-34 autoantibodies against I/i blood group carbohydrates on the surface of transitional B cells. Serum from PIK3CD GOF patients or healthy controls was incubated with peripheral blood mononuclear cells from healthy controls (HC), and serum VH4-34 antibodies that bound to transitional B cells were then detected with the 9G4 anti-idiotypic monoclonal antibody, which binds unmutated VH4-34. Each point represents an individual patient (n = 5) or healthy control (n = 24) combined from four separate experiments; line gives geometric mean and SD. Significant differences were determined by Mann-Whitney test. ***, P < 0.001. See also Fig. S1.