Anti-CD20
therapy is effective in idiopathic
nephrotic syndrome (INS). However, transient or sustained
hypogammaglobulinemia predisposing to an increased risk of
infectious diseases can follow treatment in some patients. We analyzed the long-term effects of anti-CD20
therapy on immunological memory in 27 frequently-relapsing/
steroid-dependent INS pediatric patients after more than 4 years from the first and at least 2 years from the last anti-CD20 infusion. Twenty-one INS children, never treated with anti-CD20 and under an intense oral immunosuppression with
prednisone,
mycophenolate mofetil, and
calcineurin inhibitors were also included as control group. Levels of circulating B-cell subpopulations, total serum
immunoglobulins and
IgG and memory B cells directed against hepatitis B virus (HBV) and
tetanus were determined and correlated with clinical characteristics. Nine patients never relapsed after more than 2 years from the last anti-CD20 administration (5 after the first, 3 after the second, and 1 after the fifth infusion). At last follow-up, most patients showed a complete recovery and normalization of total (27/27), transitional (27/27), and mature-naïve B cells (25/27). However, a sustained and significant reduction of total memory (20/27) and switched memory (21/27) B cells was found in most patients. 11/27 patients showed
hypogammaglobulinemia at last follow-up and, among these, four presented with a severe
hypogammaglobulinemia (
IgG < 160 mg/dl). In contrast, no patient in the control group developed a severe
hypogammaglobulinemia. Age at the time of first anti-CD20 administration was positively associated with
IgG levels at last follow-up (p = 0.008); accordingly, younger patients had an increased risk of
hypogammaglobulinemia (p = 0.006). Furthermore, severe
hypogammaglobulinemia and delayed switched memory B-cell reconstitution were more frequent in non-relapsing patients. Reduced
IgG levels against HBV and
tetanus were observed at baseline and further declined at last follow-up.
Antigen-specific memory B-cells were induced by re-immunization, but specific
IgG titers remained low. In conclusion, anti-CD20
therapy can be disease-modifying in some INS patients. However, a prolonged impairment of immunological memory occurs frequently, independently from the number of anti-CD20 infusions, particularly in younger patients. Re-immunization may be necessary in these patients.