An Older Gentleman with Common Variable Immunodeficiency (CVID): A Question of Primary Immunodeficiency Versus Secondary Belimumab-Induced Immunodeficiency

Rationale: CVID is the most common symptomatic primary immunodeficiency, with perhaps 5% presenting with inflammatory or autoimmune disease without recurrent infection.  We present a case of CVID diagnosed subsequent to limited treatment of systemic lupus erythematosus (SLE) and suggest that belimumab, a monoclonal antibody that binds to B-cell activating factor (BLyS), inhibiting B-cell stimulation, accelerated the presentation of immunodeficiency in this patient.

Methods: A retrospective chart review was performed of a patient who received 2 doses of belimumab, for SLE poorly responsive to anti-malarial and corticosteroid treatment, which was discontinued due to development of acute pancreatitis. An immune evaluation 2 years after receiving the BLyS-specific inhibitor, fulfilled diagnostic criteria for CVID and immunoglobulin replacement was initiated.

Results: Two years after limited treatment with a humoral immunomodulator, an evaluation due to continued severe symptoms, without reported recurrent infections, revealed hypogammaglobulinemia, and sub-protective levels of pneumococcal and tetanus antibodies. Immune evaluation prior to therapy was not conducted, complicating the diagnosis of CVID as delayed diagnosis versus a secondary immunodeficiency.

Conclusions: Although a small extension of a phase II study of belimumab demonstrated modest decrease in memory B cells and plasma cells, the possibility of provoked B-cell dysfunction exists. A case series identifying 11 patients with secondary rituximab-induced immunodeficiency, long after discontinuation of the anti-CD20 antibody, supports this supposition.  As the utilization of immunomodulatory therapy increases, it will be important to perform baseline serum immunoglobulin levels and B cell population analysis prior to starting B-cell specific biologic therapies.