Defective antibody formation is the main phenotypic feature in the majority of primary immunodeficiency diseases, with common variable immunodeficiency (CVID) as the most common clinically severe form of primary immunodeficiency. In addition to susceptibility to infections CVID patients show non-infectious disease manifestations such as B cell lymphoma.
We measured serum immunoglobulins, IgG subclasses, IgG- and –IgM-antibodies against T-dependent and T-independent, bacterial, viral and vaccination antigens, lymphocyte subsets including B cell subsets and lymphoproliferative responses in patients in whom susceptibility to infections developed after or during treatment for B cell malignancy.
Upon diagnosis of CVID all ten patients presented with undue susceptibility to infections which normalized upon initiation of immunoglobulin replacement therapy. The median delay between the diagnosis of lymphoid malignancy as the first clinical manifestation and the diagnosis of CVID was 5 years (range 0.5 to 19 years). The decrease in serum IgG in these patients was variable (range 42 – 671 mg/dl), but an impaired IgG response to vaccination against tetanus, diphtheria or TBEV and a decreased IgG antibody responses against ubiquitous microbial antigens [staphylococcal and streptococcal toxins, bacterial polysaccharides, viral antigens such as MMR and VZV] confirmed the diagnosis of CVID and thus the need to initiate long-term immunoglobulin replacement therapy.
Our findings indicate that immunological examination of patients with hematological malignancy, in particular B cell tumors, should be mandatory at diagnosis and during follow-up in order to achieve early diagnosis and treatment of clinically relevant antibody deficiency such as CVID.