Introduction
Recurrent bacterial, viral, fungal and/or parasitic infections are the hallmark events of primary and secondary immunodeficiencies. The most common forms of primary immunodeficiencies (PIDs) are related to inherited adaptive immune system dysfunctions that involve B and/or T cells not unfrequently discovered in adulthood. For secondary immunodeficiencies (SIDs), the main causes correspond to chemotherapy or immunosuppressant use or are related to underlying diseases such as cancers, lymphomas, and systemic inflammatory/autoimmune diseases. Other causes and mechanisms of SIDs proceed from protein wasting or metabolic disorders, including severe general state impairment.
In addition to infections, other events, such as autoimmune cytopenias, cancers or lymphoproliferative disorders, including diffuse large B cell lymphoma (DLBCL), can complicate the natural history of PIDs.(1–3) The most frequent subtype, common variable immunodeficiency (CVID), renders affected patients more prone to developing lymphomas(4–7) and mostly frequent infections identified as the main feature, responsible for diagnosis and main cause of death in this population.(2,8,9) The diagnosis of PIDs is often delayed for several years, because of their clinical heterogeneity and the higher frequency of banal and neglected infections. In this context, both the onset date and natural history of the different complications of PIDs, such as malignant events, remain little known.
We therefore hypothesized that DLBCL with a datable diagnosis might also reveal PIDs with possible previous infectious events that had not led to the recognition of a PID. No study has yet determined the prevalence of PIDs in adults revealed by lymphoma since the diagnostic criteria of PIDs do not take into account lymphoma.(10–15) On the one hand, humoral PIDs, including CVID, are frequent forms of PIDs and can be easily be suggested by low serum total gamma-globulin level identified using serum electrophoresis (SEP) performed at DLBCL diagnosis. On the other hand, DLBCL, the most frequent of lymphoproliferative disorders, can also induce a decrease in serum total gamma-globulin level (TGL) because of clonal selection and proliferation. However, the frequency, the risk and prognosis of infectious events related to L-TGL discovered at DLBCL diagnosis are unknown and no specific therapeutic strategy is therefore recommended in this context. Meanwhile, in the context of multiple myeloma or chronic lymphoid leukemia, the lowest (L)-TGL are well recognized to correspond to an SID with a documented increased infectious events and risk that therefore requires polyvalent immunoglobulin infusions.(16–19)
The clinical relevance and utility of SEP performance for L-TGL research in DLBCL is unknown, both at diagnosis and during the therapeutic follow-up of the lymphoproliferative disorder. Moreover, the association of SEP and DLBCL is of particular interest, as SEP can be easily and routinely performed at DLBCL diagnosis, in order to at least assess the functionality of the B cell compartment and because DLBCL onset, unlike the onset of indolent lymphomas, can easily be dated based on B symptoms and rapid tumoral syndrome.
Herein, we conducted a retrospective study to assess the clinical and prognostic relevance of L-TGL discovery at DLBCL diagnosis in Caen Tertiary Hospital. Our main judgment criteria were the frequency of L-TGL in comparison to H-TGL at DLBCL diagnosis, the mortality rates and main causes of death, especially those related to infectious events among subgroups.