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.