Immunoglobulin subclass levels in patients with non‐Hodgkin lymphoma

Abstract

Allergy/atopy has been suggested to protect against non-Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG 4 in 200 NHL patients and 200 age-and sexmatched controls. Patients with B-cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10-15% of B-cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG 4 and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B-cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B-cell NHL types. Low immunoglobulin levels appear to be a consequence of B-cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B-cell NHL. ' 2008 Wiley-Liss, Inc.Key words: diffuse large B-cell NHL; follicular NHL; mantle cell NHL; Denmark; Sweden; stage; treatment; co-stimulation; CD80; CD86; B7-1; B7-2 Non-Hodgkin lymphoma (NHL) is a malignancy of the immune system but its relationship to immunity is complex. A prominent observation is that NHL incidence has been increasing steadily over the past several decades in the developed countries, 1 starting long before the abrupt increases of high grade lymphoma seen in association with the AIDS epidemic. 2 For the non-AIDS-related NHL types, this trend continued in the United States at least through 1998. 2 In Scandinavia, similar increases were observed into the early 1990s, but rates have stabilized in the past decade. 3 Some investigators proposed to explain this increase by a 'hygieneÕ hypothesis, which postulated that the impact of delaying a common infection might be responsible for increasing lymphoma risk, 4,5 but other explanations are plausible. It may be that, when naturally occurring mutations accumulate in undifferentiated, replicate-competent cells, lymphoma becomes more common. 6 A corollary to the hygiene hypothesis is that allergic/atopic conditions are becoming more common in the population. [7][8][9][10] Chronic immunologic stimulation by allergens may serve to differentiate the immune system. Many studies have attempted to correlate allergy/atopy history with risk of lymphoma, with conflicting results. 11-17 However, allergy/atopy represents a range of diverse conditions, ranging from hay fever and asthma to drug reactions. Furthermore, these conditions vary greatly in severity and hence in their recognition and reporting. These variations may lead to different immune impacts. Nevertheless, on balance, the evidence seems to favor lower l...

IgA and IgG hypogammaglobulinemia in Waldenstrom's macroglobulinemia

“…The incidence of IgA, IgG, or both IgA and IgG hypogammaglobulinemia in this series of 207 untreated WM patients was 63.3%, 58.0% and 49.3%, respectively, which is similar to the incidence reported among patients with chronic lymphocytic leukemia, 6,7 but higher than that reported in other indolent lymphomas in which the incidence of IgA and IgG hypogammaglobulinemia ranges from 10-20%. 7 The incidence of IgA and/or IgG hypogammaglobulinemia observed in this study also appears to be higher than that observed in individuals with IgM monoclonal gammopathy of unknown significance (MGUS), although there is great variation in the reported incidences in this latter conidtion (8-35%). 15,16 The inclusion of patients with up to 10% bone marrow disease involvement, who are now considered to have WM based on consensus diagnostic criteria, may account for the higher incidence of IgA and/or IgG hypogammaglobulinemia observed in the series reported by Kyle et The presence of IgA and/or IgG hypogammaglobulinemia was reported to predict for evolution of IgM MGUS to WM in the series of patients studied by Kyle et al 16 While the presence of IgA and IgG hypogammaglobulinemia per se was not associated with disease progression, WM patients in this series who were initially managed with a 'watch and wait' strategy but whose disease ultimately progressed had lower median IgA and IgG levels.…”

“…5 The presence of hypogammaglobulinemia of the 'uninvolved' immunoglobulin has also been reported among other B-cell malignancies. 6,7 The etiology of this finding remains unclear, but has been speculated to be based on tumor-induced immunoparesis and host-mediated homeostatic regulation of 'uninvolved' immunoglobulin production.…”

Impact of Selenium Supplementation in Neutropenia and Immunoglobulin Production in Childhood Cancer Patients

“…[45][46][47] The inverse association between IgE production levels and risk for developing diseases, such as leukemia, lymphoma, glioma, pancreatic cancer, among others, has been extensively evaluated. [48][49][50][51][52][53] Jensem-Jarolin et al 45 showed that, in conditions where serum IgE are directed against tumor-associated antigens, these immunoglobulins could be considered as mediators of cell-cell contact where the tumor cell would be recognized by the immune effector cell resulting in an immune synapse known as antibody-dependent cytotoxicity (ADCC).…”

Serum immunoglobulin levels in patients with lymphoproliferative diseases in Erbil, Kurdistan region, Iraq

“…32,33 IgG levels were not decreased in one study, 32 but in contrast, it was decreased in other studies, 33 while a study 34 showed no increase in IgG levels, and lower IgG levels in NHL patients was observed. 33,34 Levels of all immunoglobulin class were decreased in NHL patients. Another study which supports our results demonstrated that the most frequent hypoimmunoglobulinaemia is in class IgM (22%), followed by IgA (8%).…”

“…Another study which supports our results demonstrated that the most frequent hypoimmunoglobulinaemia is in class IgM (22%), followed by IgA (8%). 35,36 In NHL patients intrinsic B-cell defects, increased T-cell or monocyte suppressor activity, and diminished T-helper activity m a y a l s o c o n t r i b u t e t o t h e hypogammaglobulinaemia. [37][38][39] One of ten studied patients with NHL had an M band, this has been reported by other worker.…”