Immune-Related and Inflammatory Conditions
Immune-Related and Inflammatory Conditions
Background Chronic immune stimulation appears to be associated with lymphoplasmacytic lymphoma (LPL)-Waldenström macroglobulinemia (WM); however, available information is sparse. We conducted, to our knowledge, the most comprehensive study to date to evaluate associations between a personal or family history of many immune-related and/or inflammatory disorders and the subsequent risk of LPL-WM.
Methods We used Swedish population-based registries to identify 2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 first-degree relatives of either case patients or control subjects. We evaluated a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each condition by use of logistic regression.
Results An increased risk of LPL-WM was associated with a personal history of the following autoimmune diseases: systemic sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjögren syndrome (OR = 12.1, 95% CI = 3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2), polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis (OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95% CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR = 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 5.0). An increased risk of LPL-WM was associated with a family history of the following autoimmune or infectious diseases: Sjögren syndrome (OR = 5.0, 95% CI = 2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2), Guillain–Barré syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR = 2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3 to 2.7), and chronic prostatitis (OR = 4.3, 95% CI = 1.7 to 11.1).
Conclusions Personal history of certain immune-related and/or infectious conditions was strongly associated with increased risk of LPL-WM. The association of both personal and family history of Sjögren syndrome and autoimmune hemolytic anemia with risk of LPL-WM indicates the potential for shared susceptibility for these conditions.
Lymphoplasmacytic lymphoma (LPL)-Waldenström macroglobulinemia (WM) is a chronic lymphoproliferative tumor characterized by small B lymphocytes, plasmacytoid lymphocytes, and plasma cells and involves the bone marrow, lymph nodes, and spleen. The World Health Organization criteria for classification of hematological diseases list WM as a subset of LPL that is defined as LPL with bone marrow involvement and a detectable monoclonal IgM spike in serum. LPL-WM is a rare disease, with an annual incidence rate of three to four cases per million people. It is more common among the elderly, men, and white persons.
Although the etiology of LPL-WM is unknown, there are a few clues in the literature. For example, familial aggregation of WM was demonstrated in 1962. Since then, several studies of multiply affected families, case–control studies, and cohort studies have been published showing familial clustering of LPL and WM. Recently, we conducted a large population-based case–control study in Sweden and found that, compared with first-degree relatives of control subjects, first-degree relatives of LPL-WM patients have an increased risk for LPL-WM (odds ratio [OR] = 20, 95% confidence interval [CI] = 4.1 to 98.4), non-Hodgkin lymphoma (OR = 3.0, 95% CI = 2.0 to 4.4), chronic lymphocytic leukemia (OR = 3.4, 95% CI = 1.7 to 6.6), and monoclonal gammopathy of undetermined significance (OR = 5.0, 95% CI = 1.3 to 18.9). These findings support the hypothesis that there are shared common susceptibility genes that predispose individuals to LPL-WM and related lymphoproliferative disorders. Simultaneously, a few preclinical studies have reported evidence of somatic immunoglobulin gene mutations in WM, indicating a role for antigenic stimulation in the development of WM.
Because of the rarity of LPL-WM, only a few epidemiological studies have assessed the role of various types of chronic antigenic stimulatory conditions in relation to risk of developing LPL-WM, and their results have been conflicting. For example, a hospital-based study of 65 WM patients reported no association between a personal history of autoimmune disease and subsequent risk of developing WM. In contrast, two nationwide US veterans studies that included 361 and 165 WM patients, respectively, found increased risk of WM among individuals with a personal history of autoimmune disease, infection with hepatitis B and C virus or HIV, or rickettsiosis.
To increase understanding of the association between immune-related and/or inflammatory conditions and subsequent risk of LPL-WM, we conducted a large population-based case–control study by use of linked registry data from Sweden to examine the association between a personal history of various immune-related and/or inflammatory conditions and risk of LPL-WM. This study contained 2470 LPL-WM patients and 9698 matched control subjects. On the basis of previous observations that first-degree relatives of WM patients (compared with first-degree relatives of control subjects) might be more prone to developing various immunologic abnormalities and that immune and inflammatory genes might play a role in lymphomagenesis, we hypothesized that the association between immune-related and/or inflammatory conditions and risk of LPL-WM was modulated, to some degree, by polymorphisms in common genes that predisposed individuals to both types of conditions. If true, immune-related and/or inflammatory conditions and LPL-WM should aggregate in the same families. To test this hypothesis, we investigated 5710 first-degree relatives of case patients with LPL-WM and 22 799 first-degree relatives of control subjects to evaluate risk of LPL-WM among individuals with a family history of immune-related and/or inflammatory conditions.
Abstract and Introduction
Abstract
Background Chronic immune stimulation appears to be associated with lymphoplasmacytic lymphoma (LPL)-Waldenström macroglobulinemia (WM); however, available information is sparse. We conducted, to our knowledge, the most comprehensive study to date to evaluate associations between a personal or family history of many immune-related and/or inflammatory disorders and the subsequent risk of LPL-WM.
Methods We used Swedish population-based registries to identify 2470 case patients with LPL-WM, 9698 matched control subjects, and almost 30 000 first-degree relatives of either case patients or control subjects. We evaluated a wide range of autoimmune, infectious, allergic, and inflammatory conditions. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for each condition by use of logistic regression.
Results An increased risk of LPL-WM was associated with a personal history of the following autoimmune diseases: systemic sclerosis (OR = 4.7, 95% CI = 1.4 to 15.3), Sjögren syndrome (OR = 12.1, 95% CI = 3.3 to 45.0), autoimmune hemolytic anemia (OR = 24.2, 95% CI = 5.4 to 108.2), polymyalgia rheumatica (OR = 2.9, 95% CI = 1.6 to 5.2), and giant cell arteritis (OR = 8.3, 95% CI = 2.1 to 33.1). An increased risk of LPL-WM was associated with a personal history of the following infectious diseases: pneumonia (OR = 1.4, 95% CI = 1.1 to 1.7), septicemia (OR = 2.4, 95% CI = 1.2 to 4.3), pyelonephritis (OR = 1.7, 95% CI = 1.1 to 2.5), sinusitis (OR = 2.7, 95% CI = 1.4 to 4.9), herpes zoster (OR = 3.4, 95% CI = 2.0 to 5.6), and influenza (OR = 2.9, 95% CI = 1.7 to 5.0). An increased risk of LPL-WM was associated with a family history of the following autoimmune or infectious diseases: Sjögren syndrome (OR = 5.0, 95% CI = 2.1 to 12.0), autoimmune hemolytic anemia (OR = 3.8, 95% CI = 1.1 to 13.2), Guillain–Barré syndrome (OR = 4.1, 95% CI = 1.8 to 9.4), cytomegalovirus (OR = 2.7, 95% CI = 1.4 to 5.3), gingivitis and periodontitis (OR = 1.9, 95% CI = 1.3 to 2.7), and chronic prostatitis (OR = 4.3, 95% CI = 1.7 to 11.1).
Conclusions Personal history of certain immune-related and/or infectious conditions was strongly associated with increased risk of LPL-WM. The association of both personal and family history of Sjögren syndrome and autoimmune hemolytic anemia with risk of LPL-WM indicates the potential for shared susceptibility for these conditions.
Introduction
Lymphoplasmacytic lymphoma (LPL)-Waldenström macroglobulinemia (WM) is a chronic lymphoproliferative tumor characterized by small B lymphocytes, plasmacytoid lymphocytes, and plasma cells and involves the bone marrow, lymph nodes, and spleen. The World Health Organization criteria for classification of hematological diseases list WM as a subset of LPL that is defined as LPL with bone marrow involvement and a detectable monoclonal IgM spike in serum. LPL-WM is a rare disease, with an annual incidence rate of three to four cases per million people. It is more common among the elderly, men, and white persons.
Although the etiology of LPL-WM is unknown, there are a few clues in the literature. For example, familial aggregation of WM was demonstrated in 1962. Since then, several studies of multiply affected families, case–control studies, and cohort studies have been published showing familial clustering of LPL and WM. Recently, we conducted a large population-based case–control study in Sweden and found that, compared with first-degree relatives of control subjects, first-degree relatives of LPL-WM patients have an increased risk for LPL-WM (odds ratio [OR] = 20, 95% confidence interval [CI] = 4.1 to 98.4), non-Hodgkin lymphoma (OR = 3.0, 95% CI = 2.0 to 4.4), chronic lymphocytic leukemia (OR = 3.4, 95% CI = 1.7 to 6.6), and monoclonal gammopathy of undetermined significance (OR = 5.0, 95% CI = 1.3 to 18.9). These findings support the hypothesis that there are shared common susceptibility genes that predispose individuals to LPL-WM and related lymphoproliferative disorders. Simultaneously, a few preclinical studies have reported evidence of somatic immunoglobulin gene mutations in WM, indicating a role for antigenic stimulation in the development of WM.
Because of the rarity of LPL-WM, only a few epidemiological studies have assessed the role of various types of chronic antigenic stimulatory conditions in relation to risk of developing LPL-WM, and their results have been conflicting. For example, a hospital-based study of 65 WM patients reported no association between a personal history of autoimmune disease and subsequent risk of developing WM. In contrast, two nationwide US veterans studies that included 361 and 165 WM patients, respectively, found increased risk of WM among individuals with a personal history of autoimmune disease, infection with hepatitis B and C virus or HIV, or rickettsiosis.
To increase understanding of the association between immune-related and/or inflammatory conditions and subsequent risk of LPL-WM, we conducted a large population-based case–control study by use of linked registry data from Sweden to examine the association between a personal history of various immune-related and/or inflammatory conditions and risk of LPL-WM. This study contained 2470 LPL-WM patients and 9698 matched control subjects. On the basis of previous observations that first-degree relatives of WM patients (compared with first-degree relatives of control subjects) might be more prone to developing various immunologic abnormalities and that immune and inflammatory genes might play a role in lymphomagenesis, we hypothesized that the association between immune-related and/or inflammatory conditions and risk of LPL-WM was modulated, to some degree, by polymorphisms in common genes that predisposed individuals to both types of conditions. If true, immune-related and/or inflammatory conditions and LPL-WM should aggregate in the same families. To test this hypothesis, we investigated 5710 first-degree relatives of case patients with LPL-WM and 22 799 first-degree relatives of control subjects to evaluate risk of LPL-WM among individuals with a family history of immune-related and/or inflammatory conditions.