Autoimmune disease is associated with a lower risk of progression in monoclonal gammopathy of undetermined significance

Abstract

Objectives and methods We conducted a population‐based study including 19 303 individuals diagnosed with MGUS in Sweden from 1985 to 2013, with the aim to determine whether a prior history of autoimmune disease, a well‐described risk factor for MGUS is a risk factor for progression of MGUS to multiple myeloma (MM) or lymphoproliferative diseases (LPs). Using the nationwide Swedish Patient registry, we identified MGUS cases with versus without an autoimmune disease present at the time of MGUS diagnosis and estimated their risk of progression. Results A total of 5612 (29.1%) MGUS cases had preceding autoimmune diseases. Using Cox proportional hazards models, we found the risk of progression from MGUS to MM (HR = 0.83, 95% CI 0.73‐0.94) and LPs (HR = 0.84, 95% CI 0.75‐0.94) to be significantly lower in MGUS cases with prior autoimmune disease (compared to MGUS cases without). Conclusions In this large population‐based study, a history of autoimmune disease was associated with a reduced risk of progression from MGUS to MM/other LPs. Potential underlying reason is that MGUS caused by chronic antigen stimulation is biologically less likely to undergo the genetic events that trigger progression. Our results may have implications in clinical counseling for patients with MGUS and underlying autoimmune disease.

Autoimmunity, Infections, and the Risk of Monoclonal Gammopathy of Undetermined Significance

“…This might suggest a biological difference of the MGUS found in individuals with a previous history of those conditions compared with those without. This is supported by the findings of Baldursdottir et al, who recently reported a lower risk of progression to MM in MGUS patients with preceding autoimmune diseases, compared with MGUS patients without such disorders ( 45 ).…”

Artificial intelligence-enabled screening strategy for drug repurposing in monoclonal gammopathy of undetermined significance

“…With respect to beta-blockers, a prior retrospective cohort study noted better outcomes among multiple myeloma patients on beta-blockers; similar results in MGUS patients have not previously been reported. Regarding thyroid supplementation, at least one population-based study, which included 19,303 patients with MGUS, noted a lower risk of disease progression in patients with autoimmune disease; the association between lower progression risk and the presence of thyroid supplementation may reflect this [16]. Overall, it is notable that, while associations between MGUS outcomes and metformin use appear to have been the most deeply explored in the literature to date [17][18][19], our primary analysis notes a stronger association with multivitamins immunosuppression, proton pump inhibitors, NSAIDS, Vitamin D supplementation, opioids, statins, and beta-blockers.…”

Editorial: The Role of Microorganisms in Multiple Myeloma

“…Many studies reported an increased prevalence of MGUS and MM in individuals with a prior history of auto-immunity or infections, supporting a role for chronic antigen stimulation in the pathogenesis of MGUS and MM ( 17 – 19 ). Sigurbergsdóttir et al.…”

“…methodological limitations of some studies, and the interest for prognosis and treatment of MGUS and MM of conducting further research on the association of auto-immune disease, infection and MGUS. Notably, a lower risk of progression to MM was found in MGUS patients with preceding autoimmune disease, compared with other patients (19). For MGUS and MM cases linked to HIV or HCV infection (20)(21)(22), the potential consequences for the therapy of MGUS (not treated presently) and MM are major: in pathogen-driven malignancies, when pathogen and antigen reduction or suppression is achieved, typically the associated malignancy is also reduced, or cured, including in MM (23)(24)(25).…”

“…Although MGUS is most often asymptomatic, patients may present with renal, neurological or skin symptoms of various severity (for instance, monoclonal gammopathies of renal significance (MGRS)) (6)(7)(8). Associations between MGUS and autoimmune disorders, infection and recently, gut microbiota, are established (3,5,9,10,(14)(15)(16)(17)(18)(19)(20)(21)(22). Importantly, several groups demonstrated that monoclonal Ig from MGUS and MM patients specifically target either a self-antigen (including myelin-associated glycoprotein (MAG), glucosylsphingosine (GlcSph, in 13-15% MGUS/MM cases), other gangliosides, different membrane components) or an antigen from an infectious pathogen (including HCV, HBV, HIV, EBV, other Herpesviruses, Helicobacter pylori, or Enteroviruses, in 60% MGUS and 33% MM).…”