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

Abstract

Various epidemiological studies, including case reports and -series in addition to larger, population-based studies, have reported an increased prevalence of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma in individuals with a prior history of immune-related conditions. This is believed to support the role of chronic antigen stimulation in the pathogenesis of these conditions. In this short review, we summarize some of the largest population-based studies researching autoimmune diseases, infections, and the subsequent risk of MGUS, and discuss our understanding on its etiology and pathogenesis. Furthermore, we highlight important methodological limitations of previous studies in the field, but almost all studies on MGUS have been based on clinical, possibly biased, cohorts. Finally, we discuss future directions in researching the associations of MGUS and other disorders, including immune-related conditions, where screening studies play an important role.

SARS‐CoV‐2 infection is not associated with the emergence of monoclonal gammopathies

“…Therefore, it appears that non‐respiratory viruses may interact directly with plasma cells and interfere with their growth and differentiation. In addition, respiratory tract infections have been suspected to be responsible for an increased risk of developing MGUS over time 10,16 …”

“…In addition, respiratory tract infections have been suspected to be responsible for an increased risk of developing MGUS over time. 10,16 During COVID-19 the "cytokine storm" (in particular, the secretion of IL-6) promotes the differentiation of B lymphocytes into plasma cells, that physiologically produce immunoglobulins. 24,26 In this view, our data show that there is no significant association between the development of MGUS and the respiratory virus SARS-CoV-2, both during the disease period and at short-term follow-up (3-12 months).…”

“…[10][11][12] In line with this, chronic antigen stimulation is a predisposing factor for the onset of MGUS and other B-cell disorders. [13][14][15][16][17] Indeed, infections could trigger plasma cell-transported IgH translocations (crucial for clonal proliferation), which are found in almost 50% of patients with MGUS. 18 For this reason, SPEP in patients with MC during a period of active infection requires monitoring to ascertain whether the observed MC is temporary.…”

The role of lymphoid tissue SPARC in the pathogenesis and response to treatment of multiple myeloma

“…Moreover, the myeloma monoclonal (M) Ig itself has autoantibody activity against several tissue antigens including collagen IV, phospholipase A2 receptor, collagen VII, myelin-associated glycoprotein, gangliosides, and lipoproteins, and by forming ICs and activating complement, it induces extensive tissue damage and cytokine secretion ( 71 ). Furthermore, autoimmune patients with detectable autoantibodies are at a significantly increased risk of MGUS than autoantibody-negative patients ( 72 , 73 ). Our results indicate that ICs in MM do not only induce tissue damage as previously reported but also regulate the ECM through induction of FDC–SPARC and modify the expression of several MM-associated oncogenes.…”

A rare case of schizophrenia coexistence with antiphospholipid syndrome, β-thalassemia, and monoclonal gammopathy of undetermined significance

“…Monoclonal gammopathy of undetermined significance (MGUS) is characterized by the presence of a monoclonal paraprotein in the blood, without the characteristic end organ damage seen in multiple myeloma. Numerous studies have found an increased incidence of MGUS in patients with autoimmune diseases, and their treatment may play an important role in the etiology of MGUS ( 27 , 28 ). However, the presence of monoclonal immunoglobulin and APS in the same patient is unusual.…”